714 - First Reported Case of CHD2-Related Neurodevelopmental Disorder in Puerto Rico: Clinical Presentation and Genetic Findings

Case Diagnosis: CHD2-related neurodevelopmental disorder is a rare genetic condition caused by pathogenic variants in the CHD2gene, located on chromosome 15q26.1. Mutations in CHD2 have been associated with a spectrum of neurodevelopmental disorders, including early-onset developmental and epileptic encephalopathy, developmental delay, intellectual disability and autism spectrum disorder.

Case Description: We present the case of a 3-year-old Puerto Rican girl born at 37 weeks’ gestation via cesarean section due to breech presentation and IUGR, with reported decreased fetal movements. She has a history of developmental delay with regression of previously acquired skills.  Now presenting with axial hypotonia, mild appendicular hypotonia, and wide base of support with difficulty with balance and motor control while ambulating unassisted. She is nonverbal and has been diagnosed with autism spectrum disorder (Level 1). She experiences daily myoclonic seizures despite antiepileptic therapy. Additional concerns include intermittent constipation, urinary incontinence, and inability to tolerate oral intake. 

An Epilepsy Comprehensive panel identified a heterozygous likely pathogenic variant in the CHD2 gene (c.1052+2T >C (p.?)), consistent with autosomal dominant inheritance of a CHD2-related condition.

Discussions: To our knowledge, this is the first reported case of CHD2-related neurodevelopmental disorder in Puerto Rico. The patient’s clinical features are consistent with the phenotype typically associated with CHD2-related neurodevelopmental disorders. This case underscores the importance of genetic testing in children with epilepsy and developmental delay, enabling precise diagnosis and guiding care. Documented cases have highlighted frequent presentations of axial and appendicular hypotonia, further impacting motor delays and gait disturbances in these patients.

Conclusions: CHD2-related neurodevelopmental disorder is a rare genetic condition with wide phenotypic variability, including developmental delay, epilepsy, and autism spectrum features. Early diagnosis and interventions with targeted therapies are important in patients presenting with CHD2 related phenotypes, as well as equipment and orthotic recommendations facilitating safe activities and milestone attainment.