FLNA Gene

Otopalatodigital syndrome type 1 is a disorder primarily involving abnormalities in skeletal development. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 2, frontometaphyseal dysplasia, 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 skeletal abnormalities involving the fingers or toes (digits).

Otopalatodigital syndrome type 1 is usually the mildest of the otopalatodigital spectrum disorders. People with this condition usually have characteristic facial features including wide-set and downward-slanting eyes; prominent brow ridges; and a broad, flat nose. Affected individuals have abnormalities of the fingers and toes, such as blunt, square-shaped (spatulate) fingertips; shortened thumbs and big toes; unusually long second toes; and a wide gap between the first and second toes (known as a sandal gap). Affected individuals also have hearing loss.

Infants with otopalatodigital syndrome type 1 may be born with an opening in the roof of the mouth (a cleft palate). Individuals with this condition often have fewer teeth than normal (hypodontia). They may have mild abnormal curvature (bowing) of their limbs, and limited range of motion in some joints. People with otopalatodigital syndrome type 1 may be somewhat shorter than other members of their family.

Females with otopalatodigital syndrome type 1 often have more variable signs and symptoms compared to affected males, with females typically having fewer signs and symptoms.

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 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.

Terminal osseous dysplasia is a disorder primarily involving skeletal abnormalities and certain skin changes. 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, frontometaphyseal dysplasia, and Melnick-Needles syndrome. In general, these disorders involve hearing loss caused by malformations in tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers or toes (digits), although not every condition in the spectrum has all of these features.

Terminal osseous dysplasia occurs only in females; males with the condition do not survive to birth. The skeletal abnormalities in people with this condition typically include permanently bent fingers and toes (camptodactyly) and underdevelopment (hypoplasia), shortening, or fusion of the bones in the wrists and hands. The outer layer of bone (cortex) in other parts of the skeleton may be abnormal, and some affected individuals have bowed arms or legs or are shorter than their peers.

Skin abnormalities are also common in terminal osseous dysplasia. Many individuals with the condition have dark patches of skin on their face, often near the temples. In addition, affected infants commonly develop noncancerous (benign) tumors called fibromas on their fingers or toes. The tumors may reappear after being removed, but they tend to go away and stop reoccurring in childhood.

Other signs and symptoms can occur in people with terminal osseous dysplasia, including extra oral frenulae, which are the thin pieces of tissue in the mouth that connect the inside of the lips to the gums; widely spaced eyes; and hair loss. Some people with this condition have an abnormality in the muscular wall (septum) that separates the right and left sides of the heart (cardiac septal defect).

Intestinal pseudo-obstruction is a condition characterized by impairment of the muscle contractions that move food through the digestive tract. It can occur at any time of life, and its symptoms range from mild to severe. The condition may arise from abnormalities of the gastrointestinal muscles themselves (myogenic) or from problems with the nerves that control the muscle contractions (neurogenic).

Intestinal pseudo-obstruction leads to a buildup of partially digested food in the intestines. This buildup can cause abdominal swelling (distention) and pain, nausea, vomiting, and constipation or diarrhea. Affected individuals experience loss of appetite and impaired ability to absorb nutrients, which may lead to malnutrition. These symptoms resemble those of an intestinal blockage (obstruction), but in intestinal pseudo-obstruction no blockage is found.

Depending on the cause of intestinal pseudo-obstruction, affected individuals can have additional signs and symptoms. Some people with intestinal pseudo-obstruction have bladder dysfunction such as an inability to pass urine. Other features may include decreased muscle tone (hypotonia) or stiffness (spasticity) of the torso and limbs, weakness in the muscles that control eye movement (ophthalmoplegia), intellectual disability, seizures, unusual facial features, or recurrent infections.

When intestinal pseudo-obstruction occurs by itself, it is called primary or idiopathic intestinal pseudo-obstruction. The disorder can also develop as a complication of another health problem; in these cases, it is called secondary intestinal pseudo-obstruction. The condition can be episodic (acute) or persistent (chronic).

Otopalatodigital syndrome type 2 is a disorder primarily involving abnormalities in skeletal development. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, frontometaphyseal dysplasia, 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 skeletal abnormalities involving the fingers 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). Affected individuals often have abnormalities of the fingers and toes, such as unusual curvature of the fingers (camptodactyly) and shortened or absent thumbs and big toes. People with otopalatodigital syndrome type 2 usually have short stature, abnormally curved (bowed) bones in the arms and legs, and other abnormal or absent bones. Underdeveloped ribs can cause problems with breathing in affected individuals. Some people with this condition have an opening in the roof of the mouth (a cleft palate) or hearing loss.

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 compared to affected females. Males with this condition typically do not survive past infancy because of respiratory failure due to an underdeveloped rib cage.

FG syndrome is a genetic condition that affects many parts of the body and occurs almost exclusively in males. "FG" represents the surname initials of the first family diagnosed with the disorder.

FG syndrome affects intelligence and behavior. Almost everyone with the condition has intellectual disability, which ranges from mild to severe. Affected individuals tend to be friendly, inquisitive, and hyperactive, with a short attention span. Compared to people with other forms of intellectual disability, their socialization and daily living skills are strong, while verbal communication and language skills tend to be weaker.

The physical features of FG syndrome include weak muscle tone (hypotonia), broad thumbs, and wide first (big) toes. Abnormalities of the tissue connecting the left and right halves of the brain (the corpus callosum) are also common. Most affected individuals have constipation, and many have abnormalities of the anus such as an obstruction of the anal opening (imperforate anus). People with FG syndrome also tend to have a distinctive facial appearance including small, underdeveloped ears; a tall, prominent forehead; and outside corners of the eyes that point downward (down-slanting palpebral fissures).

Additional features seen in some people with FG syndrome include widely set eyes (hypertelorism), an upswept frontal hairline, and a large head compared to body size (relative macrocephaly). Other health problems have also been reported, including heart defects, seizures, undescended testes (cryptorchidism) in males, and a soft out-pouching in the lower abdomen (an inguinal hernia).

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

Melnick-Needles syndrome is usually the most severe of the otopalatodigital spectrum disorders. People with this condition are usually of short stature, have an abnormal curvature of the spine (scoliosis), partial dislocation (subluxation) of certain joints, and unusually long fingers and toes. They may have bowed limbs; underdeveloped, irregular ribs that can cause problems with breathing; and other abnormal or absent bones.

Characteristic facial features may include bulging eyes with prominent brow ridges, excess hair growth on the forehead, round cheeks, a very small lower jaw and chin (micrognathia), and misaligned teeth. One side of the face may appear noticeably different from the other (facial asymmetry). Some individuals with this disorder have hearing loss.

In addition to skeletal abnormalities, individuals with Melnick-Needles syndrome may have obstruction of the ducts between the kidneys and bladder (ureters) or heart defects.

Males with Melnick-Needles syndrome generally have much more severe signs and symptoms than do females, and in almost all cases die before or soon after birth.