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Abi Doumet A, Bustos B, Garrell J, Salman M, Haider L. Fibromuscular Dysplasia Presenting as Acute Unilateral Renal Infarction: A Case Report and Review of Two Diseases. Cureus 2023; 15:e35933. [PMID: 37038580 PMCID: PMC10082588 DOI: 10.7759/cureus.35933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/09/2023] [Indexed: 03/11/2023] Open
Abstract
Fibromuscular dysplasia (FMD) is a rare systemic vascular disease that has been found to present as a renal infarction (RI) in only a handful of cases. We present a case of a 53-year-old Vietnamese patient presenting for sharp, severe left-sided abdominal pain of two-day duration associated with a migraine headache. On presentation, she was afebrile, and her vital signs were stable. Laboratory investigations were significant for mildly elevated leukocytosis but were otherwise normal. CT abdomen and pelvis with contrast revealed a left-sided renal infarct. The patient was then admitted to the hospital and started on therapeutic anticoagulation. A transthoracic echocardiogram was obtained and revealed no vegetation. CT angiography of the abdomen was pursued and was significant for mild beading within the mid-right and left renal arteries, consistent with fibromuscular dysplasia. Our patient was diagnosed with renal infarction in the setting of fibromuscular dysplasia, a combination that has been reported only a few times. Interestingly, our patient also had mild FMD based on imaging, making it even more of an unusual cause of renal infarction. This case highlights the connection between these two diseases and the need for more studies to characterize the association between them.
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2
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Mehkri Y, Poe J, Murshid M, Hernandez J, Singh P, Sinha VN, Shuhaiber H. Retinal Artery Occlusion in Fibromuscular Dysplasia: A Case Report. Cureus 2022; 14:e31462. [DOI: 10.7759/cureus.31462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/13/2022] [Indexed: 11/15/2022] Open
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3
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Adenosine Receptors Profile in Fibromuscular Dysplasia. Biomedicines 2022; 10:biomedicines10112831. [PMID: 36359350 PMCID: PMC9687922 DOI: 10.3390/biomedicines10112831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 10/19/2022] [Accepted: 11/02/2022] [Indexed: 11/09/2022] Open
Abstract
Fibromuscular dysplasia (FMD) is a non-inflammatory vascular disease that is characterized by unexplained systemic hypertension occurring in young people, associated with arterial stenosis, aneurysm rupture, intracranial/renal infarction, and stroke. Although the gold standard for the diagnosis remains catheter-angiography, biological markers would be helpful due to the delay from first symptom to diagnosis. Adenosine is an ATP derivative, that may be implicated in FMD pathophysiology. We hypothesized that changes in adenosine blood level (ABL) and production of adenosine receptors may be associated with FMD. Using peripheral blood mononuclear cells, we evaluated A1, A2A, and A2B receptor production by Western blot, in 67 patients (17 men and 50 women, mean (range) age 55 (29−77) years and 40 controls, 10 men and 30 women, mean (range) age 56 (37−70)). ABL was evaluated by liquid chromatography, mass spectrometry. ABL was significantly higher in patients vs. controls, mean (range): 1.7 (0.7−3) µmol/L vs. controls 0.6 (0.4−0.8) µmol/L (+180%) p < 0.001. While A1R and A2AR production did not differ in patients and controls, we found an over-production of A2BR in patients: 1.70 (0.90−2.40; arbitrary units) vs. controls = 1.03 (0.70−1.40), mean + 65% (p < 0.001). A2BR production with a cut off of 1.3 arbitrary units, gives a good sensitivity and specificity for the diagnosis. Production measurement of A2BR on monocytes and ABL could help in the diagnosis, especially in atypical or with poor symptoms.
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4
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Tarsia J, Vidal G, Zweifler RM. Arterial Dissection, Fibromuscular Dysplasia, and Carotid Webs. Stroke 2022. [DOI: 10.1016/b978-0-323-69424-7.00035-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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5
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Early Graft Failure after Coronary Artery Bypass Surgery: A Case of Anastomosis Detachment Due to Fibromuscular Dysplasia. HEARTS 2021. [DOI: 10.3390/hearts2030030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory arteriopathy, considered a rare cause of coronary artery disease. Although familial cases have been described, no specific gene association has been detected so far. When the coronary vessels are involved, the main clinical scenarios are stable angina, acute coronary syndromes, left ventricular dysfunction, and sudden death. Specific clinical and angiographic findings may suggest this as the underlying disease, but certain diagnosis histological. The involvement of the lower and upper limbs is unusual; however, it may have decisive clinical implications for the most appropriate revascularization method and the selection of the arterial graft to be used.
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6
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Donner I, Sipilä LJ, Plaketti RM, Kuosmanen A, Forsström L, Katainen R, Kuismin O, Aavikko M, Romsi P, Kariniemi J, Aaltonen LA. Next-generation sequencing in a large pedigree segregating visceral artery aneurysms suggests potential role of COL4A1/COL4A2 in disease etiology. Vascular 2021; 30:842-847. [PMID: 34281442 DOI: 10.1177/17085381211033157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Visceral artery aneurysms (VAAs) can be fatal if ruptured. Although a relatively rare incident, it holds a contemporary mortality rate of approximately 12%. VAAs have multiple possible causes, one of which is genetic predisposition. Here, we present a striking family with seven individuals affected by VAAs, and one individual affected by a visceral artery pseudoaneurysm. METHODS We exome sequenced the affected family members and the parents of the proband to find a possible underlying genetic defect. As exome sequencing did not reveal any feasible protein-coding variants, we combined whole-genome sequencing of two individuals with linkage analysis to find a plausible non-coding culprit variant. Variants were ranked by the deep learning framework DeepSEA. RESULTS Two of seven top-ranking variants, NC_000013.11:g.108154659C>T and NC_000013.11:g.110409638C>T, were found in all VAA-affected individuals, but not in the individual affected by the pseudoaneurysm. The second variant is in a candidate cis-regulatory element in the fourth intron of COL4A2, proximal to COL4A1. CONCLUSIONS As type IV collagens are essential for the stability and integrity of the vascular basement membrane and involved in vascular disease, we conclude that COL4A1 and COL4A2 are strong candidates for VAA susceptibility genes.
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Affiliation(s)
- Iikki Donner
- Department of Medical and Clinical Genetics, Medicum, 3835University of Helsinki, Helsinki, Finland.,Genome-Scale Biology Research Program, Research Programs Unit, 3835University of Helsinki, Helsinki, Finland
| | - Lauri J Sipilä
- Department of Medical and Clinical Genetics, Medicum, 3835University of Helsinki, Helsinki, Finland.,Genome-Scale Biology Research Program, Research Programs Unit, 3835University of Helsinki, Helsinki, Finland
| | - Roosa-Maria Plaketti
- Department of Medical and Clinical Genetics, Medicum, 3835University of Helsinki, Helsinki, Finland.,Genome-Scale Biology Research Program, Research Programs Unit, 3835University of Helsinki, Helsinki, Finland
| | - Anna Kuosmanen
- Department of Medical and Clinical Genetics, Medicum, 3835University of Helsinki, Helsinki, Finland.,Genome-Scale Biology Research Program, Research Programs Unit, 3835University of Helsinki, Helsinki, Finland
| | - Linda Forsström
- Department of Medical and Clinical Genetics, Medicum, 3835University of Helsinki, Helsinki, Finland.,Genome-Scale Biology Research Program, Research Programs Unit, 3835University of Helsinki, Helsinki, Finland
| | - Riku Katainen
- Department of Medical and Clinical Genetics, Medicum, 3835University of Helsinki, Helsinki, Finland.,Genome-Scale Biology Research Program, Research Programs Unit, 3835University of Helsinki, Helsinki, Finland
| | - Outi Kuismin
- Department of Clinical Genetics, 60664Oulu University Hospital, Oulu, Finland.,PEDEGO Research Unit, Medical Research Center Oulu, 60664Oulu University Hospitaland University of Oulu, Oulu, Finland
| | - Mervi Aavikko
- Department of Medical and Clinical Genetics, Medicum, 3835University of Helsinki, Helsinki, Finland.,Genome-Scale Biology Research Program, Research Programs Unit, 3835University of Helsinki, Helsinki, Finland.,Institute for Molecular Medicine Finland (FIMM), HiLIFE, 3835University of Helsinki, Helsinki, Finland
| | - Pekka Romsi
- Department of Vascular Surgery, 60664Oulu University Hospital, Oulu, Finland
| | - Juho Kariniemi
- Department of Radiology, 60664Oulu University Hospital, Oulu, Finland
| | - Lauri A Aaltonen
- Department of Medical and Clinical Genetics, Medicum, 3835University of Helsinki, Helsinki, Finland.,Genome-Scale Biology Research Program, Research Programs Unit, 3835University of Helsinki, Helsinki, Finland
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7
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Oribe S, Toyohara T, Mishima E, Suzuki T, Kikuchi K, Watanabe S, Morita Y, Ota H, Seiji K, Miyazaki M, Takase K, Abe T. Fibromuscular dysplasia with recurrence after "long-term" following percutaneous transcatheter renal angioplasty: two case reports with a review of 26 patients. BMC Nephrol 2021; 22:187. [PMID: 34016044 PMCID: PMC8135181 DOI: 10.1186/s12882-021-02342-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 04/08/2021] [Indexed: 11/25/2022] Open
Abstract
Background Fibromuscular dysplasia (FMD) often causes renal artery stenosis with renovascular hypertension. Recent clinical outcomes encourage percutaneous transluminal renal angioplasty (PTRA) to treat FMD; however, the necessary follow-up period remains unclear. Moreover, previous studies have not revealed the difference in the period until recurrence between two major types of FMD—multifocal and focal. Case presentation We describe two patients with multifocal FMD who developed hypertension during their teenage years and had recurrence of FMD > 10 years after PTRA. We further examined the types of FMD and age of onset in 26 patients who underwent PTRA. The period until recurrence of multifocal FMD was longer than that of focal FMD. Moreover, patients with early-onset multifocal FMD are likely to have a delayed recurrence after PTRA compared to other types. Conclusions Our report suggests that patients with multifocal FMD, especially those with onset at an early age, may need long-term follow-up for at least ≥ 10 years.
