Achondroplasia and hypochondroplasia in France: a nationwide epidemiological analysis

Achondroplasia (ACH) and hypochondroplasia (HCH) are among the most common forms of skeletal dysplasia, caused by gain-of-function variants in the FGFR3 gene, leading to disproportionate short stature. The birth prevalence of HCH remains poorly defined. In addition, the reported birth prevalence of ACH in Europe and globally may not be applicable to France, given its relatively high rate of pregnancy terminations for medical reasons. This retrospective study provides the first birth prevalence estimates for ACH and HCH in France, using the French National Registry of Rare Diseases (Banque Nationale de Données Maladies Rares, BNDMR).

As of January 2024, 766 patients with ACH (ORPHA:15) and 408 with HCH (ORPHA:429) were identified. Most patients were diagnosed and cared for within the network of constitutional bone diseases centers (ACH: 71.3%; HCH: 63.4%). Overall, 85.5% of ACH cases and 57.2% of HCH cases were related to de novo genetic variants (p < 0.0001). ACH was diagnosed prenatally in 40.8% and at birth in 40.6% of patients, whereas HCH was diagnosed postnatally in 65.7% of cases (p < 0.0001). To estimate live birth prevalence, we focused on pediatric patients (0-15 years) born between 2008 and 2023. The mean (range) live birth prevalence was 3.27 per 100,000 for ACH (1.90-4.03) and 1.31 per 100,000 for HCH (0.54-2.08).

This study provides the first nationwide birth prevalence estimates for ACH and HCH in France, leveraging data from BNDMR. ACH is often identified prenatally, whereas HCH is predominantly diagnosed postnatally. The prevalence of HCH may be underestimated due to under-recognition of milder forms. With the emergence of specific therapies for ACH, and for HCH in the near future, strengthening specialized care pathways is critical to ensure equitable access to timely diagnosis and interventions.

Not applicable.