Townes-Brocks syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at December 2, 2016
StartDiseasesTownes-Brocks syndrome

Townes-Brocks syndrome or TBS is a rare genetic disorder characterized by an abnormal anal opening, abnormal ear development that causes hearing impairment, and thumb malformation. Townes-Brocks syndrome affects females and males equally with a prevalence estimated at 1 in 250,000 births, although it may be under-diagnosed. Less than 200 cases of Townes-Brocks syndrome have been diagnosed in the world. 

Contents

Definition & Facts

Townes-Brocks syndrome is an autosomal dominant genetic disorder with several defining characteristics. People with this congenital disorder have an imperforate anus, or a lack of an anal opening, in addition to other developmental abnormalities.

Additional health complications and signs may also occur, such as kidney dysfunction. The abnormalities of TBS are present prenatally and may range from minor to severe. The condition was first described in 1972 by Dr. Philip Townes, a geneticist, and Dr. Eric Brocks. 

Symptoms & Complaints

TBS affects many areas of the body. The obstruction of the anal opening is the most common feature of Townes-Brocks syndrome along with abnormal ear development and hand malformations that typically affect the thumb.

The most common thumb malformations associated with the disorder are duplicated thumbs (preaxial polydactyly) or three bones in the thumb instead of two (triphalangeal thumb). Most people with Townes-Brocks syndrome have at least two of these three primary features in addition to other symptoms.

Less common than hand deformities are feet abnormalities such as a third short toe, flat feet, or overlapping toes. Other hand and foot deformities that may occur include hypoplastic thumbs, webbed toes or fingers, and fused wrist bones.

TBS may also cause more broad symptoms. Ear deformities can lead to mild to total hearing loss. Conductive and/or sensorineural hearing loss can be progressive. About 10% of people with TBS have some level of intellectual disability or learning disability.

Many people with Townes-Brocks syndrome have some level of kidney dysfunction with or without kidney malformations such as displaced kidneys, horseshoe kidney, or underdeveloped kidneys. Deformities of the heart, eye, spine, and genitals are less frequently associated with TBS.

Hypothyroidism, or an underactive thyroid that fails to produce enough hormones, has also been associated with the disorder. The symptoms of TBS are highly variable, even within a family. While the classic symptoms of the disorder, including the hand, ear, and anal malformations, are present at birth, other symptoms can develop at any age. 

Causes

Townes-Brocks syndrome is an autosomal dominant genetic disorder that can occur when a single copy of a mutated SALL1 gene is passed on to a child. It can also result from a new genetic mutation.

As an autosomal dominant disease, a child only needs to get the mutated gene from one parent to get the disease. In many cases, a parent is also affected by Townes-Brocks syndrome, although the symptoms may be very different from parent to child. A genetic carrier of TBS has a 50 percent chance of passing on the abnormal gene to a child, whether the resulting child is a male or female.

It is still unknown how the gene mutation produces the symptoms of Townes-Brocks syndrome. Townes-Brocks syndrome is the primary result of defects in the SALL1 gene on chromosome 16, but defects can also cause bronciootorenal syndrome (BOR), which must be ruled out to make an accurate diagnosis. 

Diagnosis & Tests

Townes-Brocks syndrome is usually detected when a newborn is first examined by a physician. Diagnosis of Townes-Brocks syndrome is typically based on a clinical analysis of symptoms. Newborns who have the typical hallmarks of Townes-Brocks syndrome may receive a clinical diagnosis based on these findings, but identification of a mutation will confirm the clinical diagnosis.

Some patients with TBS have SALL1 mutations present but only a subset of symptoms that may make a clinical diagnosis more challenging. Molecular genetic testing is the best way to provide a definitive diagnosis as the clinical features of TBS can overlap with other conditions such as Fanconi anemia, oculo auriculo vertebral spectrum, and anus-hand-ear syndromes.

Genetic testing will check for mutations in the SALL1 gene to confirm a diagnosis. While most cases of TBS are discovered shortly after birth, a physician may suspect a child is affected if he or she does not develop bowel control by the age of three or has less common symptoms with a family history of Townes-Brocks syndrome. 

Treatment & Therapy

The primary treatment to manage Townes-Brocks syndrome involves immediate surgery to correct the imperforate anus followed by surgeries to correct malformations of the hands and/or feet. Imperforate anus can happen in many forms, including no anus, a rectum with openings to other structures such as the bladder or urethra, or a rectum that ends in a pouch without connecting to the colon. Surgical intervention will depend on the defect and may require repairing other structures of the body. A temporary colostomy bag is often required.

Congenital heart defects associated with TBS can be managed with routine care. A hearing evaluation is typically performed with early treatment of hearing loss provided to mitigate this loss. Laboratory and ultrasound tests are also routine to monitor kidney function.

In severe cases of kidney failure, kidney transplantation may be required. Heart defects may require surgical intervention with routine care provided by a cardiologist. While severe kidney and heart issues can be life-threatening and require serious intervention, most people with Townes-Brocks syndrome have a normal lifespan. 

Prevention & Prophylaxis

Townes-Brocks syndrome cannot be prevented, but genetic counseling can be helpful to families and individuals who are or may be affected by TBS.

In some cases, prenatal diagnosis of TBS is possible through chorionic villus sampling (CVS) or amniocentesis during pregnancy. Prenatal diagnosis is possible if classic malformations are visible on an ultrasound, in which case analysis of the unborn fetus's SALL1 gene can be conducted.