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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Mosaicism of a novel variant in the ANKRD11 gene in a child with a mild KBG phenotype: A case report
Roberto Franceschi, Francesca Rivieri, Antonio Novelli, Daniele Ferretti, Adriano Anesi, Massimo Soffiati, Giulia Porretti, Evelina Maines, Mafalda Mucciolo, Giorgio Radetti
Roberto Franceschi, Department of Pediatrics, S. Chiara Hospital of Trento, APSS, Trento 38122, Italy
Francesca Rivieri, Adriano Anesi, Genetic Unit, Laboratory of Clinical Pathology, Department of Laboratories, APSS, Trento 38122, Italy
Antonio Novelli, Laboratory of Medical Genetics, Ospedale Pediatrico Bambino Gesù, Rome 00165, Italy
Daniele Ferretti, Mafalda Mucciolo, Human Genetics Laboratory, Ospedale Pediatrico Bambino Gesù, Rome 00165, Italy
Massimo Soffiati, Evelina Maines, Department of Pediatrics, S. Chiara General Hospital, APSS, Trento 38122, Italy
Giulia Porretti, Department of Radiology, S. Chiara General Hospital, APSS, Trento 38122, Italy
Giorgio Radetti, Department of Pediatrics, General Hospital Bolzano, Marienklinik, Bolzano 39100, Italy
Author contributions: Franceschi R, Rivieri F, Maines E, Anesi A, Soffiati M, Porretti G, and Radetti G followed the patient up; Novelli A, Ferretti D and Mucciolo M performed the genetic test; Franceschi R, Radetti G, Maines E and Mucciolo M drafted the manuscript; All authors critically reviewed and edited the manuscript, and approved the final version as submitted.
Informed consent statement: Informed written consent was obtained from the father of the patient for publication of this report. The father refused consent to publish child’s picture.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Evelina Maines, MD, Department of Pediatrics, S. Chiara Hospital, Largo Medaglie d’Oro, 9, Trento 38122, Italy. evelina.maines@apss.tn.it
Received: February 6, 2023
Peer-review started: February 8, 2023
First decision: April 28, 2023
Revised: May 3, 2023
Accepted: May 19, 2023
Article in press: May 19, 2023
Published online: June 2, 2023
Processing time: 115 Days and 18.7 Hours
BACKGROUND
KBG syndrome is likely underdiagnosed because of mild and non-specific features in some affected patients especially before the upper permanent central incisors eruption at about the age of 7-8 years. Somatic mosaicisms are usually recognized in the parents only after a typically affected son is diagnosed with KBG syndrome. We describe for the first time the mosaicism of a novel variant in a child with a mild KBG phenotype.
CASE SUMMARY
Our patient presented at 24 mo of age with short stature, hand abnormalities, facial dysmorphism and mild developmental delay. Pituitary hypoplasia and central hypothyroidism were also detected. By next generation sequencing (NGS) analysis we found a novel deletion in the ANKRD11 gene (c.4880_4893del.), that can be classified as likely pathogenic for the syndrome, with the percentage of mutated allele of 36%. We considered this finding as causative of the mild and non-specific phenotype for KBG syndrome in our patient, as previously reported in adults. A heterozygous variant in HESX1 gene, classified as variant of uncertain significance, but suspected of causing pituitary hypoplasia and hormonal deficiency, was also found. The patient started levothyroxine and growth hormone treatment.
CONCLUSION
The increased use of NGS analysis may expand the phenotypic spectrum of KBG syndrome because it allows genetic diagnosis of somatic mosaicisms also in children.
Core Tip: Somatic mosaicisms of KBG syndrome are usually recognized in the parents only after a typically affected son is diagnosed. We report for the first time the case of a somatic mosaicism for KBG syndrome diagnosed in a child with a mild and non-specific phenotype. The increased use of next generation sequencing allows a genetic diagnosis of this mosaic form in children expanding the phenotypic spectrum of the KBG syndrome.
