Neurodevelopmental and neurological features in children with hypochondroplasia

To assess neurodevelopmental and neurological features, including neuroimaging abnormalities, in children with molecularly confirmed hypochondroplasia.

A retrospective cohort study of children with molecularly confirmed hypochondroplasia seen at Evelina London Children's Hospital skeletal dysplasia service was performed. Data collected included referral characteristics, neuroimaging findings, special educational needs, and diagnosed neurodevelopmental disorders. Statistical comparisons with UK population prevalence were performed using χ² testing for educational outcomes and exact binomial testing for neurodevelopmental disorders, with Bonferroni-adjusted p-values reported for multiple comparisons.

Forty-four children (24 females and 20 males; median age 9 years 10 months [interquartile range 6 years 7 months-15 years 7 months]) with molecularly confirmed hypochondroplasia were included. Twenty-five had received brain imaging with hippocampal malrotation (HIMAL) identified in 23 (92%). Among school-aged children, 71% required special educational support and 29% had formal education, health, and care plans (EHCPs), statistically higher than both UK population prevalence and previously reported hypochondroplasia prevalence. Formally diagnosed neurodevelopment disorders affected 20.5% of the cohort. Specific learning disorders remained significantly more common than UK population prevalence estimates after Bonferroni correction, with higher observed autism and attention-deficit/hyperactivity disorder rates also identified.

Hypochondroplasia is associated with a substantial burden of neurodevelopmental and neurological abnormalities, including a high prevalence of HIMAL, which exceeds previous estimates. These findings support the need for clinical guidelines, developmental surveillance, and further research into fibroblast growth factor receptor 3 (FGFR3)-related brain development.