Thanatophoric dysplasia: prevalence, clinical characteristics, and molecular findings in a public hospital from Western Mexico.

BACKGROUND

Thanatophoric dysplasia (TD) is a lethal FGFR3 chondrodysplasia characterized by micromelia and bowed femurs (TD1), or straight femurs and cloverleaf skull (TD2).

OBJECTIVE

To determine the prevalence and clinical and molecular characteristics of patients with TD in a public hospital in Western Mexico.

MATERIALS AND

METHODS

Observational, retrospective and descriptive study. Ten live births with TD were included from a total of 118,154 births between 2009 and 2024 at the Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Mexico). The FGFR3 gene was analyzed by PCR, followed by direct sequencing of exons 4-6 and 8.

RESULTS

The prevalence of TD was 0.85 per 10,000 births (95% CI: 0.32-1.37). All presented TD1 (4 men and 6 women), sporadic occurrence and 4/10 advanced paternal age. Phenotype: short stature, macrocephaly, hypotonia, distinctive facial features, narrow thorax, prominent abdomen, micromelia, redundant skinfolds, trident hand, short ribs, rhizomelic shortening, irregular metaphyses, platyspondyly and bowed femurs. In seven, pathogenic variants in FGFR3 were identified: p.Arg248Cys (n = 3), p.Ser371Cys (n = 2), p.Gly370Cys (n = 1) and p.Try373Cys (n = 1).

CONCLUSIONS

One in 11,815 infants was born with T1D. Molecular analysis allows to distinguish it from other lethal chondrodysplasias and to provide appropriate genetic counseling.