Peer-reviewed article
Neurodevelopmental and neurological features in children with hypochondroplasia.
Baxter MF, Akilapa R, Cocca A, Irving MD ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This study examined neurodevelopmental and neurological features in 44 children with hypochondroplasia, a genetic skeletal disorder. Most children who received brain imaging showed hippocampal malrotation, and over 70% of school-aged children needed special educational support. The study found higher rates of learning disorders, autism, and attention problems compared to the general UK population, suggesting hypochondroplasia significantly affects child development and learning.
Key points
- 92% of 25 children who underwent brain imaging showed hippocampal malrotation (HIMAL)
- 71% of school-aged children required special educational support
- 29% had formal education, health, and care plans, higher than UK population prevalence
- 20.5% had formally diagnosed neurodevelopmental disorders
- Specific learning disorders remained significantly more common than UK population estimates after statistical adjustment
Limitations
This is a retrospective cohort study from a single specialist centre in the UK, so findings may not generalise to other populations or settings. The study does not establish causation or explain the mechanisms by which hypochondroplasia affects neurodevelopment.
Abstract
Aim To assess neurodevelopmental and neurological features, including neuroimaging abnormalities, in children with molecularly confirmed hypochondroplasia. Method 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. Results 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. Interpretation 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.