Clinical Guidance
Most individuals with HNRNPH2-related neurodevelopmental disorder (HNRNPH2-NDD) have symptoms early in life, before age 12 months. The major features of HNRNPH2-NDD are developmental delay/ intellectual disability, motor and language delays, behavioral and psychiatric disorders, and growth and musculoskeletal abnormalities. Minor features include dysmorphic facies, gastrointestinal disturbances, epilepsy, and visual defects. To date, 49 individuals from 45 families with pathogenic variants in HNRNPH2 have been identified [, , , , , ]. Initially, because the only affected individuals were phenotypic females presumed to be 46,XX, it was hypothesized that affected 46,XY individuals were embryonic lethal. However, at least 16 affected 46,XY individuals have now been reported [, , , , , ]. At least one unaffected mother of an affected female was found to have the same HNRNPH2 pathogenic variant as her daughter. This unaffected mother had significantly skewed X-chromosome inactivation . There is not enough information on affected females versus affected males to make any generalizations about phenotypic differences between the two sexes. Table 2. HNRNPH2-Related Neurodevelopmental Disorder: Frequency of Select Features
Feature | # of Personsw/Feature (%) | Comment |
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