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Affiliation(s)
- Shuntaro Oribe
- Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takafumi Toyohara
- Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.,Division of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan
| | - Eikan Mishima
- Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takehiro Suzuki
- Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.,Division of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan
| | - Koichi Kikuchi
- Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Shun Watanabe
- Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yoshiaki Morita
- Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hideki Ota
- Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kazumasa Seiji
- Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Mariko Miyazaki
- Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kei Takase
- Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takaaki Abe
- Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. .,Division of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan. .,Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine, 980-8574, Sendai, Japan.
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8
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Chromosome 1q21.2 and additional loci influence risk of spontaneous coronary artery dissection and myocardial infarction. Nat Commun 2020; 11:4432. [PMID: 32887874 PMCID: PMC7474092 DOI: 10.1038/s41467-020-17558-x] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Accepted: 06/26/2020] [Indexed: 01/06/2023] Open
Abstract
Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic cause of myocardial infarction (MI), typically in young women. We undertook a genome-wide association study of SCAD (Ncases = 270/Ncontrols = 5,263) and identified and replicated an association of rs12740679 at chromosome 1q21.2 (Pdiscovery+replication = 2.19 × 10−12, OR = 1.8) influencing ADAMTSL4 expression. Meta-analysis of discovery and replication samples identified associations with P < 5 × 10−8 at chromosome 6p24.1 in PHACTR1, chromosome 12q13.3 in LRP1, and in females-only, at chromosome 21q22.11 near LINC00310. A polygenic risk score for SCAD was associated with (1) higher risk of SCAD in individuals with fibromuscular dysplasia (P = 0.021, OR = 1.82 [95% CI: 1.09–3.02]) and (2) lower risk of atherosclerotic coronary artery disease and MI in the UK Biobank (P = 1.28 × 10−17, HR = 0.91 [95% CI :0.89–0.93], for MI) and Million Veteran Program (P = 9.33 × 10−36, OR = 0.95 [95% CI: 0.94–0.96], for CAD; P = 3.35 × 10−6, OR = 0.96 [95% CI: 0.95–0.98] for MI). Here we report that SCAD-related MI and atherosclerotic MI exist at opposite ends of a genetic risk spectrum, inciting MI with disparate underlying vascular biology. Spontaneous coronary artery dissection (SCAD) is a cause of myocardial infarction Here, the authors present a genome-wide association study of SCAD, finding an association at 1q21.2 which potentially affects expression of ADAMTSL4.
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9
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McDonald A. A Case of Isolated Intracranial Fibromuscular Dysplasia. Cureus 2020; 12:e8755. [PMID: 32714693 PMCID: PMC7377658 DOI: 10.7759/cureus.8755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Fibromuscular dysplasia (FMD) is a non-inflammatory, non-atherosclerotic disease resulting in stenosis and arterial wall weakening of typically medium-sized arteries. Intracranial aneurysm is an uncommon presentation of FMD, with a significant proportion presenting in the posterior circulation. Presented is the rare case of an adult female with left-sided stroke with angiographically-confirmed left middle cerebral artery FMD, with pan-scanning unremarkable for other demonstrable evidence of FMD. The patient's neurological deficits completely resolved. The patient was stable for discharge home on antiplatelet therapy. Appropriate imaging and screening should be performed to ensure FMD is localized versus systemic. Patients with intracranial FMD should be protected from cerebrovascular events with antiplatelet therapy.
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Affiliation(s)
- Abigail McDonald
- Internal Medicine, Hospital Corporation of America Healthcare in Association with the University of South Florida Morsani College of Medicine Graduate Medical Education Programs, Northside Hospital, St. Petersburg, USA
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10
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Progesterone receptor expression in fibromuscular dysplasia: A report of two unusual cases. TURK GOGUS KALP DAMAR CERRAHISI DERGISI-TURKISH JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2019; 27:234-240. [PMID: 32082860 DOI: 10.5606/tgkdc.dergisi.2019.15051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 01/20/2019] [Indexed: 11/21/2022]
Abstract
Fibromuscular dysplasia is rarely biopsied. Progesterone receptor expression in myofibroblastic cells is useful for the histopathological evaluation in difficult-to-diagnose cases. Herein, we report two unusual cases of fibromuscular dysplasia in which progesterone receptor expression was shown in vessel sections.
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11
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Chothia MY, Davids MR, Bhikoo R. Awakening the sleeping kidney in a dialysis-dependent patient with fibromuscular dysplasia: A case report and review of literature. World J Nephrol 2018; 7:143-147. [PMID: 30510913 PMCID: PMC6259034 DOI: 10.5527/wjn.v7.i7.143] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 09/06/2018] [Accepted: 10/10/2018] [Indexed: 02/06/2023] Open
Abstract
Renal artery stenosis is a common cause of secondary hypertension and chronic kidney disease. We present here a case of fibromuscular dysplasia that was treated with surgical revascularization, resulting in recovery of kidney function with eventual cessation of chronic dialysis. The case involves a 25-year-old female with coincidentally discovered hypertension, who underwent further investigations revealing a diagnosis of renal artery stenosis due to fibromuscular dysplasia. She subsequently developed two episodes of malignant hypertension, with flash pulmonary oedema and worsening renal failure that resulted in dialysis dependence. After evidence was obtained that the right kidney was still viable, a revascularization procedure was performed, improving blood pressure control and restoring kidney function, thereby allowing dialysis to be stopped. This case highlights the importance of evaluating patients with renal artery stenosis for revascularization before committing them to a life of chronic dialysis.
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Affiliation(s)
- Mogamat-Yazied Chothia
- Renal Unit, Tygerberg Hospital, Cape Town 7505, South Africa
- Division of Nephrology, Department of Medicine, Tygerberg Hospital and Stellenbosch University, Cape Town 7505, South Africa
| | - Mogamat Razeen Davids
- Division of Nephrology, Department of Medicine, Tygerberg Hospital and Stellenbosch University, Cape Town 7505, South Africa
| | - Raisa Bhikoo
- Division of Nephrology, Department of Medicine, Tygerberg Hospital and Stellenbosch University, Cape Town 7505, South Africa
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12
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Van der Niepen P, van Tussenbroek F, Devos H, Debing E, Di Monaco S, Goffette P, Astarci P, Persu A. Visceral Fibromuscular Dysplasia: From asymptomatic disorder to emergency. Eur J Clin Invest 2018; 48:e13023. [PMID: 30156710 DOI: 10.1111/eci.13023] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 08/16/2018] [Accepted: 08/24/2018] [Indexed: 12/24/2022]
Abstract
Fibromuscular dysplasia (FMD) is an idiopathic, segmental, non-atherosclerotic and non-inflammatory disease of the musculature of arterial walls, leading to stenosis of small and medium-sized arteries, mostly involving renal and cervical arteries. As a result of better and more systematic screening, it appears that involvement of the splanchnic vascular bed is more frequent than originally assumed. We review epidemiology, pathogenesis, clinical picture as well as diagnosis and treatment of visceral artery (VA) FMD. The clinical picture is very diverse, and diagnosis is based on CT-, MR- or conventional catheter-based angiography. Involvement of VAs generally occurs among patients with multi-vessel FMD. Therefore, screening for VA FMD is advised especially in renal artery (RA) FMD and in case of aneurysms and/or dissections. Treatment depends on the clinical picture. However, the level of evidence is low, and much of the common practice is extrapolated from visceral atherosclerotic disease.
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Affiliation(s)
- Patricia Van der Niepen
- Department of Nephrology & Hypertension, Universitair Ziekenhuis Brussel. Vrije Universiteit Brussel, Brussels, Belgium
| | - Frank van Tussenbroek
- Department of Radiology, Universitair Ziekenhuis Brussel. Vrije Universiteit Brussel, Brussels, Belgium
| | - Hannes Devos
- Department of Radiology, Universitair Ziekenhuis Brussel. Vrije Universiteit Brussel, Brussels, Belgium
| | - Erik Debing
- Department of Vascular Surgery, Universitair Ziekenhuis Brussel. Vrije Universiteit Brussel, Brussels, Belgium
| | - Silvia Di Monaco
- Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.,Internal Medicine and Hypertension Division, Department of Medical Sciences, AOU Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Pierre Goffette
- Department of Radiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Parla Astarci
- Division of Vascular Surgery, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.,Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Alexandre Persu
- Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.,Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
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13
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Di Monaco S, Georges A, Lengelé JP, Vikkula M, Persu A. Genomics of Fibromuscular Dysplasia. Int J Mol Sci 2018; 19:ijms19051526. [PMID: 29883369 PMCID: PMC5983654 DOI: 10.3390/ijms19051526] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 05/16/2018] [Accepted: 05/16/2018] [Indexed: 01/09/2023] Open
Abstract
Fibromuscular Dysplasia (FMD) is “an idiopathic, segmental, non-atherosclerotic and non-inflammatory disease of the musculature of arterial walls, leading to stenosis of small and medium-sized arteries” (Persu, et al; 2014). FMD can lead to hypertension, arterial dissections, subarachnoid haemorrhage, stroke or mesenteric ischemia. The pathophysiology of the disease remains elusive. While familial cases are rare (<5%) in contemporary FMD registries, there is evidence in favour of the existence of multiple genetic factors involved in this vascular disease. Recent collaborative efforts allowed the identification of a first genetic locus associated with FMD. This intronic variant located in the phosphatase and actin regulator 1 gene (PHACTR1) may influence the transcription activity of the endothelin-1 gene (EDN1) located nearby on chromosome 6. Interestingly, the PHACTR1 locus has also been involved in vascular hypertrophy in normal subjects, carotid dissection, migraine and coronary artery disease. National and international registries of FMD patients, with deep and harmonised phenotypic and genetic characterisation, are expected to be instrumental to improve our understanding of the genetic basis and pathophysiology of this intriguing vascular disease.
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Affiliation(s)
- Silvia Di Monaco
- Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium.
