Neurodevelopmental disorder and juvenile-onset tics associated with microdeletion of the SRRM2 gene

SRRM2-related neurodevelopmental disorder is a recently described genetic diagnosis caused by loss-of-function variants. The clinical presentation is characterised by a developmental delay with mild intellectual disability, occasionally associated with features of autism spectrum disorder and/or attention-deficit/hyperactivity disorder, as well as inconsistent dysmorphic features, hypotonia, and obesity.

We document the rare case of a 30-year-old man diagnosed with neurodevelopmental disorder and juvenile-onset tics associated with a microdeletion involving the SRRM2 gene. He initially presented with simple motor and vocal tics in early adulthood and subsequently developed handwriting tics and limb posturing (catatonic tics). Tic severity was rated as moderate-to-marked (Yale Global Tic Severity Scale score of 55/100) and treatment recommendations included alpha-2 agonists.

To date, a total of 37 cases presenting with loss-of-function mutations in SRRM2 have been reported as neurodevelopmental disease-causing mutations. Of these, 21 were males and none had tics as part of their neurodevelopmental manifestations. Our case report widens the spectrum of neurodevelopmental disorders observed in the context of SRRM2 gene microdeletions and prompts further research to disentangle the contributions of genetic and environmental factors to variable phenotypic expressions.