Abnormal Genetic Testing in Males With Concomitant Neurodevelopmental Disabilities and Genital Malformation

Neurodevelopmental disorders (NDDs) affect 1:6 children in the United States and are often linked to genetic disorders. Because many genes are enriched in brain and testicular tissue, genital malformations identified early may be a predictor of genetic disorders in children with NDDs. However, few studies have evaluated the specific effects of genital malformations. This study assesses the association between genital malformations and abnormal genetic testing among male patients with NDD.

A retrospective chart review was performed of 447 male patients seen at Children's Health Dallas (2009 to 2019) with concomitant genital malformations and NDDs. We assessed the strength of factors associated with obtaining a genetic test and having abnormal results.

We identified 447 patients with concomitant genital malformations and NDD. Fifty-six percent (251 of 447) received genetic testing, of which 68.5% (172 of 251) had abnormal results. Patients with mixed genitourinary malformations, global developmental delay (GDD), intellectual delay, or autism spectrum disorder were more likely to have a genetic test. Patients with bilateral testicular involvement, GDD, severe language delay, wheelchair dependence, or abnormal magnetic resonance imaging findings were more likely to have abnormal results.

The diagnostic yield of 68.5% in our cohort of male patients with genital malformations was higher than previous reports of 5% to 35% in NDD populations. More severe phenotypic features may be associated with increased yield. Identification of genital malformations during infancy may guide clinical surveillance, and copresentations with NDDs may support genetic testing.