- Department of Medical Sciences, Internal Medicine and Hypertension Division, AOU Città della Salute e della Scienza, University of Turin, 10124 Turin, Italy.
| | - Adrien Georges
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), F-75015 Paris, France.
| | - Jean-Philippe Lengelé
- Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium.
- Department of Nephrology, Grand Hôpital De Charleroi, 6060 Gilly, Belgium.
| | - Miikka Vikkula
- Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, 1200 Brussels, Belgium.
| | - Alexandre Persu
- Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium.
- Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, 1200 Brussels, Belgium.
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14
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Abstract
OPINION STATEMENT Takayasu arteritis, fibromuscular dysplasia (FMD), spontaneous arterial dissection, Raynaud's phenomenon, and chilblains are vascular conditions that are associated with an increased predisposition in women and are often underdiagnosed. Takayasu arteritis has an incidence rate of 2.6 cases per million individuals per year in the USA and predominantly affects women of childbearing age. HLA-B5 genetic locus is linked with Takayasu arteritis susceptibility. Methods to determine active disease are limiting; currently utilized clinical and imaging findings and laboratory tests are of limited value for this purpose. Pregnancy poses risks for maternal and fetal complications, and these patients need additional monitoring and care before and after conception. Controlling hypertension and immunosuppression using steroids, biological and non-biological immunosuppressants, are key components of managing patients with this arteritis. FMD commonly affects middle-aged, white females. Its true prevalence is unknown. Renal and cerebrovascular beds are the most frequently involved vascular beds. Its clinical presentation varies from no symptoms to catastrophic events. Controlling vascular risk factors, periodic surveillance, and revascularization when indicated are important factors in FMD management. Spontaneous arterial dissections are less common, but are an important cause of morbidity and mortality in specific populations. Cervicocephalic dissection causes 10-20% of the strokes in young adults, and coronary artery dissection is the culprit in almost one fourth of young women presenting with acute myocardial infarction. Early diagnosis is key to improving prognosis in these patients, as the majority of patients have spontaneous resolution of the dissection with conservative management alone. Increased clinician awareness of the presentation features and angiographic findings are imperative for early diagnosis. Raynaud's phenomenon and chilblains are cold- or stress-induced cutaneous lesions, commonly involving distal extremities. Secondary causes such as connective tissue diseases and malignancies must be thoroughly excluded during evaluation of these conditions. Cold avoidance, systemic and local warming, and oral vasodilator therapy are the mainstays of therapy.
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15
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Plouin PF, Baguet JP, Thony F, Ormezzano O, Azarine A, Silhol F, Oppenheim C, Bouhanick B, Boyer L, Persu A, Hammer F, Gosse P, Mounier-Vehier C, Le Hello C, Jeunemaitre X, Azizi M, Amar L, Chatellier G, Mousseaux E, Touzé; E. High Prevalence of Multiple Arterial Bed Lesions in Patients With Fibromuscular Dysplasia. Hypertension 2017; 70:652-658. [DOI: 10.1161/hypertensionaha.117.09539] [Citation(s) in RCA: 88] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 04/23/2017] [Accepted: 05/12/2017] [Indexed: 12/16/2022]
Affiliation(s)
- Pierre-François Plouin
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Jean-Philippe Baguet
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Frédéric Thony
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Olivier Ormezzano
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Arshid Azarine
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - François Silhol
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Catherine Oppenheim
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Béatrice Bouhanick
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Louis Boyer
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Alexandre Persu
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Frank Hammer
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Philippe Gosse
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Claire Mounier-Vehier
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Claire Le Hello
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Xavier Jeunemaitre
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Michel Azizi
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Laurence Amar
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Gilles Chatellier
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Elie Mousseaux
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
| | - Emmanuel Touzé;
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit (P.-F.P., M.A., L.A.); Department of Radiology (A.A., E.M.), Department of Genetics (X.J.), and Department of Clinical Epidemiology (G.C.); INSERM CIC1418, Paris (M.A., G.C.); Department of Neurology (C.O.) and INSERM U894, Hôpital Sainte-Anne (C.O.), Paris; Faculté de Médecine, Université Paris-Descartes (P.-F.P., M.A., L.A., A.A., E.M., X.J., G.C., C.O.); Department of Cardiology, CHU de Grenoble (J.-P.B.,
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Guo DC, Duan XY, Regalado ES, Mellor-Crummey L, Kwartler CS, Kim D, Lieberman K, de Vries BB, Pfundt R, Schinzel A, Kotzot D, Shen X, Yang ML, Bamshad MJ, Nickerson DA, Gornik HL, Ganesh SK, Braverman AC, Grange DK, Milewicz DM, Milewicz DM. Loss-of-Function Mutations in YY1AP1 Lead to Grange Syndrome and a Fibromuscular Dysplasia-Like Vascular Disease. Am J Hum Genet 2017; 100:21-30. [PMID: 27939641 DOI: 10.1016/j.ajhg.2016.11.008] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 11/04/2016] [Indexed: 12/27/2022] Open
Abstract
Fibromuscular dysplasia (FMD) is a heterogeneous group of non-atherosclerotic and non-inflammatory arterial diseases that primarily involves the renal and cerebrovascular arteries. Grange syndrome is an autosomal-recessive condition characterized by severe and early-onset vascular disease similar to FMD and variable penetrance of brachydactyly, syndactyly, bone fragility, and learning disabilities. Exome-sequencing analysis of DNA from three affected siblings with Grange syndrome identified compound heterozygous nonsense variants in YY1AP1, and homozygous nonsense or frameshift YY1AP1 variants were subsequently identified in additional unrelated probands with Grange syndrome. YY1AP1 encodes yin yang 1 (YY1)-associated protein 1 and is an activator of the YY1 transcription factor. We determined that YY1AP1 localizes to the nucleus and is a component of the INO80 chromatin remodeling complex, which is responsible for transcriptional regulation, DNA repair, and replication. Molecular studies revealed that loss of YY1AP1 in vascular smooth muscle cells leads to cell cycle arrest with decreased proliferation and increased levels of the cell cycle regulator p21/WAF/CDKN1A and disrupts TGF-β-driven differentiation of smooth muscle cells. Identification of YY1AP1 mutations as a cause of FMD indicates that this condition can result from underlying genetic variants that significantly alter the phenotype of vascular smooth muscle cells.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Dianna M Milewicz
- Department of Internal Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, USA.
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Kanwar SS, Hayes SN, Olson TM, Gulati R. A breakthrough in spontaneous coronary artery dissection pathogenesis: is it an inherited condition? Expert Rev Cardiovasc Ther 2017; 15:1-2. [DOI: 10.1080/14779072.2017.1266254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Siddak S. Kanwar
- College of Agriculture and Life Sciences, University of Wisconsin-Madison, Madison, WI, USA
| | - Sharonne N. Hayes
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester MN, USA
| | - Timothy M. Olson
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester MN, USA
| | - Rajiv Gulati
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester MN, USA
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Kiando SR, Tucker NR, Castro-Vega LJ, Katz A, D’Escamard V, Tréard C, Fraher D, Albuisson J, Kadian-Dodov D, Ye Z, Austin E, Yang ML, Hunker K, Barlassina C, Cusi D, Galan P, Empana JP, Jouven X, Gimenez-Roqueplo AP, Bruneval P, Hyun Kim ES, Olin JW, Gornik HL, Azizi M, Plouin PF, Ellinor PT, Kullo IJ, Milan DJ, Ganesh SK, Boutouyrie P, Kovacic JC, Jeunemaitre X, Bouatia-Naji N. PHACTR1 Is a Genetic Susceptibility Locus for Fibromuscular Dysplasia Supporting Its Complex Genetic Pattern of Inheritance. PLoS Genet 2016; 12:e1006367. [PMID: 27792790 PMCID: PMC5085032 DOI: 10.1371/journal.pgen.1006367] [Citation(s) in RCA: 133] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Accepted: 09/16/2016] [Indexed: 12/31/2022] Open
Abstract
Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, dissection and aneurysm affecting mainly the renal and cerebrovascular arteries. FMD is often an underdiagnosed cause of hypertension and stroke, has higher prevalence in females (~80%) but its pathophysiology is unclear. We analyzed ~26K common variants (MAF>0.05) generated by exome-chip arrays in 249 FMD patients and 689 controls. We replicated 13 loci (P<10-4) in 402 cases and 2,537 controls and confirmed an association between FMD and a variant in the phosphatase and actin regulator 1 gene (PHACTR1). Three additional case control cohorts including 512 cases and 669 replicated this result and overall reached the genomic level of significance (OR = 1.39, P = 7.4×10-10, 1,154 cases and 3,895 controls). The top variant, rs9349379, is intronic to PHACTR1, a risk locus for coronary artery disease, migraine, and cervical artery dissection. The analyses of geometrical parameters of carotids from ~2,500 healthy volunteers indicate higher intima media thickness (P = 1.97×10-4) and wall to lumen ratio (P = 0.002) in rs9349379-A carriers, suggesting indices of carotid hypertrophy previously described in carotids of FMD patients. Immunohistochemistry detected PHACTR1 in endothelium and smooth muscle cells of FMD and normal human carotids. The expression of PHACTR1 by genotypes in primary human fibroblasts showed higher expression in rs9349379-A carriers (N = 86, P = 0.003). Phactr1 knockdown in zebrafish resulted in dilated vessels indicating subtle impaired vascular development. We report the first susceptibility locus for FMD and provide evidence for a complex genetic pattern of inheritance and indices of shared pathophysiology between FMD and other cardiovascular and neurovascular diseases.
