A new osteochondrodysplasia with severe osteopenia, preaxial polydactyly, clefting and dysmorphic features resembling filamin-related disorders.

Background: We report a 19-week gestation female foetus with a new syndrome characterised by increased nuchal translucency and severe micromelia with campomelia evident from the early second trimester.

Methods And Results: Cytogenetic studies performed on amniocytes revealed a normal female karyotype. Autopsy after termination of pregnancy showed facial dysmorphism, cleft palate, bowed, shortened limbs, hypoplasia of the preaxial elements in all four limbs with accompanying accessory ossification centres in the feet, and severe calvarial underossification. A diagnosis of otopalatodigital syndrome type 2, associated with mutations in FLNA, a gene encoding the cytoskeletal protein filamin A, was considered but discarded due to the severity of micromelia, early lethality, and the presence of generalised osteopenia instead of hyperostosis. The degree of undermodelling and campomelia was reminiscent of another group of conditions that include atelosteogenesis types 1 and 3, caused by mutations in FLNB. Sequencing analysis did not reveal any pathogenic mutation in the three paralogous filamin genes: FLNA, FLNB and FLNC.

Conclusion: Clinical, radiological and cytogenetic findings suggest that this phenotype is a new entity whose aetiopathogenesis may be functionally related to the filaminopathies.