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.
Highlights
BackgroundXia-Gibbs syndrome (XGS) is a rare genetic disorder that occurs due to a heterozygous truncating mutation of a gene on chromosome 1p36 [1,2]
In 2015, whole-exome sequencing (WES) testing was performed on more than 2000 patients who presented with developmental delay (DD) and/or intellectual disability (ID) by Yang et al They identified mutations same as those found by Xia et al in seven patients [2]
We recommend delving into the part played by the AT-Hook deoxyribonucleic acid (DNA) binding motif Containing 1 (AHDC1) gene in humans to establish links with neurocognitive development in persons affected with XGS
Summary
Xia-Gibbs syndrome (XGS) is a rare genetic disorder that occurs due to a heterozygous truncating mutation of a gene on chromosome 1p36 [1,2]. On performing genetic tests by whole-exome sequencing (WES) in four patients with clinical features of intellectual impairment, low tone, dysmorphic facies, delayed language development, and sleep issues, they found a new, dominant, monoallelic mutation of the AHDC1 gene [1]. In 2015, WES testing was performed on more than 2000 patients who presented with developmental delay (DD) and/or intellectual disability (ID) by Yang et al They identified mutations same as those found by Xia et al in seven patients [2] These seven patients were diagnosed with XGS due to similar clinical findings. They attributed haploinsufficiency of 1p36.11 situated in the AHDC1 gene as the cause of XGS because it encodes a protein made of 1603 amino acids [2,5]. Parents of children with XGS should be prompted for regular physiotherapy for gain in function
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