Oto-palato-digital syndrome type 1

Other Names: Otopalatodigital syndrome type 1; Taybi syndrome; OPD syndrome; OPD syndrome 1; OPD1 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.

Epidemiology

Otopalatodigital syndrome type 1 is a rare disorder, affecting fewer than 1 in every 100,000 individuals. Its specific incidence is unknown.

Cause

Otopalatodigital syndrome type 1 is caused by mutations in the FLNA gene. 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 attaches (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.

The FLNA gene mutations that cause otopalatodigital syndrome type 1 result in changes to the filamin A protein in the region that binds to actin. The mutations are described as "gain-of-function" because they appear to lead to a protein with an increased ability to bind to actin. Researchers believe that the mutations impair the stability of the cytoskeleton and disrupt cellular 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 1.

Inheritance

This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males, who have only one X chromosome, a mutation in the only copy of the gene in each cell is sufficient to cause the condition. In females, who have two copies of the X chromosome, one altered copy of the gene in each cell can lead to less severe features of the condition or may cause no signs or symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Signs and symptoms

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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Anodontia(Failure of development of all teeth)
• Cleft palate(Cleft roof of mouth)
• Depressed nasal bridge(Depressed bridge of nose)
• Downslanted palpebral fissures(Downward slanting of the opening between the eyelids)
• Hearing impairment(Deafness)
• Hypertelorism(Wide-set eyes)
• Intellectual disability, mild(Mental retardation, borderline-mild)
• Limitation of joint mobility(Decreased joint mobility)
• Oligodontia(Failure of development of more than six teeth)
• Prominent supraorbital ridges(Prominent brow)
• Sandal gap(Gap between 1st and 2nd toes)
• Short hallux(Short big toe)
• Skeletal dysplasia
• Wide nasal bridge(Broad nasal bridge)

30%-79% of people have these symptoms

• Abnormality of the metacarpal bones(Abnormality of the long bone of hand)
• Bowing of the long bones(Bowed long bones)
• Elbow dislocation(Dislocations of the elbows)
• Hypoplastic frontal sinuses
• Increased bone mineral density(Increased bone density)
• Proximal placement of thumb(Attachment of thumb close to wrist)
• Short distal phalanx of finger(Short outermost finger bone)
• Short palm
• Short thumb(Short thumbs)
• Thickened calvaria(Increased thickness of skull cap)

5%-29% of people have these symptoms

• Abnormal vertebral segmentation and fusion
• Abnormality of the tarsal bones(Abnormal ankle bones)
• Synostosis of carpal bones(Fusion of wrist bones)

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.

Treatment

Surgical treatment may be required for hand and foot malformations. Monitoring and surgical intervention as needed for scoliosis; physiotherapy for contractures; cosmetic surgery may correct the fronto-orbital deformity; continuous positive airway pressure (CPAP) and mandibular distraction can improve airway complications related to micrognathia; hearing aids for deafness; evaluation with anesthesiology if intubation and ventilation are required due to laryngeal stenosis.

NIH genetic and rare disease info

• NIH info on Oto-palato-digital syndrome type 1

Oto-palato-digital syndrome type 1 is a rare disease.

Oto-palato-digital syndrome type 1 Resources
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