Childhood motor speech disorders: who to prioritise for genetic testing

The aetiology of childhood motor speech disorders of dysarthria and apraxia has been poorly understood. Recent evidence suggests a moderate genetic contribution for these rare and severe speech disorders. To date, however, no studies have examined genetic diagnostic yield for childhood apraxia of speech (CAS) and dysarthria in a clinical setting. Here, we used a clinically accredited genomics pipeline to investigate genetic diagnostic yield and variables predictive of a genetic diagnosis in a tertiary hospital speech clinic. A cohort of 153 children (range 2;7-16;5 years, 42 female) ascertained for motor speech disorder were assessed by a clinical geneticist and speech pathologist and underwent chromosomal microarray, Fragile X and exome sequencing. Odds ratios identified predictors of genetic diagnosis. 44/153 (29%, 15 female) had pathogenic variants (30 de novo), encompassing monogenic conditions (n = 35) and copy number variants (n = 9) across 38 distinct disorders. Delayed walking, fine and gross motor disorder, receptive language impairment and/or cognitive impairment, and dysmorphism were associated with a genetic diagnosis. The presence of CAS and dysarthria was more commonly associated with a genetic diagnosis than CAS alone. Autism spectrum disorder was less commonly associated with a genetic diagnosis. No child had a Fragile X diagnosis. The clinical genetic diagnostic yield for motor speech disorders is comparable to epilepsy and cerebral palsy, conditions where genetic testing is routine in most centres, unlike for motor speech disorders. Children with motor speech disorder with co-occurring motor, language and/or learning deficits, should be prioritised for genomic testing.