Xia-Gibbs Syndrome: A Review of Literature

Abstract

Xia-Gibbs syndrome (XGS) is a rare genetic disorder that has been discovered as a distinct clinical entity in the recent past. The occurrence has been attributed to the mutation of AT Hook DNA binding motif Containing 1 (AHDC1) gene that is carried on chromosome 1p36. The concerned gene participates in deoxyribonucleic acid (DNA) repair apart from other crucial functions. The mutation results in dysfunction that leads to neurodevelopmental delay. The spectrum of manifestations constitutes intellectual disabilities, hypotonia, expressive language delay, sleep difficulties, and short stature. Dysmorphic facial features include depressed nasal bridge, hypertelorism, down-slanting or up-slanting palpebral fissures, horizontal eyebrows, dysplastic dentition, thin upper lip vermilion, and micrognathia. The phenotype is still expanding. The condition may range from mild to severe dysfunction depending on the area and site of genetic aberration but variation is evident. Thus, the correlation between genotype and phenotype is largely unclear. XGS should be considered as a differential diagnosis for patients presenting with intellectual as well as developmental disabilities. Whole-exome sequencing (WES) is the genetic test that is largely used for the confirmation of diagnosis. Less is known about the natural history as only a few adults with XGS have been documented in the literature. Age-appropriate cancer screening is recommended for patients with XGS as the gene mutation alters DNA repair mechanisms that may trigger tumour formation. The management of patients diagnosed with XGS is an area that needs investigation. Though use of growth hormone replacement therapy and physiotherapy intervention have been reported as effective in previous studies, research on effective means of care of these patients is warranted on a larger number of patients. We present a review of current literature on what is known about XGS that would facilitate to identify knowledge gaps for paving a way for further studies. This, in turn, will help in provision of early and effective rehabilitation services for patients with XGS.

A Rare and Unusual Case of Trisomy 10p with Terminal 14q Deletion: A Multidisciplinary Approach

“…GMFM-88 was used for the evaluation of motor skills because its reliability and validity have been established for conditions other than cerebral palsy [ 6 , 7 ]. Physiotherapy management of children with genetic syndromes with tonal abnormalities based on the principles of neurodevelopmental treatment and sensory integration has also been found to be helpful in the literature in improving sensory-motor function [ 17 - 19 ]. Vestibular input helped in improving modulation and in reducing extraneous movements as was observed in former studies on varied causes of developmental delays [ 18 , 20 ].…”

Focusing on Autism Spectrum Disorder in Xia–Gibbs Syndrome: Description of a Female with High Functioning Autism and Literature Review

“…Xia-Gibbs syndrome (XGS) is a rare disorder discovered in the last decade caused by de novo mutations within a critical region of the AT-Hook DNA Binding Motif Containing 1 (AHDC1) gene, identified performing whole-exome sequencing. AHDC1 function is still not fully understood: it may be involved in DNA repair as well as epigenetic and transcriptional regulation during axon genesis, with potential consequences on neurodevelopment [1].…”

“…This syndrome is characterized by global development delay, intellectual impairment, structural anomalies of the brain, global hypotonia, feeding issues, sleep difficulties and apnoea, facial dysmorphisms, and short stature [1,2].…”

“…Since its discovery in 2014 [3], approximately 250 cases of XGS have been reported until now, although the prevalence of this syndrome may be underestimated because of its phenotypic variability [1]. For this reason, the wide phenotypic spectrum of the syndrome has entailed molecular diagnosis as the primary diagnostic tool for XGS, instead of the recognition of distinctive facial dysmorphisms, or a facial gestalt.…”

“…For this reason, the wide phenotypic spectrum of the syndrome has entailed molecular diagnosis as the primary diagnostic tool for XGS, instead of the recognition of distinctive facial dysmorphisms, or a facial gestalt. However, facial features are peculiar and include broad forehead, horizontal eyebrows, hypertelorism, down-or Children 2021, 8, 450 2 of 13 up-slanting palpebral fissures, depressed nasal bridge, thin upper lip, dysplastic dentition, and micrognathia [1,4].…”