Townes-Brocks syndrome is a genetic condition that affects several parts of the body. The most common features of this condition are a malformation of the anal opening (imperforate anus), abnormally shaped ears, and hand malformations that most often affect the thumbs. People with this condition often have at least two of these three major features.

Other signs and symptoms of Townes-Brocks syndrome can include kidney abnormalities, mild to profound hearing loss, eye abnormalities, heart defects, foot abnormalities, and genital malformations. These features vary among affected individuals, even within the same family. Mild intellectual disability or learning problems have been reported in about 10 percent of people with Townes-Brocks syndrome.

Signs & Symptoms

The absence of the anal opening (imperforate anus) is the most common feature of TBS. Small ears and a folded rim of skin and cartilage around the outer ear are usually present. Congenital sensorineural and/or conductive hearing loss can range from mild to severe and can be progressive. The most common thumb malformations are three bones instead of two (triphalangeal thumbs) and duplicated thumbs (preaxial polydactyly). Feet anomalies occur less frequently and include a short third toe, overlapping toes and flat feet. Kidney dysfunction can occur with or without kidney malformations. Typical kidney anomalies include displaced or rotated kidneys, horseshoe kidney, polycystic kidneys, and underdeveloped kidneys. Abnormalities of the heart, eye and spine are infrequently associated with Townes-Brocks syndrome. Mental retardation occurs in approximately 10% of affected individuals.

Causes

Townes-Brocks syndrome is an autosomal dominant genetic disorder. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The SALL1 gene is the only gene known to be associated with Townes-Brocks syndrome. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. Approximately 50% of affected individuals have the condition as a result of a new mutation. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Diagnosis

The diagnosis of Townes-Brocks syndrome is based on clinical symptoms. Molecular genetic testing for mutations in the SALL1 gene is available to confirm the diagnosis.

Treatment

Treatment of Townes-Brocks syndrome often requires surgery for malformations associated with this condition. Hearing evaluation should be conducted if TBS is suspected. Ultrasound and laboratory tests should be performed to monitor kidney function. A baseline echocardiogram should be performed by a cardiologist.

• Genetic counseling is recommended for affected individuals and their families.
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