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.

Keywords: Xia–Gibbs syndrome; autism spectrum disorder; genetic autism.

Figure 1

Brain MRI of a 3.5-year-old girl. Sagittal (A) and axial T2 weighted images (B) show enlarged retrovermian cistern and left pericerebellar subarachnoid space (black and white arrowheads). Sagittal T1 weighted image (C) shows thinning of the isthmus of the corpus callosum (white arrow). Sagittal (A,C) and axial (D) images show a normal conformation of the cerebellar hemispheres and vermis. MRI remained unchanged in comparison with the previous one performed at the age of 2.4 years old, except for a progression of the myelination.

Figure 2

PRISMA flow diagram of search yield, screening and inclusion steps.

Figure 3

Bar graph showing XGS clinical phenotypes in 67 patients from the literature. Comparison between literature data (on the left), and our case (on the right). Y: yes. N: not present.

Figure 4

XGS neuroradiological findings in patient from the literature. Among a total of 63 patients with at least one brain MRI, 19 exhibited normal and 44 abnormal findings (pie chart). A detailed description of the literature brain MRI findings was only available for 31 of the 44 patients with abnormal findings in neuroimaging (bar graph). On the right-hand side, a comparison of our patient with literature data. Y: yes. N: not present.