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

Abstract

Background: Xia–Gibbs syndrome (XGS) is a rare disorder caused by de novo mutations in the AT-Hook DNA binding motif Containing 1 (AHDC1) gene, which is characterised by a wide spectrum of clinical manifestations, including global developmental delay, intellectual disability, structural abnormalities of the brain, global hypotonia, feeding problems, sleep difficulties and apnoea, facial dysmorphisms, and short stature. Methods: Here, we report on a girl patient who shows a peculiar cognitive and behavioural profile including high-functioning autism spectrum disorder (ASD) without intellectual disability and provide information on her developmental trajectory with the aim of expanding knowledge of the XGS clinical spectrum. On the basis of the current clinical case and the literature review, we also attempt to deepen understanding of behavioural and psychiatric manifestations associated with XGS. Results: In addition to the patient we described, a considerable rate of individuals with XGS display autistic symptoms or have been diagnosed with an autistic spectrum disorder. Moreover, the analysis of the few psychopathological profiles of patients with XGS described in the literature shows a frequent presence of aggressive and self-injurious behaviours that could be either an expression of autistic functioning or an additional symptom of the ASD evolution. A careful investigation of the abovementioned symptoms is therefore required, since they could represent a “red flag” for ASD.

Novel Insights from Clinical Practice: Xia-Gibbs Syndrome with Pes Cavus, Conjunctival Melanosis, and Eye Asymmetry due to a de novo AHDC1 Gene Variant – A Case Report and a Brief Review of the Literature

“…The most frequent features include facial dysmorphisms, developmental delay with intellectual disability and/or language delay, hypotonia, structural anomalies of the brain such as thin corpus callosum, epilepsy, behavioral abnormalities, strabismus, and abnormalities of refraction. Our review confirms a significant prevalence of neurodevelopmental disorders and psychiatric problems among patients with Xia-Gibbs syndrome, as recently suggested by Della Vecchia et al [2021]. By reviewing all the pictures and data of the patients reported in the literature and comparing them with our patient, we noticed that eye asymmetry may be observed in some individuals.…”

Genotype–phenotype spectrum and correlations in Xia‐Gibbs syndrome: Report of five novel cases and literature review

“…Patient 2 also lacked neonatal hypotonia, specific neuroimaging abnormalities, and ataxia. However, he presented with seizures, which are reported in 34% of XGS patients (Della Vecchia et al, 2021). Atypical osteoarticular manifestations and scoliosis were observed in 4/5 of our patients: hammerfirst fingers in patient 1; joint laxity, reduction of physiological spinal curvatures, coxa vara and phalangeal abnormalities in patient 3; hallux valgus with cone‐shaped epiphysis of the proximal phalanx of toes in patient 4; flat feet in patient 5.…”

“…Sagittal 3D‐T1‐weighted images at 3 months (c) and 3 years old (d). (c) Summary of the main neurological features of XGS (adapted from Della Vecchia) (Della Vecchia et al, 2021). P = patient…”