Autism is defined as a pervasive developmental disorder characterized by the triad of limited verbal communication, absence of social responsiveness and stereotypic, ritualized patterns of behavior. Individuals with AUTS18 also suffer from macrocephaly, intellectual disability, seizures, regression, sleep disturbances, gastrointestinal problems and constipation. They are generally of tall stature and exhibit facial dysmorphia such as supraorbital ridges and down-slanting palpebral fissures. The overall rate of incidence for Autism Spectrum Disorder is about 6 in 1000 individuals. Males are more frequently affected by autism than females, with a ratio of 4.2:1. AUTS18 is a rare subset of Autism, with only a handful of cases reported thus far.
Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Instrument (ADI) are considered the gold standards of assessment tools used for autism diagnosis. While there is currently no cure for the condition, several therapies exist to alleviate symptoms. Patients benefit from early intervention and behavioral therapy. Medications are also available to help treat anxiety, attention problems, repetitive behavior and hyperactivity.
The condition follows an autosomal dominant pattern of inheritance and is caused by mutations in the CHD8 gene. This gene encodes a helicase enzyme that functions as a chromatin remodeling factor and transcription regulator. It thus plays a key role in the regulation of the Wnt signalling pathway, the fibroblast apoptotic process, and in-utero embryonic development. More than 30 CHD8 gene mutations have been associated with autism spectrum disorder, including indels, splice site variants and nonsense mutations.
Monies et al. (2017) reported the findings of 1000 diagnostic panels and exomes carried out at a next generation sequencing lab in Saudi Arabia. One patient, a 6-year-old male from a consanguineous family, presented with fine/gross motor delay, speech delay, learning disability, developmental regression and autistic features. Using whole exome sequencing, a heterozygous mutation (4984C>T, p.R1662X) was identified in exon 26 of the patient’s CHD8 gene. As the gene had previously been tentatively linked to Autism, this finding helped confirm its association with the disorder.
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