{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:50:13Z","timestamp":1788306613457,"version":"build-2803163510"},"reference-count":10,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,8,27]],"date-time":"2018-08-27T00:00:00Z","timestamp":1535328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Xia\u2010Gibbs syndrome (XGS) is a recently described neurodevelopmental disorder due to heterozygous loss\u2010of\u2010function <jats:italic>AHDC1<\/jats:italic> 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, <jats:italic>de novo AHDC<\/jats:italic>1 loss\u2010of\u2010function mutation in four of five patients; the remaining patient has a 357kb interstitial deletion of 1p36.11p35.3 including <jats:italic>AHDC1<\/jats:italic>. 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\u2010neurological symptoms, as the clinical spectrum of XGS may involve such non\u2010neurological 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.<\/jats:p>","DOI":"10.1002\/ajmg.a.40380","type":"journal-article","created":{"date-parts":[[2018,8,28]],"date-time":"2018-08-28T10:54:28Z","timestamp":1535453668000},"page":"1890-1896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Variable Clinical Manifestations of Xia\u2010Gibbs syndrome: Findings of Consecutively Identified Cases at a Single Children's Hospital"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4735-5223","authenticated-orcid":false,"given":"Alyssa L.","family":"Ritter","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics The Children's Hospital of Philadelphia  Pennsylvania Philadelphia 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3064-2488","authenticated-orcid":false,"given":"Emma C.","family":"Bedoukian","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics The Children's Hospital of Philadelphia  Pennsylvania Philadelphia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie B.","family":"Asher","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics The Children's Hospital of Philadelphia  Pennsylvania Philadelphia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorune","family":"Balciuniene","sequence":"additional","affiliation":[{"name":"Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine The Children's Hospital of Philadelphia  Pennsylvania Philadelphia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen 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Pediatrics The Children's Hospital of Philadelphia  Pennsylvania Philadelphia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Fiordaliso","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics The Children's Hospital of Philadelphia  Pennsylvania Philadelphia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian D.","family":"Krantz","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics The Children's Hospital of Philadelphia  Pennsylvania Philadelphia USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania, Philadelphia  Pennsylvania Philadelphia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics The Children's Hospital of Philadelphia  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