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Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Frontometaphyseal dysplasia

Reviewed November 2007

What is frontometaphyseal dysplasia?

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, and Melnick-Needles syndrome. 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 skeletal abnormalities involving the fingers and/or toes (digits).

Frontometaphyseal dysplasia is distinguished from the other otopalatodigital spectrum disorders by the presence of joint deformities called contractures that restrict the movement of certain joints. People with frontometaphyseal dysplasia may also have bowed limbs, an abnormal curvature of the spine (scoliosis), and abnormalities of the fingers and hands.

Characteristic facial features may include prominent brow ridges; wide-set and downward-slanting eyes; a very small lower jaw and chin (micrognathia); and small, missing or misaligned teeth. Some affected individuals have hearing loss.

In addition to skeletal abnormalities, individuals with frontometaphyseal dysplasia may have obstruction of the ducts between the kidneys and bladder (ureters), heart defects, or constrictions in the passages leading from the windpipe to the lungs (the bronchi) that can cause problems with breathing.

Males with frontometaphyseal dysplasia generally have more severe signs and symptoms of the disorder than do females, who may show only the characteristic facial features.

How common is frontometaphyseal dysplasia?

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

What genes are related to frontometaphyseal dysplasia?

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.

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.

Related Gene(s)

Changes in this gene are associated with frontometaphyseal dysplasia.

  • FLNA

How do people inherit frontometaphyseal dysplasia?

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.

Where can I find information about diagnosis or management of frontometaphyseal dysplasia?

These resources address the diagnosis or management of frontometaphyseal dysplasia and may include treatment providers.

  • Gene Review: Otopalatodigital Spectrum Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1393)
  • Genetic Testing Registry: Frontometaphyseal dysplasia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265293)

You might also find information on the diagnosis or management of frontometaphyseal dysplasia in Educational resources (http://www.ghr.nlm.nih.gov/condition/frontometaphyseal-dysplasia/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/frontometaphyseal-dysplasia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about frontometaphyseal dysplasia?

You may find the following resources about frontometaphyseal dysplasia helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What if I still have specific questions about frontometaphyseal dysplasia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding frontometaphyseal dysplasia?

actin ; atypical ; bronchi ; cell ; chromosome ; cytoskeleton ; dysplasia ; gene ; inheritance ; inherited ; joint ; lower jaw ; micrognathia ; mutation ; obstruction ; palate ; protein ; scoliosis ; sex chromosomes ; spectrum ; syndrome ; X-linked dominant

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • OMIM: FRONTOMETAPHYSEAL DYSPLASIA (http://omim.org/entry/305620)
  • Gene Review: Otopalatodigital Spectrum Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1393)
  • Giuliano F, Collignon P, Paquis-Flucklinger V, Bardot J, Philip N. A new three-generational family with frontometaphyseal dysplasia, male-to-female transmission, and a previously reported FLNA mutation. Am J Med Genet A. 2005 Jan 15;132A(2):222. (http://www.ncbi.nlm.nih.gov/pubmed/15523633?dopt=Abstract)
  • Morava E, Illés T, Weisenbach J, Kárteszi J, Kosztolányi G. Clinical and genetic heterogeneity in frontometaphyseal dysplasia: severe progressive scoliosis in two families. Am J Med Genet A. 2003 Jan 30;116A(3):272-7. (http://www.ncbi.nlm.nih.gov/pubmed/12503106?dopt=Abstract)
  • Robertson SP, Jenkins ZA, Morgan T, Adès L, Aftimos S, Boute O, Fiskerstrand T, Garcia-Miñaur S, Grix A, Green A, Der Kaloustian V, Lewkonia R, McInnes B, van Haelst MM, Mancini G, Illés T, Mortier G, Newbury-Ecob R, Nicholson L, Scott CI, Ochman K, Brozek I, Shears DJ, Superti-Furga A, Suri M, Whiteford M, Wilkie AO, Krakow D. Frontometaphyseal dysplasia: mutations in FLNA and phenotypic diversity. Am J Med Genet A. 2006 Aug 15;140(16):1726-36. Erratum in: Am J Med Genet A. 2006 Dec 15;140(24):2840. Macini, Grazia [corrected to Mancini, Grazia]. (http://www.ncbi.nlm.nih.gov/pubmed/16835913?dopt=Abstract)
  • Robertson SP, Twigg SR, Sutherland-Smith AJ, Biancalana V, Gorlin RJ, Horn D, Kenwrick SJ, Kim CA, Morava E, Newbury-Ecob R, Orstavik KH, Quarrell OW, Schwartz CE, Shears DJ, Suri M, Kendrick-Jones J, Wilkie AO; OPD-spectrum Disorders Clinical Collaborative Group. Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans. Nat Genet. 2003 Apr;33(4):487-91. Epub 2003 Mar 3. (http://www.ncbi.nlm.nih.gov/pubmed/12612583?dopt=Abstract)
  • Robertson SP. Otopalatodigital syndrome spectrum disorders: otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick-Needles syndrome. Eur J Hum Genet. 2007 Jan;15(1):3-9. Epub 2006 Aug 23. (http://www.ncbi.nlm.nih.gov/pubmed/16926860?dopt=Abstract)
  • Zenker M, Nährlich L, Sticht H, Reis A, Horn D. Genotype-epigenotype-phenotype correlations in females with frontometaphyseal dysplasia. Am J Med Genet A. 2006 May 15;140(10):1069-73. (http://www.ncbi.nlm.nih.gov/pubmed/16596676?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2007
Published: December 22, 2014