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

Area of Science:

• Pediatric Genetics
• Neurodevelopmental Disorders
• Urology

Background:

• Neurodevelopmental disorders (NDDs) affect 1 in 6 children, often linked to genetic causes.
• Genes implicated in NDDs are frequently found in brain and testicular tissue.
• Genital malformations may serve as early indicators of underlying genetic disorders in children with NDDs.

Purpose of the Study:

• To assess the association between genital malformations and abnormal genetic testing in male patients with NDDs.
• To determine the diagnostic yield of genetic testing in this population.

Main Methods:

• Retrospective chart review of 447 male patients with NDDs and genital malformations.
• Analysis of factors associated with genetic testing and abnormal results.

Main Results:

• 68.5% of tested patients (172/251) had abnormal genetic test results.
• Mixed genitourinary malformations, global developmental delay (GDD), intellectual delay, and autism spectrum disorder were associated with higher likelihood of genetic testing.
• Bilateral testicular involvement, GDD, severe language delay, wheelchair dependence, and abnormal MRI findings predicted abnormal genetic test results.

Conclusions:

• The diagnostic yield of 68.5% in this cohort exceeds previous reports (5-35%) for NDD populations.
• More severe phenotypic features correlate with increased genetic testing yield.
• Identifying genital malformations in infancy can guide surveillance and support genetic testing in NDD patients.