Are genetic problems causes of autism in children? An etiological spectrum of secondary causes of autism spectrum disorder (ASD) – A retrospective study

Dear Editor,

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, with a prevalence estimated to be 0.0014 − 0.0012%.^[1] Genetic testing has yielded a diagnostic yield of up to 30% with the use of exome or genome sequencing, making the latter the first tier of investigation in this group.^[2] We aim to determine the aetiological spectrum of genetically proven causes using various molecular techniques, including chromosomal microarray, methylation studies, fragile X screening, and exome sequencing, as indicated clinically, among children with ASD. Included variants that were pathogenic/likely pathogenic only.

This is a retrospective chart review of all cases diagnosed as ASD (using the modified checklist for autism in toddlers, revised [MCHAT-R]) with positive genetic testing reports from the past 3 years at the paediatric neurology clinic. Out of 136 children, 79 were male (58%) with a mean age of 6 years (Standard deviation = 4.2). Monogenic disorders constituted 123 (90.5%): autosomal dominant disorders were most common - 58 (42.5%), followed by recessive disorders in 34 (25%) and X-linked inheritance in 31 (23%), chromosomal disorders - 10 (7.35%) and Fragile X syndrome constituted - 3 (2%) cases.

The common cause in females was Rett syndrome (37%), while it was non-syndromic monogenic in males (26%). Chromosomal defects included Angelman syndrome and Prader–Willi syndrome (10%). Monogenic syndromic causes include Mucopolysaccharidosis type 3 (11%), Coffin–Siris syndrome (10%), cerebral creatine deficiency (8%), neurofibromatosis 1 (5%), mucolipidosis (4%), tuberous sclerosis (4%), fragile X syndrome, and phenylketonuria (3%). Co-morbidities were global developmental delay (79%), seizures (45%), dysmorphism (44%), tone abnormalities 46% and microcephaly (32%).

Sheth et al. identified the aetiology in 30% of cases.^[2] Sánchez Suárez et al. showed an overall diagnostic yield of 3.2% in autism and 12.7% in children with both autism and developmental delay.^[3] Similar findings were noted in the current study. To conclude, exome sequencing is a helpful test that can detect most of the known aetiologies in children with autism.