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Affiliation(s)
- Soto Romuald Kiando
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
| | - Nathan R. Tucker
- Cardiovascular research Center, Massachusetts General Hospital, Charlestown, MA 02114, USA, Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA 02142
| | - Luis-Jaime Castro-Vega
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
| | - Alexander Katz
- Department of Internal Medicine and Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
| | - Valentina D’Escamard
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine, Marie-Josée and Henry R. Kravis Cardiovascular Health Center at Mount Sinai, One Gustave L. Levy Place, Box 1030 New York, NY 10029, New York, NY, USA
| | - Cyrielle Tréard
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
| | - Daniel Fraher
- Cardiovascular research Center, Massachusetts General Hospital, Charlestown, MA 02114, USA, Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA 02142
| | - Juliette Albuisson
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
- Assistance Publique-Hôpitaux De Paris, Referral Center for Rare Vascular Diseases, Hôpital Européen Georges Pompidou, Paris, F-75015, FRANCE
- Assistance Publique-Hôpitaux De Paris, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, F-75015, FRANCE
| | - Daniella Kadian-Dodov
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine, Marie-Josée and Henry R. Kravis Cardiovascular Health Center at Mount Sinai, One Gustave L. Levy Place, Box 1030 New York, NY 10029, New York, NY, USA
| | - Zi Ye
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA
| | - Erin Austin
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA
| | - Min-Lee Yang
- Department of Internal Medicine and Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
| | - Kristina Hunker
- Department of Internal Medicine and Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
| | - Cristina Barlassina
- Dept. of Health Sciences, Genomic and Bioinformatics Unit, Viale Ortles 22/4, Milano, Chair and Graduate School of Nephrology, University of Milano, Division of Nephrology, San Paolo Hospital, Milano, 20142,ITALY
| | - Daniele Cusi
- Institute of Biomedical Technologies, Italian National Centre of Research, Via F.lli Cervi 93, 20090 Segrate - Milano
| | - Pilar Galan
- Nutritional Epidemiology Research Group, Sorbonne-Paris-Cité, UMR University of Paris 13/Inserm U-557/INRA U-1125/CNAM, Bobigny, France F-93017, Bobigny, FRANCE
| | - Jean-Philippe Empana
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
| | - Xavier Jouven
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
- Assistance Publique-Hôpitaux De Paris, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, F-75015, FRANCE
| | - Anne-Paule Gimenez-Roqueplo
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
- Assistance Publique-Hôpitaux De Paris, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, F-75015, FRANCE
| | - Patrick Bruneval
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
| | - Esther Soo Hyun Kim
- Department of Cardiovascular Medicine, Cleveland Clinic Heart and Vascular Institute, Cleveland, OH 44195, USA
| | - Jeffrey W. Olin
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine, Marie-Josée and Henry R. Kravis Cardiovascular Health Center at Mount Sinai, One Gustave L. Levy Place, Box 1030 New York, NY 10029, New York, NY, USA
| | - Heather L. Gornik
- Department of Cardiovascular Medicine, Cleveland Clinic Heart and Vascular Institute, Cleveland, OH 44195, USA
| | - Michel Azizi
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
- Assistance Publique-Hôpitaux De Paris, Department of Hypertension, Hôpital Européen Georges Pompidou, Paris, F-75015, FRANCE
- INSERM, Clinical Investigation Center CIC1418, Hôpital Européen Georges Pompidou, Paris, F-75015, FRANCE
| | - Pierre-François Plouin
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
- Assistance Publique-Hôpitaux De Paris, Department of Hypertension, Hôpital Européen Georges Pompidou, Paris, F-75015, FRANCE
| | - Patrick T. Ellinor
- Cardiovascular research Center, Massachusetts General Hospital, Charlestown, MA 02114, USA, Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA 02142
| | - Iftikhar J. Kullo
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA
| | - David J. Milan
- Cardiovascular research Center, Massachusetts General Hospital, Charlestown, MA 02114, USA, Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA 02142
| | - Santhi K. Ganesh
- Department of Internal Medicine and Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
| | - Pierre Boutouyrie
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
- Assistance Publique-Hôpitaux De Paris, Department of Pharmacology, Hôpital Européen Georges Pompidou, Paris, F-75015, FRANCE
| | - Jason C. Kovacic
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine, Marie-Josée and Henry R. Kravis Cardiovascular Health Center at Mount Sinai, One Gustave L. Levy Place, Box 1030 New York, NY 10029, New York, NY, USA
| | - Xavier Jeunemaitre
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
- Assistance Publique-Hôpitaux De Paris, Referral Center for Rare Vascular Diseases, Hôpital Européen Georges Pompidou, Paris, F-75015, FRANCE
- Assistance Publique-Hôpitaux De Paris, Department of Genetics, Hôpital Européen Georges Pompidou, Paris, F-75015, FRANCE
| | - Nabila Bouatia-Naji
- INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE
- Paris-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE
- * E-mail:
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Lewis S, Kadian-Dodov D, Bansal A, Lookstein RA. Multimodality imaging of fibromuscular dysplasia. Abdom Radiol (NY) 2016; 41:2048-60. [PMID: 27216744 DOI: 10.1007/s00261-016-0778-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Fibromuscular dysplasia (FMD) is an uncommon non-inflammatory and non-atherosclerotic cause of arterial disease that may result in stenosis, tortuosity, aneurysm, or dissection. The clinical presentation depends on the vascular bed involved and ranges from asymptomatic to multisystem disease and end organ ischemia. The purpose of this article is to review the role of imaging in patients with FMD with an emphasis on renal FMD. The relevant epidemiology, histopathology, imaging techniques, and interpretation of images will be discussed. CONCLUSION Renal artery FMD requires a high index of suspicion for accurate and prompt diagnosis and implementation of appropriate therapy. The treatment will vary based on clinical presentation and distribution of involvement. Noninvasive imaging with duplex ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are reasonable alternatives for the depiction of FMD in comparison to catheter-directed angiography (CA). Patients with FMD are often treated by multispecialty practice including the interventional radiologist.
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Affiliation(s)
- Sara Lewis
- Body Imaging Section, Department of Radiology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA.
| | - Daniella Kadian-Dodov
- Division of Cardiology, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA
| | - A Bansal
- Body Imaging Section, Department of Radiology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA
| | - R A Lookstein
- Division of Interventional Radiology, Department of Radiology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA
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21
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Persu A, Van der Niepen P, Touzé E, Gevaert S, Berra E, Mace P, Plouin PF, Jeunemaitre X. Revisiting Fibromuscular Dysplasia: Rationale of the European Fibromuscular Dysplasia Initiative. Hypertension 2016; 68:832-9. [PMID: 27504007 DOI: 10.1161/hypertensionaha.116.07543] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- Alexandre Persu
- From the Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique (A.P., E.B.), and Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. (A.P.); Department of Internal Medicine, Division of Nephrology and Hypertension, Universitair Ziekenhuis Brussel (Vrije Universiteit Brussel, VUB), Brussel, Belgium, (P.V.D.N.); Normandie Université, UNICAEN, Inserm U919, CHU Côte de Nacre, Caen, 14000 France (E.T.); Department of Cardiology, Ghent University Hospital, Ghent, Belgium (S.G.); Department of Medical Sciences, Internal Medicine and Hypertension Division, AOU Città della Salute e della Scienza, Turin, Italy (E.B.); Fibromuscular Dysplasia Society of America, Rocky River, OH (P.M.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, F-75015 Paris, France (P.-F.P.); Université Paris-Descartes, Paris Sorbonne Cité, F-75006 Paris, France (P.-F.P.); and Université Paris-Descartes, Paris Sorbonne Cité; AP-HP, Department of Genetics, Hôpital Europeen Georges Pompidou; INSERM, UMR-S 970, PARCC, Paris, France (X.J.).
| | - Patricia Van der Niepen
- From the Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique (A.P., E.B.), and Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. (A.P.); Department of Internal Medicine, Division of Nephrology and Hypertension, Universitair Ziekenhuis Brussel (Vrije Universiteit Brussel, VUB), Brussel, Belgium, (P.V.D.N.); Normandie Université, UNICAEN, Inserm U919, CHU Côte de Nacre, Caen, 14000 France (E.T.); Department of Cardiology, Ghent University Hospital, Ghent, Belgium (S.G.); Department of Medical Sciences, Internal Medicine and Hypertension Division, AOU Città della Salute e della Scienza, Turin, Italy (E.B.); Fibromuscular Dysplasia Society of America, Rocky River, OH (P.M.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, F-75015 Paris, France (P.-F.P.); Université Paris-Descartes, Paris Sorbonne Cité, F-75006 Paris, France (P.-F.P.); and Université Paris-Descartes, Paris Sorbonne Cité; AP-HP, Department of Genetics, Hôpital Europeen Georges Pompidou; INSERM, UMR-S 970, PARCC, Paris, France (X.J.)
| | - Emmanuel Touzé
- From the Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique (A.P., E.B.), and Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. (A.P.); Department of Internal Medicine, Division of Nephrology and Hypertension, Universitair Ziekenhuis Brussel (Vrije Universiteit Brussel, VUB), Brussel, Belgium, (P.V.D.N.); Normandie Université, UNICAEN, Inserm U919, CHU Côte de Nacre, Caen, 14000 France (E.T.); Department of Cardiology, Ghent University Hospital, Ghent, Belgium (S.G.); Department of Medical Sciences, Internal Medicine and Hypertension Division, AOU Città della Salute e della Scienza, Turin, Italy (E.B.); Fibromuscular Dysplasia Society of America, Rocky River, OH (P.M.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, F-75015 Paris, France (P.-F.P.); Université Paris-Descartes, Paris Sorbonne Cité, F-75006 Paris, France (P.-F.P.); and Université Paris-Descartes, Paris Sorbonne Cité; AP-HP, Department of Genetics, Hôpital Europeen Georges Pompidou; INSERM, UMR-S 970, PARCC, Paris, France (X.J.)
| | - Sofie Gevaert
- From the Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique (A.P., E.B.), and Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. (A.P.); Department of Internal Medicine, Division of Nephrology and Hypertension, Universitair Ziekenhuis Brussel (Vrije Universiteit Brussel, VUB), Brussel, Belgium, (P.V.D.N.); Normandie Université, UNICAEN, Inserm U919, CHU Côte de Nacre, Caen, 14000 France (E.T.); Department of Cardiology, Ghent University Hospital, Ghent, Belgium (S.G.); Department of Medical Sciences, Internal Medicine and Hypertension Division, AOU Città della Salute e della Scienza, Turin, Italy (E.B.); Fibromuscular Dysplasia Society of America, Rocky River, OH (P.M.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, F-75015 Paris, France (P.-F.P.); Université Paris-Descartes, Paris Sorbonne Cité, F-75006 Paris, France (P.-F.P.); and Université Paris-Descartes, Paris Sorbonne Cité; AP-HP, Department of Genetics, Hôpital Europeen Georges Pompidou; INSERM, UMR-S 970, PARCC, Paris, France (X.J.)
