Information on the following diseases can be found in the Related Disorders section of this report:

• oculo-auricular-vertebral spectrum
• Duane-radial ray syndrome
• branchiootorenal syndrome
• VACTERL association

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.

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.

The prevalence of Townes-Brock syndrome is not known but has been estimated to be at least 1 in 250,000 births. This condition affects males and females in equal numbers.

Symptoms of the following disorders can be similar to those of Townes-Brocks syndrome. Comparisons may be useful for a differential diagnosis:

The oculo-auricular-vertebral spectrum (OAVS) disorders are associate with malformations of the eyes, ears and spine. Oculo-auriculo-vertebral disorder (OAVD) represents the mildest form of the disorder, while Goldenhar syndrome is the most severe form. Hemifacial microstomia appears to be an intermediate form. The disorder is characterized by a wide spectrum of symptoms and physical features that may vary greatly in range and severity from case to case. However, such abnormalities tend to involve the cheekbones, jaw, mouth, ears, eyes, and/or bones of the spinal column (vertebrae). (For more information about this disorder, choose “oculo-auricular-vertebral spectrum” as your search term in the Rare Disease Database.)

Duane-radial ray syndrome is a disorder that affects the eyes and causes abnormalities of bones in the arms and hands. Bone abnormalities in the hands include malformed or absent thumbs, an extra thumb, or a thumb that looks like a finger. Partial or complete absence of bones in the forearm is also common. Together, these hand and arm abnormalities are called radial ray malformations. The Duane anomaly is an eye movement disorder in which the affected individual has a limited ability to move the eye inward toward the nose (adduction), outward toward the ear (abduction), or in both directions. In addition, when the affected eye(s) moves inward toward the nose, the eyeball retracts (pulls in) to the socket.

Branchiootorenal syndrome (BOR) syndrome is a rare disorder inherited as an autosomal dominant genetic trait. This disorder is characterized by pits or ear tags in front of the outer ear, abnormal passages from the throat to the outside surface of the neck (branchial fistulas), branchial cysts, hearing loss and/or kidney (renal) abnormalities. (For more information about this disorder, choose “branchio-oto-renal” as your search term in the Rare Disease Database.)

VACTERL association is a nonrandom association of birth defects that affects multiple organ systems. The term VACTERL is an acronym with each letter representing the first letter of one of the more common findings seen in affected children: (V) = vertebral abnormalities, (A) = anal atresia, (C) = cardiac (heart) defects, (T) = tracheoesophageal fistula, (E) =esophageal atresia, (R) = renal (kidney) abnormalities and (L) = limb abnormalities. (For more information about this disorder, choose “VACTERL” as your search term in the Rare Disease Database.)

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.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Kohlhase, J. (Posted 1/24/07). Townes-Brocks Syndrome. In Genereviews at Genetests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2007. Available at http://www.genetests.org accessed 3/07.

Lachiewicz AM, Hodge C. Townes-Brocks Syndrome. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:262.

Botzenhart EM, Bartalini G, Blair E, et al. Townes-Brocks syndrome: twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region. Hum Mutat 2007:28:204-5.

Botzenhart EM, Green A, Ilyina H, et al. SALL1 mutation analysis in Townes-Brocks syndrome: twelve novel mutations and expansion of the phenotype. Hum Mutat 2005:26-282.

Devriendt K, Fryns JP, Lemmens F, et al. Somatic mosaicism and variable expression of Townes-Brocks syndrome. Am J Med Genet 2002: 111-230-1.

Kohlhase J. SALL1 mutations in Townes-Brocks syndrome and related disorders. Hum Mutat 2000: 16:460-6.

Townes PL and Brocks ER. Hereditary syndrome of imperforate anus with hand, foot and ear anomalies. J Pediatr 1972:81;321-326.