This study aimed to identify the foremost concerns for caregivers of children with HNRNPH2-related neurodevelopmental disorder (NDD).

Rare NDDs are individually rare yet collectively common and are associated with shared challenges for patients and their caregivers. Pathogenic variants in the X-linked gene, HNRNPH2, share a NDD characterized by developmental delay, language impairment, motor problems, autism, and seizures.

Eighty-five individuals with confirmed pathogenic HNRNPH2 variants were enrolled in an annual natural history study of HNRNPH2-related NDD. The caregivers of 41 of these individuals with HNRNPH2-related NDD, aged 12 months old to 53 years old (median=10.2), both females (n=34) and males (n=7), were included. For each participant, one caregiver completed a survey ranking their top concerns from most concerning to least concerning. Responses were compared between the caregivers of adults (n=14) and children (n=27).

We expanded the behavioral and neuropsychiatric spectrum of HNRNPH2-related NDD in the largest cohort described to date. Communication difficulties, behavioral issues, and independence skills were the top caregiver concerns. While caregivers of adults with HNRNPH2-related NDD reported more concerns for communication difficulties, independence skills, and musculoskeletal issues, caregivers of children were most concerned with communication difficulties, seizures, and behavioral issues. Results did not differ substantially for children under 18 years old between age ranges.