Thanatophoric Dysplasia Type 1 Treated with Vosoritide: A Case Report

BACKGROUND: 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 remains unexplored.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.