| | - Elena Berra
- From the Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique (A.P., E.B.), and Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. (A.P.); Department of Internal Medicine, Division of Nephrology and Hypertension, Universitair Ziekenhuis Brussel (Vrije Universiteit Brussel, VUB), Brussel, Belgium, (P.V.D.N.); Normandie Université, UNICAEN, Inserm U919, CHU Côte de Nacre, Caen, 14000 France (E.T.); Department of Cardiology, Ghent University Hospital, Ghent, Belgium (S.G.); Department of Medical Sciences, Internal Medicine and Hypertension Division, AOU Città della Salute e della Scienza, Turin, Italy (E.B.); Fibromuscular Dysplasia Society of America, Rocky River, OH (P.M.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, F-75015 Paris, France (P.-F.P.); Université Paris-Descartes, Paris Sorbonne Cité, F-75006 Paris, France (P.-F.P.); and Université Paris-Descartes, Paris Sorbonne Cité; AP-HP, Department of Genetics, Hôpital Europeen Georges Pompidou; INSERM, UMR-S 970, PARCC, Paris, France (X.J.)
| | - Pamela Mace
- From the Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique (A.P., E.B.), and Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. (A.P.); Department of Internal Medicine, Division of Nephrology and Hypertension, Universitair Ziekenhuis Brussel (Vrije Universiteit Brussel, VUB), Brussel, Belgium, (P.V.D.N.); Normandie Université, UNICAEN, Inserm U919, CHU Côte de Nacre, Caen, 14000 France (E.T.); Department of Cardiology, Ghent University Hospital, Ghent, Belgium (S.G.); Department of Medical Sciences, Internal Medicine and Hypertension Division, AOU Città della Salute e della Scienza, Turin, Italy (E.B.); Fibromuscular Dysplasia Society of America, Rocky River, OH (P.M.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, F-75015 Paris, France (P.-F.P.); Université Paris-Descartes, Paris Sorbonne Cité, F-75006 Paris, France (P.-F.P.); and Université Paris-Descartes, Paris Sorbonne Cité; AP-HP, Department of Genetics, Hôpital Europeen Georges Pompidou; INSERM, UMR-S 970, PARCC, Paris, France (X.J.)
| | - Pierre-François Plouin
- From the Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique (A.P., E.B.), and Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. (A.P.); Department of Internal Medicine, Division of Nephrology and Hypertension, Universitair Ziekenhuis Brussel (Vrije Universiteit Brussel, VUB), Brussel, Belgium, (P.V.D.N.); Normandie Université, UNICAEN, Inserm U919, CHU Côte de Nacre, Caen, 14000 France (E.T.); Department of Cardiology, Ghent University Hospital, Ghent, Belgium (S.G.); Department of Medical Sciences, Internal Medicine and Hypertension Division, AOU Città della Salute e della Scienza, Turin, Italy (E.B.); Fibromuscular Dysplasia Society of America, Rocky River, OH (P.M.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, F-75015 Paris, France (P.-F.P.); Université Paris-Descartes, Paris Sorbonne Cité, F-75006 Paris, France (P.-F.P.); and Université Paris-Descartes, Paris Sorbonne Cité; AP-HP, Department of Genetics, Hôpital Europeen Georges Pompidou; INSERM, UMR-S 970, PARCC, Paris, France (X.J.)
| | - Xavier Jeunemaitre
- From the Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique (A.P., E.B.), and Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. (A.P.); Department of Internal Medicine, Division of Nephrology and Hypertension, Universitair Ziekenhuis Brussel (Vrije Universiteit Brussel, VUB), Brussel, Belgium, (P.V.D.N.); Normandie Université, UNICAEN, Inserm U919, CHU Côte de Nacre, Caen, 14000 France (E.T.); Department of Cardiology, Ghent University Hospital, Ghent, Belgium (S.G.); Department of Medical Sciences, Internal Medicine and Hypertension Division, AOU Città della Salute e della Scienza, Turin, Italy (E.B.); Fibromuscular Dysplasia Society of America, Rocky River, OH (P.M.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, F-75015 Paris, France (P.-F.P.); Université Paris-Descartes, Paris Sorbonne Cité, F-75006 Paris, France (P.-F.P.); and Université Paris-Descartes, Paris Sorbonne Cité; AP-HP, Department of Genetics, Hôpital Europeen Georges Pompidou; INSERM, UMR-S 970, PARCC, Paris, France (X.J.)
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Exome sequencing in seven families and gene-based association studies indicate genetic heterogeneity and suggest possible candidates for fibromuscular dysplasia. J Hypertens 2016; 33:1802-10; discussion 1810. [PMID: 26147384 DOI: 10.1097/hjh.0000000000000625] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, aneurysm and dissection, mainly of renal arteries and carotids. FMD occurs predominantly in women with nearly four out of 1000 prevalence and cause hypertension, renal ischemia or stroke. The pathogenesis of FMD is unknown and a genetic origin is suspected given its demonstrated familial aggregation. METHOD We performed whole exome sequencing (WES) in 16 cases (seven families). Coding variants in 3971 genes were prioritized on frequency (minor allele frequency < 0.01) and in silico predicted functionality. RESULTS No gene harbours variants that are shared among all affected members of at least three families. Variants from 16 genes of vascular and connective tissue diseases are excluded as causative in these families. Genes with at least four variants in the 16 patients and vascular genes were followed-up using genotypes from 249 unrelated cases and 689 controls. Gene-based association analyses using SKAT-O shows nominal significant association with multifocal FMD (N = 164) for myosin light chain kinase (MYLK, P = 0.01) previously involved in thoracic aortic aneurysm, obscurin (OBSCN), a sarcomeric protein (P = 0.003), dynein cytoplasmic heavy chain 1 (DYNC2H1, P = 0.02) and RNF213 previously associated with Moyamoya disease (P = 0.01). CONCLUSION Our study indicates genetic heterogeneity and the unlikely existence of a major gene for FMD and excludes the role of several vascular genes in familial FMD. We also suggest four possible candidate genes for multifocal FMD, though these findings need further genetic and functional confirmation. More powerful WES and association studies [e.g. genome-wide association study (GWAS)] will better decipher the genetic basis of FMD.
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23
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Shivapour DM, Erwin P, Kim ES. Epidemiology of fibromuscular dysplasia: A review of the literature. Vasc Med 2016; 21:376-81. [PMID: 27067138 DOI: 10.1177/1358863x16637913] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory disease of medium sized arteries that has been described in multiple anatomic territories with a wide variety of manifestations (e.g. beading, stenosis, occlusion, aneurysm, or dissection). While the first case of FMD is thought to have been described over 75 years ago, the causes, natural history, and epidemiology of FMD in the general population remain incompletely understood. This article reviews important historical and contemporary contributions to the FMD literature that inform our current understanding of the prevalence and epidemiology of this important disorder. A particular focus is given to studies which form the basis for FMD prevalence estimates. Prevalence estimates for renal FMD are derived from renal transplant donor studies and sub-studies of clinical trials of renal artery stenting; however, it is unclear how well these estimates generalize to the overall population as a whole. Newer data are emerging examining the genetic associations and environmental interactions with FMD. Significant contributions to the understanding of FMD have come from the United States Registry for Fibromuscular Dysplasia; however, many unanswered questions remain, and future studies are required to further characterize FMD epidemiology in general populations and advance our understanding of this important disorder.
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Affiliation(s)
| | - Phillip Erwin
- Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Esther Sh Kim
- Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA
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24
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Sanidas EA, Seferou M, Papadopoulos DP, Makris A, Viniou NA, Chantziara V, Cennimata V, Papademetriou V. Renal Fibromuscular Dysplasia: A Not So Common Entity of Secondary Hypertension. J Clin Hypertens (Greenwich) 2016; 18:240-6. [PMID: 26970300 PMCID: PMC8031778 DOI: 10.1111/jch.12650] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2015] [Revised: 07/01/2015] [Accepted: 07/05/2015] [Indexed: 11/28/2022]
Abstract
Fibromuscular dysplasia is a rare noninflammatory vascular disease characterized by nonatheroslerotic stenosis predominantly seen in young women, whereas the majority of cases involve the renal arteries causing secondary hypertension. Most noninvasive screening tests are not quite sensitive or reproducible to rule out renal artery stenosis, but renal angiography usually confirms the diagnosis. Percutaneous renal artery angioplasty is the treatment of choice; however, it may not result in normalization of blood pressure if diagnosis is delayed. Continued follow-up is necessary since stenosis reoccurs.
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Affiliation(s)
- Elias A. Sanidas
- ESH Center of Excellence for Hypertension“Laiko” General HospitalAthensGreece
| | - Maria Seferou
- ESH Center of Excellence for Hypertension“Laiko” General HospitalAthensGreece
| | | | - Anastasios Makris
- ESH Center of Excellence for Hypertension“Laiko” General HospitalAthensGreece
| | - Nora A. Viniou
- ESH Center of Excellence for Hypertension“Laiko” General HospitalAthensGreece
| | - Vasiliki Chantziara
- ESH Center of Excellence for Hypertension“Laiko” General HospitalAthensGreece
| | - Vasiliki Cennimata
- ESH Center of Excellence for Hypertension“Laiko” General HospitalAthensGreece
| | - Vasilios Papademetriou
- Hypertension and Cardiovascular Research ClinicVeterans Affairs and Georgetown University Medical CentersWashingtonDCUSA
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Affiliation(s)
- Sarah C O'Connor
- Cleveland Clinic Lerner College of Medicine, Case Western University, Cleveland, OH
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27
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Makino Y, Inokuchi G, Yokota H, Hayakawa M, Yajima D, Motomura A, Chiba F, Torimitsu S, Nakatani Y, Iwase H. Sudden death due to coronary artery dissection associated with fibromuscular dysplasia revealed by postmortem selective computed tomography coronary angiography: A case report. Forensic Sci Int 2015; 253:e10-5. [PMID: 26048864 DOI: 10.1016/j.forsciint.2015.05.015] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Revised: 05/13/2015] [Accepted: 05/14/2015] [Indexed: 11/29/2022]
Abstract
We present an autopsy case of sudden death due to coronary artery dissection associated with fibromuscular dysplasia (FMD) in a young female patient. Postmortem selective coronary artery computed tomography (CT) angiography revealed dissections of the left anterior descending and left circumflex arteries. These findings were confirmed by subsequent autopsy. Histopathological examination revealed coronary artery FMD, which is considered a risk factor for dissection. To the best of our knowledge, this is the first postmortem radiology-pathology correlation of coronary artery dissection associated with FMD.
