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Otopalatodigital syndrome type 2 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, frontometaphyseal dysplasia, 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). Otopalatodigital syndrome type 2 also tends to cause problems in other areas of the body, such as the brain and heart.
People with otopalatodigital syndrome type 2 have characteristic facial features including wide-set and downward-slanting eyes; prominent brow ridges; a broad, flat nose; and a very small lower jaw and chin (micrognathia). The base of the skull may be thickened. Some people with this disorder have hearing loss. Affected individuals are usually of short stature and may have abnormalities of the fingers and toes, such as unusual curvature of the fingers (camptodactyly) and shortened or absent thumbs and big toes. They may have bowed limbs; underdeveloped, irregular ribs that may cause problems with breathing; and other abnormal or absent bones. Some may be born with an opening in the roof of the mouth (a cleft palate).
In addition to skeletal abnormalities, individuals with otopalatodigital syndrome type 2 may have developmental delay, increased fluid in the center of the brain (hydrocephalus), protrusion of the abdominal organs through the navel (omphalocele), heart defects, chest abnormalities, obstruction of the ducts between the kidneys and bladder (ureters), and, in males, opening of the urethra on the underside of the penis (hypospadias).
Males with otopalatodigital syndrome type 2 generally have much more severe signs and symptoms than do females. Males with the disorder usually do not live beyond their first year, because their underdeveloped rib cage does not allow sufficient lung expansion for breathing.
Otopalatodigital syndrome type 2 is a rare disorder, affecting fewer than 1 in every 100,000 individuals. Its specific incidence is unknown.
Mutations in the FLNA gene cause otopalatodigital syndrome type 2.
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 otopalatodigital syndrome type 2. The mutations all result in changes to the filamin A protein in the region that binds to actin. The mutations responsible for otopalatodigital syndrome type 2 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 otopalatodigital syndrome type 2.
Changes in this gene are associated with otopalatodigital syndrome type 2.
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.
These resources address the diagnosis or management of otopalatodigital syndrome type 2 and may include treatment providers.
You might also find information on the diagnosis or management of otopalatodigital syndrome type 2 in Educational resources and 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.
You may find the following resources about otopalatodigital syndrome type 2 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.
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (https://rarediseases.info.nih.gov/gard).
actin ; atypical ; camptodactyly ; cell ; chromosome ; cleft palate ; cytoskeleton ; developmental delay ; dysplasia ; gene ; hydrocephalus ; hypospadias ; incidence ; inheritance ; inherited ; lower jaw ; micrognathia ; mutation ; obstruction ; omphalocele ; palate ; protein ; sex chromosomes ; short stature ; spectrum ; stature ; syndrome ; X-linked dominant
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
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