Inherited and de novo variants extend the etiology of TAOK1 -associated neurodevelopmental disorder.

Alterations in the gene have recently emerged as the cause of developmental delay with or without intellectual impairment or behavioral abnormalities (MIM # 619575). The 32 cases currently described in the literature have predominantly de novo alterations in and a wide spectrum of neurodevelopmental abnormalities. Here, we report four patients with novel pathogenic variants identified by research genome sequencing, clinical exome sequencing, and international matchmaking. The overlapping clinical features of our patients are consistent with the emerging core phenotype of -associated syndrome: facial dysmorphism, feeding difficulties, global developmental delay, joint laxity, and hypotonia. However, behavioral abnormalities and gastrointestinal issues are more common in our cohort than previously reported. Two patients have de novo variants (one missense, one splice site) consistent with most known alterations in this gene. However, we also report the first sibling pair who both inherited a frameshift variant from a mildly affected mother. Our findings suggest that incomplete penetrance and variable expressivity are relatively common in -associated syndrome, which holds important implications for clinical genetic testing.