Frontometaphyseal dysplasia

Alternate names

FMD

Definition

Frontometaphyseal dysplasia (FMD) is a genetic disorder characterized by abnormalities in skeletal development and problems in other organs of the body.

Summary

It is part of a group of diseases called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, otopalatodigital syndrome type 2, and Melnick-Needles syndrome.

Epidemiology

Frontometaphyseal dysplasia is a rare disorder; only a few dozen cases have been reported worldwide.

Cause

• Mutations in the FLNA gene cause frontometaphyseal dysplasia.
• The FLNA gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move.
• Filamin A binds to another protein called actin, and helps the actin to form the branching network of filaments that make up the cytoskeleton.
• Filamin A also links actin to many other proteins to perform various functions within the cell.

Gene mutations

• A small number of mutations in the FLNA gene have been identified in people with frontometaphyseal dysplasia.
• These mutations are described as "gain-of-function" because they appear to enhance the activity of the filamin A protein or give the protein a new, atypical function.
• Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of frontometaphyseal dysplasia.

Inheritance

X-linked dominant inheritance

• This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes.
• In females (who have two X chromosomes), a mutation 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 mutation in the only copy of the gene in each cell causes the disorder.
• In most cases, males experience more severe symptoms of the disorder than females.
• A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Signs and symptoms

In general, males tend to be more severely affected than females. Females may present with the characteristic craniofacial features and scoliosis.

The main symptoms in males include:

• Skeletal dysplasia (enlargement of the bones in the frontal part of the skull, skull base sclerosis, as well as in the medial part (diaphysis) of the long bones and the part between the diaphysis and the end parts of the bones, small tips of the bones of the fingers)
• Progressive contractures of the hand and other bones of the body over the first 20 years resulting in limited movement of the hand, fingers, wrists, elbows, knees, and ankles
• Scoliosis
• Limb bowing
• Deformed fingers
• Facial dysmorphism (big frontal, wide-spaced eyes, down-slanting eye slits, broad nose bridge and tip, small or less teeth than normal and occasionally craniosynostosis (when the sutures of the skull closed too early))
• Hearing loss.
• Other features include congenital heart malformation, congenital subglottic stenosis (narrowing of the airways), a slender body, with underdeveloped muscles around the shoulders and in the inside of the hands.
• Males with frontometaphyseal dysplasia can present with obstruction of the ducts connecting the ureters with bladder and enlarged kidneys (hydronephrosis).
• Intelligence is normal.

Diagnosis

• The diagnosis of an X-OPD spectrum disorder is established in a male proband with characteristic clinical and radiographic features and a family history consistent with X-linked inheritance.
• Identification of a hemizygous pathogenic variant in FLNA by molecular genetic testing can confirm the diagnosis if clinical features, radiographic features, and/or family history are inconclusive.[1].

Treatment

Treatment depends on the symptoms present in the person, and may include:

• Hearing loss aids for deafness
• Surgery to correct the facial deformities including the frontal deformity
• Surgery to correct the joint contractures, the limb bowing, and the scoliosis.

NIH genetic and rare disease info

• NIH info on Frontometaphyseal dysplasia

Frontometaphyseal dysplasia is a rare disease.

• Need help finding a doctor or specialist anywhere in the world? WikiMD's DocFinder can help with millions of doctors!

This article is a stub. Help WikiMD grow by registering to expand it. Editing is available only to registered and verified users. About WikiMD: A comprehensive, free health & wellness encyclopedia.