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Affiliation(s)
- Yohsuke Makino
- Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 113-0033, Tokyo, Japan; Department of Legal Medicine, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku 260-8670, Chiba, Japan.
| | - Go Inokuchi
- Department of Legal Medicine, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku 260-8670, Chiba, Japan.
| | - Hajime Yokota
- Department of Radiology, Chiba University Hospital, Inohana 1-8-1, Chuo-ku 260-8677, Chiba, Japan.
| | - Mutsumi Hayakawa
- Department of Legal Medicine, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku 260-8670, Chiba, Japan.
| | - Daisuke Yajima
- Department of Legal Medicine, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku 260-8670, Chiba, Japan.
| | - Ayumi Motomura
- Department of Legal Medicine, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku 260-8670, Chiba, Japan.
| | - Fumiko Chiba
- Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 113-0033, Tokyo, Japan; Department of Legal Medicine, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku 260-8670, Chiba, Japan.
| | - Suguru Torimitsu
- Department of Legal Medicine, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku 260-8670, Chiba, Japan.
| | - Yukio Nakatani
- Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku 260-8670, Chiba, Japan.
| | - Hirotaro Iwase
- Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 113-0033, Tokyo, Japan; Department of Legal Medicine, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku 260-8670, Chiba, Japan.
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Abstract
The main objectives of this expert consensus are to raise awareness about fibromuscular dysplasia, which is more frequent and more often systemic than previously thought and can sometimes have devastating consequences; to provide up-to-date recommendations for the diagnosis, evaluation, and management of the disease; and to identify research priorities. The emphasis has been put on recommendations for daily practice. The main topics covered include definition, classification, diagnosis, and management of fibromuscular dysplasia in adult patients with symptomatic involvement of the renal arteries, supra-aortic trunks, and digestive and peripheral arteries.
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29
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Silhol F, Sarlon-Bartoli G, Daniel L, Bartoli JM, Cohen S, Lepidi H, Piquet P, Bartoli MA, Vaïsse B. Intranuclear Expression of Progesterone Receptors in Smooth Muscle Cells of Renovascular Fibromuscular Dysplasia: A Pilot Study. Ann Vasc Surg 2015; 29:830-5. [DOI: 10.1016/j.avsg.2014.10.025] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Revised: 10/26/2014] [Accepted: 10/27/2014] [Indexed: 11/16/2022]
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Varennes L, Tahon F, Kastler A, Grand S, Thony F, Baguet JP, Detante O, Touzé E, Krainik A. Fibromuscular dysplasia: what the radiologist should know: a pictorial review. Insights Imaging 2015; 6:295-307. [PMID: 25926266 PMCID: PMC4444794 DOI: 10.1007/s13244-015-0382-4] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Revised: 12/23/2014] [Accepted: 01/13/2015] [Indexed: 11/06/2022] Open
Abstract
Abstract Fibromuscular dysplasia (FMD) is an idiopathic, segmentary, non-inflammatory and non-atherosclerotic disease that can affect all layers of both small- and medium-calibre arteries. The prevalence of FMD is estimated between 4 and 6 % in the renal arteries and between 0.3 and 3 % in the cervico-encephalic arteries. FMD most frequently affects the renal, carotid and vertebral arteries, but it can theoretically affect any artery. Radiologists play an important role in the diagnosis of FMD, and good knowledge of FMD’s signs will certainly help reduce the delay between the first symptoms and diagnosis. The common string-of-beads aspect is well known, but less common presentations also have to be considered. These less common imaging findings include vascular loops, fusiform vascular ectasia, arterial dissection, aneurysm and subarachnoid haemorrhage. These radiologic presentations should be known by radiologists in order to diagnose possible FMD, particularly when present in young females or when associated with personal or familial hypertension, to reduce the delay between the onset of the first symptom and the final diagnosis. The patients have to be referred to specialised FMD centres for dedicated management. Teaching Points • Fibromuscular dysplasia is not a rare disease. • Radiologists should recognise less common presentations to orient specific management. • Vascular loops, fusiform vascular ectasia and a “string-of-beads” aspect are typical presentations. • Arterial dissection, aneurysm and subarachnoid haemorrhage are less typical radiologic presentations.
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Affiliation(s)
- L Varennes
- Department of Neuroradiology and MRI, University Hospital of Grenoble, CS 10217-38043, Grenoble Cedex 09, France
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Pagliaro B, Tocci G, Pagannone E, Musumeci MB, Testa M, Sensini I, Autore C, Ferrucci A, Volpe M. An atypical clinical presentation of renovascular hypertension. Int J Cardiol 2014; 177:e107-10. [PMID: 25300660 DOI: 10.1016/j.ijcard.2014.09.085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2014] [Accepted: 09/20/2014] [Indexed: 11/19/2022]
Affiliation(s)
- Beniamino Pagliaro
- Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome "Sapienza", Sant'Andrea Hospital, Rome, Italy
| | - Giuliano Tocci
- Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome "Sapienza", Sant'Andrea Hospital, Rome, Italy; IRCCS Neuromed, Pozzilli, IS, Italy
| | - Erika Pagannone
- Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome "Sapienza", Sant'Andrea Hospital, Rome, Italy
| | - M Beatrice Musumeci
- Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome "Sapienza", Sant'Andrea Hospital, Rome, Italy
| | - Marco Testa
- Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome "Sapienza", Sant'Andrea Hospital, Rome, Italy
| | - Isabella Sensini
- Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome "Sapienza", Sant'Andrea Hospital, Rome, Italy
| | - Camillo Autore
- Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome "Sapienza", Sant'Andrea Hospital, Rome, Italy
| | - Andrea Ferrucci
- Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome "Sapienza", Sant'Andrea Hospital, Rome, Italy
| | - Massimo Volpe
- Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome "Sapienza", Sant'Andrea Hospital, Rome, Italy; IRCCS Neuromed, Pozzilli, IS, Italy.
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Sharma AM, Norton PT, Zhu D. Conditions presenting with symptoms of peripheral arterial disease. Semin Intervent Radiol 2014; 31:281-91. [PMID: 25435652 DOI: 10.1055/s-0034-1393963] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Peripheral artery disease (PAD) is estimated to affect more than 20% of people older than 65 years. The vast majority of patients with symptoms suggestive of PAD have atherosclerosis often associated with conventional vascular risk factors such as smoking, diabetes, dyslipidemia, and inflammation. A minority of people presenting with symptoms suggesting PAD have an alternative etiology. These groups of disorders are often underdiagnosed, and if diagnosed correctly the diagnosis may be delayed. Understanding these pathologies well is important, as they can be very debilitating and optimal treatment may vary significantly. Inappropriate treatment of these disorders can lead to worsening morbidity and mortality. This article discusses the underlying causes of nonatherosclerotic PAD, including the diagnosis and treatment of these disorders.
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Affiliation(s)
- Aditya M Sharma
- Division of Cardiovascular Medicine, University of Virginia, Charlottesville, Virginia
| | - Patrick T Norton
- Department of Radiology, University of Virginia, Charlottesville, Virginia
| | - Daisy Zhu
- Medical Education, University Virginia School of Medicine, University of Virginia, Charlottesville, Virginia
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Michelis KC, Olin JW, Kadian-Dodov D, d'Escamard V, Kovacic JC. Coronary artery manifestations of fibromuscular dysplasia. J Am Coll Cardiol 2014; 64:1033-46. [PMID: 25190240 DOI: 10.1016/j.jacc.2014.07.014] [Citation(s) in RCA: 100] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Revised: 07/10/2014] [Accepted: 07/11/2014] [Indexed: 01/25/2023]
Abstract
Fibromuscular dysplasia (FMD) involving the coronary arteries is an uncommon but important condition that can present as acute coronary syndrome, left ventricular dysfunction, or potentially sudden cardiac death. Although the classic angiographic "string of beads" that may be observed in renal artery FMD does not occur in coronary arteries, potential manifestations include spontaneous coronary artery dissection, distal tapering or long, smooth narrowing that may represent dissection, intramural hematoma, spasm, or tortuosity. Importantly, FMD must be identified in at least one other noncoronary arterial territory to attribute any coronary findings to FMD. Although there is limited evidence to guide treatment, many lesions heal spontaneously; thus, a conservative approach is generally preferred. The etiology is poorly understood, but there are ongoing efforts to better characterize FMD and define its genetic and molecular basis. This report reviews the clinical course of FMD involving the coronary arteries and provides guidance for diagnosis and treatment strategies.
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Affiliation(s)
- Katherine C Michelis
- Zena and Michael A. Wiener Cardiovascular Institute, and Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jeffrey W Olin
- Zena and Michael A. Wiener Cardiovascular Institute, and Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York.
| | - Daniella Kadian-Dodov
- Zena and Michael A. Wiener Cardiovascular Institute, and Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Valentina d'Escamard
- Zena and Michael A. Wiener Cardiovascular Institute, and Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jason C Kovacic
- Zena and Michael A. Wiener Cardiovascular Institute, and Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York.
