Otopalatodigital syndrome spectrum disorders: otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick-Needles syndrome.

The term otopalatodigital syndrome spectrum disorders is an umbrella category that includes four phenotypically related conditions, otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick - Needles syndrome. The phenotype of these conditions in the male ranges from a severe perinatally lethal multiple malformation syndrome to a mild skeletal dysplasia. Most, but not all, instances of these conditions are associated by mutations in the X-linked gene encoding the cytoskeletal protein filamin A. Mutations in this gene are clustered, exhibit a strong genotype-phenotype correlation and are presumed to exert their effect by a gain-of-function mechanism.