Thanatophoric Dysplasia Type 1 Treated with Vosoritide: A Case Report

Thanatophoric dysplasia type 1 (TD1) is the most severe form of FGFR3-related skeletal dysplasia, with high perinatal mortality and no approved pharmacologic therapies. Vosoritide, a C-type natriuretic peptide analogue that counteracts FGFR3 overactivation, improves growth in achondroplasia, but its effects in TD1 remain unexplored.

We report the response to vosoritide therapy in a 9-year-old girl with genetically confirmed TD1 (c.2420G>T). Vosoritide was initiated at a dose of 15 µg/kg/day subcutaneously and increased to 30 µg/kg/day after 16 months. Growth velocity, anthropometry, pulmonary function, densitometry, and safety were assessed longitudinally over 28 months. At baseline, height was 78.6 cm (-10.9 SDS) and annual growth velocity (AGV) 1.6 cm/year (-4.7 SDS). After 28 months, height increased by +1.3 SDS and AGV by +2.0 cm/year (+3 SDS from baseline). Lung vital capacity improved by 65%. Serial MRI demonstrated persistent severe foramen magnum stenosis without radiological progression. Adverse events were limited to transient injection-site reactions and mild vasovagal episodes; no major safety concerns emerged.

Vosoritide was well tolerated and improved growth velocity and lung function in this long-term TD1 survivor, suggesting therapeutic potential even in severe FGFR3 overactivation. Given TD1's rarity, larger studies and further off-label experience are essential to validate these findings.