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Escárcega RO, Mathur M, Franco JJ, Alkhouli M, Patel C, Singh K, Bashir R, Patil P. Nonatherosclerotic obstructive vascular diseases of the mesenteric and renal arteries. Clin Cardiol 2014; 37:700-6. [PMID: 25099891 DOI: 10.1002/clc.22305] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2014] [Accepted: 05/27/2014] [Indexed: 12/31/2022] Open
Abstract
Nonatherosclerotic vascular diseases of the mesenteric and renal arteries are considered to occur less frequently than those caused by occlusive atherosclerotic disease. However, when present, they pose a significant diagnostic and therapeutic challenge. Such disorders include fibromuscular dysplasia, median arcuate ligament syndrome, the renal nutcracker syndrome, and some forms of acute and chronic mesenteric ischemia (embolic and thrombotic). This is a heterogeneous group of disorders with substantial differences in the pathogenesis and diagnostic approaches to these diseases. We provide an overview of the pathogenesis, clinical presentation, diagnosis, and current management of fibromuscular dysplasia, median arcuate ligament syndrome, and the renal nutcracker syndrome.
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Affiliation(s)
- Ricardo O Escárcega
- Department of Cardiology, MedStar Washington Hospital Center, Washington, DC
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Chrysant SG, Chrysant GS. Treatment of hypertension in patients with renal artery stenosis due to fibromuscular dysplasia of the renal arteries. Cardiovasc Diagn Ther 2014; 4:36-43. [PMID: 24649423 DOI: 10.3978/j.issn.2223-3652.2014.02.01] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2013] [Accepted: 01/27/2014] [Indexed: 11/14/2022]
Abstract
Renal artery stenosis (RAS) from fibromuscular dysplasia (FMD) is an uncommon cause of hypertension that affects mostly women. FMD is a noninflammatory vascular disease that predominantly affects mainly the renal arteries, but can also affect arteries in other vascular territories. The most common type of FMD is the media fibroplasia with the characteristic "string of beads" appearance (80-90%), whereas the two other types, the "intimal" and "adventitial" FMD are much less common accounting for 10% and <5% of cases, respectively. The prevalence of FMD in the general population is not well known. Estimates are derived from screening kidney donors, with a prevalence of about 2.6%. Among patients with renovascular hypertension (RVH), its incidence is about 10%, whereas 80-90% of RVH is due to atherosclerotic renal artery stenosis (ARAS). The treatment of choice of hypertension due to FMD is percutaneous renal angioplasty (PTRA). In contrast, hypertension due to ARAS is not frequently responsive to PTRA. In order to achieve successful control of hypertension in patients with FMD, a combination of PTRA with drugs that block the renin-angiotensin-aldosterone system (RAAS) is often necessary. The purpose of this review was to search the literature for newer diagnostic methods and treatment of FMD. Therefore, a Medline search of the English literature of published papers between 2008 and December 2013 was performed. Of 58 papers reviewed, 19 pertinent papers were selected including, studies, reviews, registries and case reports. The information from these studies together with collateral literature will be discussed in this concise review.
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Affiliation(s)
- Steven G Chrysant
- 1 University of Oklahoma College of Medicine, 2 INTEGRIS Baptist Medical Center, Oklahoma City, OK, USA
| | - George S Chrysant
- 1 University of Oklahoma College of Medicine, 2 INTEGRIS Baptist Medical Center, Oklahoma City, OK, USA
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Olin JW, Gornik HL, Bacharach JM, Biller J, Fine LJ, Gray BH, Gray WA, Gupta R, Hamburg NM, Katzen BT, Lookstein RA, Lumsden AB, Newburger JW, Rundek T, Sperati CJ, Stanley JC. Fibromuscular dysplasia: state of the science and critical unanswered questions: a scientific statement from the American Heart Association. Circulation 2014; 129:1048-78. [PMID: 24548843 DOI: 10.1161/01.cir.0000442577.96802.8c] [Citation(s) in RCA: 292] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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An X, Jiang X, Dong H, Peng M, Zou Y, Song L, Guan T, Zhou X, Yang Y. Fibromuscular dysplasia affecting a two-branched renal artery in a patient with a solitary kidney: case presentation. Clin Cardiol 2013; 36:E7-10. [PMID: 23780717 DOI: 10.1002/clc.22149] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Revised: 04/26/2013] [Indexed: 01/09/2023] Open
Abstract
Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory arterial disease, commonly involving the renal arteries. Here we report a case of a 16-year-old Chinese male who was found to have severe hypertension with proteinuria for 2 years. Computed tomography showed absence of the left kidney and enlargement of the right kidney. Subsequent angiography confirmed the above findings and revealed narrowing of both the upper and lower branches of the right renal artery caused by FMD. These combined lesions are very rare, and individuals affected are at increased risk of renal dysfunction if left untreated. Treatment with percutaneous balloon angioplasty is the first choice in such a patient and usually results in optimal outcomes.
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Affiliation(s)
- Xuanqi An
- Hypertension Center, Department of Cardiology, Fuwai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Savard S, Azarine A, Jeunemaitre X, Azizi M, Plouin PF, Steichen O. Association of Smoking With Phenotype at Diagnosis and Vascular Interventions in Patients With Renal Artery Fibromuscular Dysplasia. Hypertension 2013; 61:1227-32. [DOI: 10.1161/hypertensionaha.111.00838] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Affiliation(s)
- Sébastien Savard
- From the Hypertension Unit (S.S., M.A., P.-F.P.), Department of Vascular Radiology (A.A.), Department of Genetics and Reference Centre for Rare Vascular Diseases (X.J.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Université Paris-Descartes, Faculté de Médecine, Paris, France (X.J., M.A., P.-F.P.); INSERM, UMRS 970, Paris Cardiovascular Research Center, Paris, France (X.J.); Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Department of Internal
| | - Arshid Azarine
- From the Hypertension Unit (S.S., M.A., P.-F.P.), Department of Vascular Radiology (A.A.), Department of Genetics and Reference Centre for Rare Vascular Diseases (X.J.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Université Paris-Descartes, Faculté de Médecine, Paris, France (X.J., M.A., P.-F.P.); INSERM, UMRS 970, Paris Cardiovascular Research Center, Paris, France (X.J.); Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Department of Internal
| | - Xavier Jeunemaitre
- From the Hypertension Unit (S.S., M.A., P.-F.P.), Department of Vascular Radiology (A.A.), Department of Genetics and Reference Centre for Rare Vascular Diseases (X.J.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Université Paris-Descartes, Faculté de Médecine, Paris, France (X.J., M.A., P.-F.P.); INSERM, UMRS 970, Paris Cardiovascular Research Center, Paris, France (X.J.); Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Department of Internal
| | - Michel Azizi
- From the Hypertension Unit (S.S., M.A., P.-F.P.), Department of Vascular Radiology (A.A.), Department of Genetics and Reference Centre for Rare Vascular Diseases (X.J.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Université Paris-Descartes, Faculté de Médecine, Paris, France (X.J., M.A., P.-F.P.); INSERM, UMRS 970, Paris Cardiovascular Research Center, Paris, France (X.J.); Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Department of Internal
| | - Pierre-François Plouin
- From the Hypertension Unit (S.S., M.A., P.-F.P.), Department of Vascular Radiology (A.A.), Department of Genetics and Reference Centre for Rare Vascular Diseases (X.J.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Université Paris-Descartes, Faculté de Médecine, Paris, France (X.J., M.A., P.-F.P.); INSERM, UMRS 970, Paris Cardiovascular Research Center, Paris, France (X.J.); Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Department of Internal
| | - Olivier Steichen
- From the Hypertension Unit (S.S., M.A., P.-F.P.), Department of Vascular Radiology (A.A.), Department of Genetics and Reference Centre for Rare Vascular Diseases (X.J.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Université Paris-Descartes, Faculté de Médecine, Paris, France (X.J., M.A., P.-F.P.); INSERM, UMRS 970, Paris Cardiovascular Research Center, Paris, France (X.J.); Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Department of Internal
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41
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Shared associations of nonatherosclerotic, large-vessel, cerebrovascular arteriopathies. Curr Opin Neurol 2013; 26:13-28. [DOI: 10.1097/wco.0b013e32835c607f] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Savard S, Steichen O, Azarine A, Azizi M, Jeunemaitre X, Plouin PF. Association between 2 angiographic subtypes of renal artery fibromuscular dysplasia and clinical characteristics. Circulation 2012; 126:3062-9. [PMID: 23155180 DOI: 10.1161/circulationaha.112.117499] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Initially based on histology, the diagnosis of renal artery fibromuscular dysplasia (FMD) is now based mostly on angiographic appearance because arterial tissue samples are rarely available. This retrospective cross-sectional study aimed to assess the clinical relevance of a binary angiographic classification of FMD lesions (unifocal or multifocal) based on computed tomographic or magnetic resonance angiography. METHODS AND RESULTS Adult patients diagnosed with FMD in a single tertiary care center for hypertension management were identified by screening of electronic files. FMD lesions were reviewed and classified according to computed tomography or magnetic resonance angiography as multifocal if there were at least 2 stenoses in the same arterial segment; otherwise, they were classified as unifocal. Of 337 patients with established renal artery FMD, 276 (82%) were classified as multifocal. Patients with unifocal and multifocal lesions differed significantly in median age at diagnosis of FMD (30 and 49 years) and hypertension (26 and 40 years), sex distribution (female:male ratio, 2:1 and 5:1), initial blood pressure (157/97 and 146/88 mm Hg), current smoking (50% and 26%), prevalence of unilateral renal artery lesions (79% and 38%), presence of kidney asymmetry (33% and 10%), renal revascularization procedures (90% and 35%), and hypertension cure rates in patients who underwent revascularization (54% and 26%). CONCLUSIONS A binary angiographic classification into unifocal or multifocal renal artery FMD is straightforward and discriminates 2 groups of patients with different clinical phenotypes.
