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Variable Clinical Manifestations of Xia‐Gibbs syndrome: Findings of Consecutively Identified Cases at a Single Children's Hospital
Author(s) -
Ritter Alyssa L.,
McDougall Carey,
Skraban Cara,
Medne Livija,
Bedoukian Emma C.,
Asher Stephanie B.,
Balciuniene Jorune,
Campbell Colleen D.,
Baker Samuel W.,
Denenberg Elizabeth H.,
Mazzola Sarah,
Fiordaliso Sarah K.,
Krantz Ian D.,
Kaplan Paige,
IerardiCurto Lynne,
Santani Avni B.,
Zackai Elaine H.,
Izumi Kosuke
Publication year - 2018
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.40380
Subject(s) - medicine , pediatrics , exome sequencing , hypotonia , dermatology , genetics , mutation , gene , biology
Xia‐Gibbs syndrome (XGS) is a recently described neurodevelopmental disorder due to heterozygous loss‐of‐function AHDC1 mutations. XGS is characterized by global developmental delay, intellectual disability, hypotonia, and sleep abnormalities. Here we report the clinical phenotype of five of six individuals with XGS identified prospectively at the Children's Hospital of Philadelphia, a tertiary children's hospital in the USA. Although all five patients demonstrated common clinical features characterized by developmental delay and characteristic facial features, each of our patients showed unique clinical manifestations. Patient one had craniosynostosis; patient two had sensorineural hearing loss and bicuspid aortic valve; patient three had cutis aplasia; patient four had soft, loose skin; and patient five had a lipoma. Differential diagnoses considered for each patient were quite broad, and included craniosynostosis syndromes, connective tissue disorders, and mitochondrial disorders. Exome sequencing identified a heterozygous, de novo AHDC 1 loss‐of‐function mutation in four of five patients; the remaining patient has a 357kb interstitial deletion of 1p36.11p35.3 including AHDC1 . Although it remains unknown whether these unique clinical manifestations are rare symptoms of XGS, our findings indicate that the diagnosis of XGS should be considered even in individuals with additional non‐neurological symptoms, as the clinical spectrum of XGS may involve such non‐neurological manifestations. Adding to the growing literature on XGS, continued cohort studies are warranted in order to both characterize the clinical spectrum of XGS as well as determine standard of care for patients with this diagnosis.