Frontometaphyseal dysplasia is a disorder involving abnormalities in skeletal development and other health problems. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, otopalatodigital syndrome type 2, Melnick-Needles syndrome, and terminal osseous dysplasia. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and bony abnormalities involving various areas of the skeleton.

Variants (also called mutations) in the FLNA gene cause frontometaphyseal dysplasia type 1. Variants in the MAP3K7 gene cause frontometaphyseal dysplasia type 2, and TAB2 gene variants cause type 3.

Frontometaphyseal dysplasia is a rare disorder; over a hundred cases have been reported worldwide.

When frontometaphyseal dysplasia is caused by variants in the FLNA gene, it is inherited in an X-linked dominant pattern. The FLNA gene  is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a variant in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a variant in the only copy of the gene in each cell causes the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Males with frontometaphyseal dysplasia type 1 generally have more severe signs and symptoms of the disorder than do females, who may show only the characteristic facial features.

Published Date: June 16, 2022
Published By: National Institutes of Health