Xia-Gibbs syndrome in adulthood: a case report with insight into the natural history of the condition

• Published in: Cold Spring Harbor molecular case studies 2019-06, Vol.5 (3), p.a003608
• Main Authors: Murdock, David R, Jiang, Yunyun, Wangler, Michael, Khayat, Michael M, Sabo, Aniko, Juusola, Jane, McWalter, Kirsty, Schatz, Krista Sondergaard, Gunay-Aygun, Meral, Gibbs, Richard A
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - genetics; Abnormalities, Multiple - pathology; Case reports; DNA microarrays; Exome Sequencing; Gene sequencing; Heterozygote; Humans; Intellectual disabilities; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Intellectual Disability - pathology; Kyphosis; Male; Middle Aged; Mitochondria; Natural history; Phenotypes; Research Report; Scoliosis
• ISSN: 2373-2865; 2373-2873; 2373-2873
• DOI: 10.1101/mcs.a003608

A 55-yr-old male with severe intellectual disability, behavioral problems, kyphoscoliosis, and dysmorphic features was referred for a genetic evaluation. Chromosomal microarray, RASopathy gene panel, mitochondrial sequencing, and fragile X testing were all negative. Subsequent whole-exome sequencing revealed a heterozygous, truncating variant in the gene, consistent with a diagnosis of Xia-Gibbs syndrome (XGS). Review of his clinical history showed many classic dysmorphic and clinical features of XGS, but no major health issues in adulthood other than intellectual disability. This individual is the oldest published XGS case to date, demonstrates the wide phenotypic spectrum of the disorder, and provides information on the condition's natural history. As more adults undergo genomic studies, we will continue to learn about the adult phenotypes of genetic conditions typically diagnosed in the pediatric setting.