Discontinuous polyostotic fibrous dysplasia with multiple systemic disorders and unique genetic mutations: A case report

Table 1 Laboratory tests

Parameter	Unit	Reference	Result
Parathyroid hormone	pg/mL	15.3-68.3	23.7
25-OH-VitD	nmol/L	47.7-144	121.40
Osteocalcin	ng/mL	Male, 9.80-26.40; Female, 7.70-21.70	7.05
Calcium	mmol/L	2.08-2.80	2.61
Serum phosphate	mmol/L	1.00-1.94	1.61
Cortisol, 8:00-10:00	nmol/L	147.3-609.3	1492.00
Triglyceride	mmol/L	< 1.70	1.88
Uric acid	μmol/L	150-360	689
Bone specific alkaline phosphatase	μg/L	11.4-24.0	15.86
Hematocrit	%	Male, 41-53; Female, 36-46	47.80
Eosinophils	%	1-3	8.10

25-OH-VitD: 25-Hydroxy vitamin D.

Table 2 Cases diagnosed as polyostotic fibrous dysplasia

Ref.	Year	Sex	Age	Location	Appendix	Treatment	Outcome
Sagmeister et al[12]	2016	F	27	Throughout the skeleton. Transverse fracture of the distal right femur	Continuous lesions, extensive bone expansion, cyst formation, cortical loss	Skin traction for 8 wk. Intensive physiotherapy for the fracture	Recovered well, returning to baseline 3 mo later
Wu et al[2]	2014	F	38	Sternum, thoracic spine, ribs, right femur, and tibia	Multiple lytic, expansile lesions, continuous pathologic fractures in the thoracic spine	Surgical therapy. Diphosphate therapy with Vit D and calcium	Completely recovered. Able to participate in daily life and work 2 yr later
Kodama et al[10]	2012	F	8	Right pelvis, bilateral femurs, and fibula	Discontinuous lesions	Thigh coxa valga osteotomy and plate fixation. Diphosphate therapy	No complaints of severe pain in lower extremity. Low bone turn-over rate
Aras et al[9]	2012	M	48	Cranium, left hemithorax, bilateral upper, lower extremities, and pelvic bones	Continuous lesions, bladder cancer	No treatment reported	No outcome reported
Boston et al[8]	1994	M	3.3	Proximal left femur and proximal left humerus	Albright-McCune syndrome, no café-au-lait pigmentation, Cushing syndrome	Bilateral adrenalectomy at 7-yr-old with steroid replacement	Cushing syndrome removed. Still with prepubertal and elevated liver enzyme
Lourenço et al[11]	2015	F	17 d	Multiple lesions with fracture in left ulna	Multiple organs involved, Café-au-lait pigmentation, mosaic GNAS gene mutation	Metyrapone therapy for Cushing syndrome	Cushing syndrome recovered. Death due to respiratory infection
The current case		F	27	Left ischium, left distal fibula, calcaneus, and talus	Discontinuous lesions, intractable bone pain, Cushing syndrome	Diphosphate therapy	Still severe pain. Difficulty participating in daily life and job

M: Male; F: Female.

Table 3 Result of the boosted whole exome screening

Gene	Function of the protein coded	Mutation	Source	Associated disease
RIMS1	A RAS gene superfamily member that regulates synaptic vesicle exocytosis	Point mutation Thr1047His	Maternal, heterozygous	Cone-rod dystrophy type 7
HSPG2	Perlecan that is found in the extracellular matrix	Point mutation Asp2305Asn	Maternal, homozygous	S-J syndrome type 1
APC	Negative regulator of β-catenin/Wnt pathway	Point mutation Lys1586Met	Maternal, heterozygous	Colorectal cancer associated with FAP
BGN	A member of the SLRP family	Point mutation p.Asp168Glu	Maternal, heterozygous	SPD X-linked MLS
BMPR1B	Transmembrane serine/threonine kinases involving TGF-β pathway	Point mutation Met301Val	Maternal, heterozygous	Pulmonary arterial hypertension
CC2D2A	Play a critical role in cilia formation	Point mutation Gly317Arg	Maternal, heterozygous	Meckel syndrome type 6. Joubert syndrome type 9
CDH23	Cadherin superfamily involved in stereocilia organization and hair bundle formation	Point mutation Asp168Glu	Spontaneous, heterozygous	Breast cancer
CHD7	Protein that contains several helicase family domains	Point mutation Asp1486Gly	Spontaneous, heterozygous	CHARGE syndrome
FLNA	An actin-binding protein that crosslinks actin filaments and links actin filaments to membrane glycoproteins	Point mutation Asp1314Asn	Maternal, heterozygous	Several syndromes including PNH, OPDS, FMD and so on
CILK1	Eukaryotic protein kinases	Point mutation Val215Met	Maternal, homozygous	ECD

ECD: Endocrine-cerebroosteo-dysplasia; FAP: Family adenous polyps; FMD: Frontometaphyseal dysplasia; MLS: Meester-Loeys syndrome; OPDS: Otopalatodigital syndromes; PNH: Periventricular nodular heterotopias; SJS: Schwartz-Jampel syndrome; SLRP: Small leucine-rich proteoglycan; SPD: Spondyloepimetaphyseal dysplasia; TGF-β: Transforming growth factor beta.