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Affiliation(s)
- Sébastien Savard
- Assistance Publique-Hoˆpitaux de Paris, Hoˆpital Europe´en Georges-Pompidou, Hypertension Unit, Paris, F-75015, France
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Poloskey SL, Kim ES, Sanghani R, Al-Quthami AH, Arscott P, Moran R, Rigelsky CM, Gornik HL. Low yield of genetic testing for known vascular connective tissue disorders in patients with fibromuscular dysplasia. Vasc Med 2012; 17:371-8. [PMID: 23064905 DOI: 10.1177/1358863x12459650] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Patients with fibromuscular dysplasia (FMD) may have clinical features consistent with Mendelian vascular connective tissue disorders. The yield of genetic testing for these disorders among patients with FMD has not been determined. A total of 216 consecutive patients with FMD were identified. Clinical characteristics were collected and genetic test results reviewed for abnormalities in the following genes: transforming growth factor-β receptor 1 and 2 (TGFβR1 and TGFβR2), collagen 3A1, fibrillin-1, smooth muscle α-actin 2, and SMAD3. A total of 63 patients (63/216; 29.2%) were referred for genetic counseling with testing performed in 35 (35/63; 55.6%). The percentage of patients with a history of arterial or aortic dissection, history of aortic aneurysm, systemic features of a connective tissue disorder, and a family history of sudden death was significantly larger in the group that underwent genetic testing (62.9% vs 18.2%, p < 0.001; 8.6% vs 1.7%, p = 0.02; 51.4% vs 17.1%, p < 0.001; and 42.9% vs 22.7%, p = 0.04, respectively). Two patients were found to have distinct variants in the TGFβR1 gene (c.611 C>T, p.Thr204lle and c.1285 T>C, p.Tyr429His). The yield of genetic testing for vascular connective tissue disorders was low in a high-risk subset of FMD patients. However, two patients with a similar phenotype had novel and distinct variants in the TGFβR1 gene, a finding which merits further investigation.
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Affiliation(s)
- Stacey L Poloskey
- Cleveland Clinic Heart and Vascular Institute and the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
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Olin JW, Froehlich J, Gu X, Bacharach JM, Eagle K, Gray BH, Jaff MR, Kim ESH, Mace P, Matsumoto AH, McBane RD, Kline-Rogers E, White CJ, Gornik HL. The United States Registry for Fibromuscular Dysplasia: results in the first 447 patients. Circulation 2012; 125:3182-90. [PMID: 22615343 DOI: 10.1161/circulationaha.112.091223] [Citation(s) in RCA: 358] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Fibromuscular dysplasia (FMD), a noninflammatory disease of medium-size arteries, may lead to stenosis, occlusion, dissection, and/or aneurysm. There has been little progress in understanding the epidemiology, pathogenesis, and outcomes since its first description in 1938. METHODS AND RESULTS Clinical features, presenting symptoms, and vascular events are reviewed for the first 447 patients enrolled in a national FMD registry from 9 US sites. Vascular beds were imaged selectively based on clinical presentation and local practice. The majority of patients were female (91%) with a mean age at diagnosis of 51.9 (SD 13.4 years; range, 5-83 years). Hypertension, headache, and pulsatile tinnitus were the most common presenting symptoms of the disease. Self-reported family history of stroke (53.5%), aneurysm (23.5%), and sudden death (19.8%) were common, but FMD in first- or second-degree relatives was reported only in 7.3%. FMD was identified in the renal artery in 294 patients, extracranial carotid arteries in 251 patients, and vertebral arteries in 82 patients. A past or presenting history of vascular events were common: 19.2% of patients had a transient ischemic attack or stroke, 19.7% had experienced arterial dissection(s), and 17% of patients had an aneurysm(s). The most frequent indications for therapy were hypertension, aneurysm, and dissection. CONCLUSIONS In this registry, FMD occurred primarily in middle-aged women, although it presents across the lifespan. Cerebrovascular FMD occurred as frequently as renal FMD. Although a significant proportion of FMD patients may present with a serious vascular event, many present with nonspecific symptoms and a subsequent delay in diagnosis.
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Affiliation(s)
- Jeffrey W Olin
- Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1033, New York, NY 10029, USA.
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Persu A, Touzé E, Mousseaux E, Barral X, Joffre F, Plouin PF. Diagnosis and management of fibromuscular dysplasia: an expert consensus. Eur J Clin Invest 2012; 42:338-47. [PMID: 21854373 DOI: 10.1111/j.1365-2362.2011.02577.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Alexandre Persu
- Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
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Slemp SN, Hoover RL, Prahlow JA. Sudden Death in 14 Month Old Due to Fibromuscular Dysplasia of Atrioventricular Nodal Artery. Acad Forensic Pathol 2011. [DOI: 10.23907/2011.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory vascular disease that is most commonly found in the renal arteries of pre-menopausal women. However, this disease entity has rarely been described in the coronary arteries and small cardiac conduction arteries. To our knowledge, there is no recorded case of fibromuscular dysplasia in small cardiac conduction arteries in infants/children. In this report, we present a case of unexplained death of a 14 month old wherein routine histologic examination failed to reveal a cause of death, but subsequent submission of the cardiac conduction system (atrioventricular [AV] and sinoatrial [SA] node regions) demonstrated the presence of isolated AV nodal artery fibromuscular dysplasia, which was considered the cause of death. The case serves to emphasize the potential importance of evaluating the cardiac conduction system in cases where routine gross and microscopic autopsy fails to reveal an adequate explanation for death.
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Affiliation(s)
- Stephanie N. Slemp
- Indiana University School of Medicine-South Bend at the University of Notre Dame, South Bend, IN
| | - Rick L. Hoover
- Indiana University School of Medicine-South Bend at the University of Notre Dame, South Bend, IN
| | - Joseph A. Prahlow
- South Bend Medical Foundation in South Bend, IN, where he performs forensic and hospital autopsies, and a professor of pathology at Indiana University School of Medicine-South Bend at the University of Notre Dame
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Renal FMD may not confer a familial hypertensive risk nor is it caused by ACTA2 mutations. Pediatr Nephrol 2011; 26:1857-61. [PMID: 21553326 DOI: 10.1007/s00467-011-1891-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2010] [Revised: 04/04/2011] [Accepted: 04/04/2011] [Indexed: 10/18/2022]
Abstract
Renal fibromuscular dysplasia (FMD) can cause hypertension, and previous reports suggest that FMD is familial. We hypothesized that, in families containing an individual with proven FMD, relatives of index cases would have an increased risk of hypertension. ACTA2 mutations cause a spectrum of extra-renal arteriopathy, leading to our second hypothesis that mutations are implicated in FMD. The blood pressure of first-degree relatives was measured using standard devices and, when indicated, with 24-h ambulatory monitoring. Leucocyte DNA was obtained from FMD index cases and ACTA2 sequenced. Thirteen unrelated index cases, aged 2-32 (median 15) years, were recruited. Blood pressure was assessed in 40 first-degree relatives, comprising 22 parents aged 28-58 (median 44) years and 18 siblings aged 3-30 (median 13) years. Hypertension was evident in six (27%) parents but in none of the eight adult siblings. Of the ten screened siblings aged less than 18 years, one teenager was pre-hypertensive (90th-95th centile), the remainder being normotensive. No ACTA2 mutations were found in 13 index cases. Hypertension was evident in 20% of all assessed adult first-degree relatives and is therefore not increased relative to 25% of the adult population. Although hypertensive parents did not undergo angiography to assign FMD status, this observation, together with the lack of hypertension in 18 siblings, indicates that FMD is unlikely to confer an excess hypertension risk in first-degree relatives up to middle-age. Furthermore, in our cohort, FMD was not caused by ACTA2 mutations.
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Okazaki J, Guntani A, Homma K, Kyuragi R, Kawakubo E, Maehara Y. Fibromuscular dysplasia of the lower extremities. Ann Vasc Dis 2011; 4:143-9. [PMID: 23555446 DOI: 10.3400/avd.cr.10.01027] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2010] [Accepted: 03/09/2011] [Indexed: 11/13/2022] Open
Abstract
Fibromuscular dysplasia (FMD) is a nonatherosclerotic, non-inflammatory vascular disease that mainly affects the renal and internal carotid arteries. Involvement of other sites, including arteries of the extremities, is uncommon, and only a few histologically confirmed cases have been reported. FMD of the arteries of the extremities can result in ischemia requiring surgical or endovascular reconstruction. In the present report, two cases of FMD are described: one case of femoropopliteal artery occlusive disease, and one case of nonsymptomatic progression of external iliac artery dissection, both with histological confirmation of FMD. Clinical presentation, treatment, outcome and histological findings of previously reported cases are reviewed. FMD should be considered as a cause of occlusion, stenosis, dissection or aneurysm of the peripheral arteries: although rare, it can lead to limb-threatening ischemia or life-threatening aneurysm rupture.
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Affiliation(s)
- Jin Okazaki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan
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Abstract
Fibromuscular dysplasia (FMD) encompasses a heterogeneous group of idiopathic, segmental, nonatherosclerotic diseases of the musculature of arterial walls, leading to the narrowing of small and medium-sized arteries. The most common locations of FMD are renal arteries and carotid arteries. The diagnosis of FMD is made on the "string of beads" appearance of the arteries. The French Health Authority recommends performing a CT scan or an MRA to assess the diagnosis of FMD. A recent meta-analysis showed the cure rates using current definitions of hypertension cure are only 36% and 54% after angioplasty and surgery, respectively.
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Abstract
This is the first report that presents renal transplantation after bilateral nephrectomy as the final treatment for severe renovascular hypertension due to fibromuscular dysplasia (FMD). We describe the history of a 1-year-old girl who suffered from renovascular hypertension due to FMD. Imaging revealed multiple bilateral stenoses of the renal artery extending into the distal branches. The hypertension proved unresponsive to pharmacologic treatment and the intrarenal peripherally located stenoses rendered a conventional approach such as transluminal or surgical angioplasty not feasible. At the age of 5 years, a unilateral nephrectomy of the most affected kidney was performed, but she remained hypertensive and developed progressive cardiomyopathy and retinopathy. At the age of 6 years the remaining kidney was removed, followed by a living related renal transplantation with a kidney donated by her mother. Posttransplantation, she developed mild hypertension due to a postanastomotic stenosis, which was easily controlled with antihypertensives. Now 8 years after transplantation, she has experienced no further blood pressure related problems. Although there is a risk of recurrence of FMD after performing a living related transplantation, our report suggests that this procedure is relatively safe, provided appropriate preoperative evaluation and follow up is performed.
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Affiliation(s)
- N B B Knops
- Department of Pediatric Nephrology and Solid Organ Transplantation, University Hospitals Leuven, Belgium.
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