Natural history of hypochondroplasia: A retrospective, matched-cohort study using the Clinical Practice Research...

Hypochondroplasia is a rare genetic condition that causes disproportionate short stature. This retrospective, real-world, matched-cohort study used electronic health records data from the Clinical Practice Research Datalink Aurum primary care database, linked to Hospital Episode Statistics and Office of National Statistics mortality records, to assess the natural history of hypochondroplasia in England from 1998 to 2019. A total of 549 participants with hypochondroplasia and 2196 matched controls were included. Mean follow-up time was 7.50 years for participants with hypochondroplasia and 11.68 years for controls. Approximately 60% of participants were aged >18 years at start of follow-up. Mean age (standard deviation) at first recorded hypochondroplasia code was 29.20 (20.2) years. The highest event rates for participants with hypochondroplasia involved cardiovascular, orthopaedic, respiratory, mental health, and ear, nose and throat (ENT) systems. Event rates for the selected comorbidities combined were higher in participants with hypochondroplasia versus controls (rate ratio [RR] 2.13, 95% confidence interval [CI] 1.98-2.28). Participants with hypochondroplasia had higher healthcare visit rates, including a median of 10.91 annual general practitioner visits versus 5.52 for controls (RR 1.63, 95% CI 1.48-1.80). Mortality rates were more than double for participants with hypochondroplasia versus controls (RR 2.64, 95% CI 1.33-5.26), mainly driven by cohorts aged ≥30 years and by cardiovascular and respiratory diseases. Rates for procedures, particularly orthopaedic and ENT, and medication use were also higher among participants with hypochondroplasia versus controls. These results highlight the medical burden of hypochondroplasia and need for coordinated, multidisciplinary management starting early in life.