2026 Theses Master's

Beyond Childhood: A Conceptual Model of HNRNPH2-Related Neurodevelopmental Disorder in Adolescence and Adulthood

Coker, Caitlin; Mulhern, Maureen S.; Romero, Haylie; Goldman, Jill; Lindig, Angela; Bichell, Terry Jo; Bain, Jennifer M.

Background: HNRNPH2-related Neurodevelopmental Disorder (HNRNPH2-RNDD) is an ultra-rare X-linked condition caused by pathogenic variants in the HNRNPH2 gene. Current literature describes this pediatric-onset condition based on healthcare providers (HCPs) reports, rather than direct reports from individuals with HNRNPH2-RNDD or their caregivers. Furthermore, the existing literature primarily describes pediatric individuals. To bridge this gap, this study is the first to create a disease concept model (DCM) for adolescents and adults with HNRNPH2-RNDD. DCMs are frameworks integrating evidence from published literature and qualitative interviews that create a comprehensive description of a disorder reflective of lived experiences.

Purpose: This study aimed to identify the symptoms and symptom impacts of HNRNPH2-RNDD on the adolescent and adult population and their caregivers to create the first life stage specific HNRNPH2-RNDD DCM.

Methods: We conducted a literature review and 9 semi-structured interviews with caregivers of individuals ≥13 years old with HNRNPH2-RNDD. Interviews were coded using qualitative software and emergent themes were categorized into symptoms, individual impacts, and caregiver impacts.

Results: Speech delay and decreased expressive communication were referenced by all caregivers (9/9, 100%). Other prominent symptoms included skeletal abnormalities (8/9, 88.89%), seizures (7/9, 77.78%), maladaptive behaviors (5/9, 55.56%), and cortical visual impairment (CVI) (3/9, 33.33%). Caregivers referenced the behavioral, communication, emotional, and genitourinary domains more frequently with the 18-29 and 30+ age groups compared to the 12-18 age group. Individual impacts of HNRNPH2-RNDD referenced by the most caregivers included impacts on overall health, activities of daily living, and social engagement. Commonly referenced caregiver impacts were consequences of the diagnostic journey and burdens associated with caregiving. Caregivers described challenges transitioning to adulthood including a lack of available or appropriate HCPs, financial/legal responsibilities, and emotional impacts.

Conclusions: This study presents the first patient-centered DCM focused on adolescents and adults with HNRNPH2-RNDD and their caregivers, highlighting symptom domains that are relevant during the transition to adulthood as well as identifying individual and caregiver impacts of the condition. These results emphasize the need for improved transition support and can be used to develop meaningful interventions, such as clinical trial outcomes, that focus on the primary challenges of the aging HNRNHP2-RNDD population.

Keywords: HNRNHP2-Related Neurodevelopmental Disorder; neurodevelopmental disorder; adolescence; adulthood; transition to adulthood; caregiver perspective; genetics; autism; intellectual disability