What are the other Names for this Condition? (Also known as/Synonyms)

• Imperforate Anus with Hand, Foot, and Ear Anomalies
• Renal-Ear-Anal-Radial Syndrome
• Sensorineural Deafness with Imperforate Anus and Hypoplastic Thumbs

What is Townes-Brocks Syndrome? (Definition/Background Information)

• Townes-Brocks Syndrome (TBS) is a rare genetic disorder that is mostly characterized by a set of signs and symptoms that include absent or blocked anal opening, hand and foot abnormalities, and hearing loss. Some children also present kidney and/or heart defects
• Townes-Brocks Syndrome follows an autosomal dominant inheritance pattern and is caused by the inheritance of a mutated SALL1 gene. In rare cases, a family history of the disorder may be a risk factor for TBS
• A healthcare professional can diagnose Townes-Brocks Syndrome with a complete physical examination, family history evaluation, along-with molecular genetic testing to confirm the diagnosis. A delayed diagnosis can lead to severe heart and kidney complications
• There are currently no known prevention methods for Townes-Brocks Syndrome. However, the disorder may be adequately managed via corrective surgeries, use of hearing aids, and treating any complications that may arise

Who gets Townes-Brocks Syndrome? (Age and Sex Distribution)

• Townes-Brocks Syndrome is a rare congenital condition that can affect both males and females
• Worldwide, all racial and ethnic backgrounds may be affected

What are the Risk Factors for Townes-Brocks Syndrome? (Predisposing Factors)

• A positive family history of Townes Brocks Syndrome may be an important risk factor
• Currently, no other risk factors have been clearly identified for this disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Townes-Brocks Syndrome? (Etiology)

Townes-Brocks Syndrome is caused by the inheritance of a mutated form of the SALL1 gene. In some cases, the involvement of the SALL4 gene is noted.

• The disorder follows an autosomal dominant inheritance pattern, meaning that only one copy of the mutated gene is needed to be affected
• This gene may be inherited from one parent (observed in rare cases), or arise from spontaneous mutation during embryonic development

Autosomal dominant mode of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Townes-Brocks Syndrome?

The signs and symptoms of Townes-Brocks Syndrome may vary from one child to another, and may include:

• Imperforate anus: An absent (or blocked) anal opening
• Small ears and folded skin around the outer ear cartilage 
• Hearing loss that may get progressively worse
• Triphalangeal thumbs: Thumbs containing three bones (phalanges) instead of two
• Flat feet, overlapping toes, and a short third toe
• Urogenital malformation and kidney abnormalities
• Congenital heart defects
• Cognitive impairment

How is Townes-Brocks Syndrome Diagnosed?

Townes-Brocks Syndrome may be diagnosed through the following tests and exams:

• Complete physical examination and comprehensive evaluation of family medical history
• Assessment of the presenting signs and symptoms
• Hearing and vision assessment
• Assessment of cardiac function
• Kidney function tests
• Radiological imaging studies of the affected regions:
  • X-rays to assess skeletal abnormalities of the hands and feet
  • Abdominal ultrasound scan
  • Echocardiogram to detect any defects in the heart
  • CT or MRI scans, as needed
• Molecular genetic testing to look for a mutated SALL1 or SALL4 gene

The following diagnostic criteria is adopted for Townes-Brocks Syndrome (TBS):

• Major features:
  • Imperforate anus
  • Ear abnormalities (structural abnormalities)
  • Thumb malformations such as triphalangeal thumbs or two (conjoined) thumbs
• Minor features:
  • Hearing loss
  • Foot defects
  • Reduced kidney function with/without kidney defects
  • Urinary and genital defects
  • Congenital heart anomalies
• Atypical features:
  • Hypoplasia of the radius bone (forearm bone)
  • Cleft lip and/or palate

TBS may be confirmed by a presence of ALL three major features OR, two major features with the minor features, AND showing an absence of the atypical features.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Townes-Brocks Syndrome?

The complications of Townes-Brocks Syndrome may include:

• Emotional stress for parents and caregivers
• Growth delays
• Difficulties with daily tasks due to physical malformations
• Improper filtration of the urine due to kidney abnormalities
• Other kidney-related issues such as polycystic kidney disease, renal hypoplasia, and vesicoureteral reflux
• Severe heart anomalies
• Mental health retardation
• In rare cases, eye abnormalities such as iris coloboma or Duane anomaly
• Arnold-Chiari malformation type 1
• Reduced quality of life

How is Townes-Brocks Syndrome Treated?

The treatment interventions of Townes-Brocks Syndrome include:

• Corrective surgery to fix malformations in the anus, hands, ears, feet, kidney, and spine
• Use of hearing aids, as required
• Physiotherapy
• Medications and other treatment options to manage associated complications
• Behavior modification, as necessary

Regular medical screening at periodic intervals with tests and physical examinations are necessary and highly recommended.

How can Townes-Brocks Syndrome be Prevented?

Townes-Brocks Syndrome may not be preventable since many of these genetic disorders are diagnosed at or following the birth of the child.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Townes-Brocks Syndrome? (Outcomes/Resolutions)

The prognosis for Townes-Brocks Syndrome depends upon the type and severity of the associated signs and symptoms.

• An early diagnosis and prompt medical treatment can greatly improve the prognosis
• With appropriate treatments, children with mild conditions do better than those with severe symptoms
• Children with severe heart, kidney, and other defects may have worse outcomes

Additional and Useful Relevant Information for Townes-Brocks Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/