Introduction:

Autism spectrum disorder (ASD) is one of the most complex behavioral disorders with a strong genetic influence.

Methods:

The current study was carried out in a tertiary care center in North India to determine the yield of genetic tests in children with ASD diagnosed between January 2017 and May 2018. Initially directed genetic testing for clinically suspected monogenic syndromes like Fragile X, Rett and Angelmann syndrome, Neurofibromatosis and Tuberous Sclerosis was done. Subsequently Karyotyping followed by Chromosomal Microarray ( in children with dysmorphism, epilepsy, multiple congenital anomalies and history of recurrent abortions) and finally whole exome sequencing by next generation sequencing (NGS) was done. Metabolic testing was done in children with global regression, recurrent encephalopathy, refractory seizures and consanguinity.

Results:

Out of 318 children (223 boys, 70%; 5.2+/-1.3 years) diagnosed with ASD during study period, 32 (10 %) were found to have genetic cause. 20 children (6%) had monogenic syndromes {Tuberous Sclerosis (n=8), Fragile X syndrome (n=5), Rett Syndrome (n=4),Angelmann Syndrome(n=2)and  Neurofibromatosis(n=1)}. Abnormal karyotype and pathogenic copy number variants were found in 4 and 5 children respectively (3 childrenhad 21 trisomy). NGS detected pathogenic mutations in 2 children with epilepsy(STXBP1 and GRIN2A genes). One child with autistic regression and epilepsy was found to haveLate Infantile Neuronal Ceroid Lipofuscinosis. The impact on clinical management included: disease monitoring (n=10), investigation for systemic involvement (n=7), reproductive planning (n=6), and prognostication(n=1).

Conclusion:

Appropriate clinical suspicion and stepwise judicious genetic testing can help in detecting underlying genetic causes in autistic children.