Case report of a girl with HNRNPH2-related neurodevelopmental disorder

We present a 3-year-old female patient with global developmental delay. The expressive language is limited to very few spoken words and the patient shows profound motor impairment, the highest achieved motor milestone being independent sitting and cautious bottom shuffling. The patient presented with short stature (1st percentile, −2.25 SD), low body weight (<1st percentile, −2.76 SD), and microcephaly (head circumference <1st percentile, −3.09 SD). Additional neurological findings include muscular hypotonia, joint hypermobility, and equinus foot deformity requiring ankle orthoses. Further clinical features comprised alternating divergent strabismus, selective hyperacusis, and a history of neonatal apnea. Family history is unremarkable. Trio-genome-sequencing identified a de novo heterozygous pathogenic variant in HNRNPH2 (NM_019597.5:c.616C>T p.(Arg206Trp)). The HNRNPH2-related neurodevelopmental disorder is an extremely rare disease with less than 200 known cases. The phenotype of the presented patient is highly consistent with HNRNPH2-related neurodevelopmental disorder, however facial features of HNRNPH2-related neurodevelopmental disorder are considered nonspecific at this point. A targeted antisense oligonucleotide (ASO) therapy for the HNRNPH2-related disorder is currently in development, with the first FDA-approved human clinical trial initiated in July 2024.