Otopalatodigital types 1 and 2, syndrome ... (otopalatodigital syndrome types 1 and 2) - Gen FLNA.
Otopalatodigital syndrome type 1 is a disorder characterized by abnormalities in skeletal development. This process is part of a group of related disorders calls otopalatodigital disorders spectrum, including otopalatodigital syndrome type 1, type 2 syndrome otopalatodigital, frontometaphyseal dysplasia syndrome Melnick-Needles.
The otopalatodigital syndrome type 1 is usually the slightest disturbance otopalatodigital spectrum. Generally, people with this disorder have characteristic facial features, including widely spaced eyes and tilt downward, prominent brow ridges, a small, flat nose, hearing loss, chest deformities, abnormalities of the fingers and feet, fingertips square, shortened thumb and second finger unusually long feet. Affected people may be born with cleft palate. Some affected individuals have slightly inclined limbs and limited range of motion in certain joints. Males with this disorder often have more intense than women, which can display only the facial features characteristic signs and symptoms.
The otopalatodigital syndrome type 2 involves abnormalities , skeletal development and other health problems. In addition to the signs and symptoms of type 1, type 2 disease can cause problems in other areas of the body such as the brain and heart. Additional features include camptodactilia, shortened or absent thumbs, irregular underdeveloped ribs which may cause breathing problems and other abnormal or absent bones. Addition of skeletal abnormalities, people with type 2 otopalatodigital syndrome may have developmental delay, hydrocephalus, protrusion of the abdominal organs through the navel, heart defects, abnormalities in chest, obstruction of the ureters and, in males , urethral opening in the underside of the penis. Males with this disorder usually do not live beyond their first year because their underdeveloped ribcage does not allow enough breathing lung expansion.
This process is due to mutations in the gene FLNA, located on the long arm of chromosome X (Xq28). This gene encodes the protein filamin A, which helps to build the cell cytoskeleton. Filamin A binds to another protein called actin, helping to form the branched network of filaments forming the cell cytoskeleton. Filamin A also binds to actin to perform various functions within the cell, including regulation of skeletal development and brain, blood vessel formation and blood clotting.
They have identified a small number of mutations in exons 3, 4, and 5 of FLNA gene in individuals with otopalatodigital syndrome. Mutations in the gene cause changes in filamin. Mutations responsible otopalatodigital syndrome are described as "gain of function" that appear to increase the activity of the protein filamin or cause a new atypical protein function.
Otopalatodigital syndrome is inherited as a dominant X - linked pattern as the gene related to this alteration is on chromosome X. In women, a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males, a mutation in the single copy of the gene in each cell causes the disorder. In most cases, men have more severe symptoms of the disease than women. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome.
Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome otopalatodigital, by complete PCR amplification of the exons of the gene FLNA, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).