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Genetic and Rare Diseases Information Center (GARD)

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Townes-Brocks syndrome

Other Names for this Disease
  • Anus, imperforate, with hand, foot and ear anomalies
  • Deafness, sensorineural, with imperforate anus and hypoplastic thumbs
  • REAR syndrome
  • Renal-ear-anal-radial syndrome
  • TBS
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What is Townes-Brocks syndrome?

Townes-Brocks syndrome (TBS), or Renal-Ear-Anal-Radial (REAR) syndrome, is a multiple malformation syndrome. Characteristics are present at birth and vary from person to person. The most common characteristics include an absence of the anal opening (imperforate anus) and anomalies of the ears, hands, and feet. Hearing loss, malformations of the genital-renal system, craniofacial malformations, and mental retardation may also be present. This condition is extremely rare. Males and females are affected in equal numbers. [1]
Last updated: 9/5/2008

What are the signs and symptoms of Townes-Brocks syndrome?

Townes-Brocks syndrome (TBS) is characterized by the triad of imperforate anus (82%), dysplastic ears (88%) (overfolded superior helices and preauricular tags) frequently associated with sensorineural and/or conductive hearing impairment (65%), and thumb malformations (89%) (triphalangeal thumbs, duplication of the thumb (preaxial polydactyly), and rarely hypoplasia of the thumbs). [2] Most people with this condition have at least two of these three major features. [3]

In addition to these clinical features, the clinical manifestations of Townes-Brocks syndrome may include the following [2]:

  • Eyes.  Microphthalmia (rare), iris coloboma, lamellar cataract, chorioretinal coloboma with loss of vision

  • Kidneys.  Renal agenesis, renal hypoplasia, polycystic kidneys; functional impairment with or without structural abnormalities (42% of cases).

  • Hearing.  Congenital sensorineural and/or conductive hearing loss ranging from mild to severe. Hearing loss that is mild may worsen with age (65% of cases).

  • Heart.  Congenital heart disease occurs in 50% of persons with the common p.Arg276X mutations and 12%-25% of persons with other SALL1 mutations. Defects include atrial septal defect, ventricular septal defect, tetralogy of Fallot, lethal truncus arteriosus, pulmonary valve atresia, and persistent ductus arteriosus.

  • Gastrointestinal.  Anal stenosis, chronic constipation, gastroesophageal reflux.

  • Face.  Hemifacial microsomia.

  • Lower extremities.  Club foot, overlapping toes (II and IV over III), syndactyly of toes, missing toes (III) (52% of cases).

  • Genitourinary.  Hypospadias, vaginal aplasia with bifid uterus, bifid scrotum, cryptorchidism (36% of cases).

  • Central nervous system.

    • Mental retardation (about 10%)
    • Behavioral problems, observed in many children with TBS [Kohlhase, unpublished observations]
    • Arnold-Chiari malformation type I [Kohlhase, unpublished observations]
    • Cranial nerve palsy (nerves VI and VII)
    • Duane anomaly . Uni- or bilateral limitation of abduction of the eye associated with retraction of the globe and narrowing of the palpebral fissure on adduction. The abducens nucleus and nerve (cranial nerve VI) are absent and the lateral rectus muscle is innervated by a branch of the oculomotor nerve (cranial nerve III), accounting for the aberrant ocular movements
    • Hypoplasia of the dorsal part of corpus callosum
  • Skeletal.  Rib anomalies (fused ribs, missing ribs, additional cervical ribs), mild vertebral anomalies (9% of cases). Painful joints have been observed in several adults with TBS.

  • Endocrine.  Congenital hypothyroidism (rare)

  • Growth.  Postnatal growth retardation. This poorly documented feature has been described in fewer than 6% to 29% of persons reported with TBS in the literature. The occurrence of postnatal growth retardation among mutation-positive individuals is not known. 

Last updated: 9/5/2008

What genes are related to Townes-Brocks syndrome?

Mutations in the SALL1 gene cause Townes-Brocks Syndrome.

The SALL1 gene is part of a group of genes called the SALL family. These genes provide instructions for making proteins that are involved in the formation of tissues and organs before birth. SALL proteins act as transcription factors, which means they attach (bind) to specific regions of DNA and help control the activity of particular genes. Some mutations in the SALL1 gene lead to the production of an abnormally short version of the SALL1 protein that malfunctions within the cell. Other mutations prevent one copy of the gene in each cell from making any protein. It is unclear how these genetic changes disrupt normal development and cause the birth defects associated with Townes-Brocks syndrome. [3]

Last updated: 9/5/2008

How is Townes-Brocks syndrome diagnosed?

Townes-Brocks syndrome (TBS) is diagnosed clinically based on the presence of the following [2]:
  • Imperforate anus
  • Dysplastic ears (overfolded superior helices, microtia)
  • Typical thumb malformations (preaxial polydactyly, triphalangeal thumbs, hypoplastic thumbs) without shortening of the radius

SALL1 is the only gene known to be associated with TBS. Detection of a SALL1 mutation confirms the diagnosis. Direct sequencing of the complete SALL1 coding region and quantitative Real Time PCR analysis to identify intragenic and larger deletions are clinically available. [2]

Last updated: 9/5/2008

Is Townes-Brocks syndrome genetic?

Townes-Brocks syndrome is inherited in an autosomal dominant fashion, which means that in order for an individual to have this condition he/she has to inherit only one copy of the mutated gene from one of his/her parents. Many cases of this syndrome are sporadic (the first to occur in a family). [3]
Last updated: 9/5/2008

Is there treatment for Townes-Brocks syndrome?

Treatment is directed towards the specific symptoms, including immediate surgical intervention for imperforate anus; surgery for severe malformations of the hands; routine management of congenital heart defects; hemodialysis and possibly kidney transplantation for end-stage renal disease (ESRD); and early treatment of hearing loss. In addition, regular monitoring of renal function in individuals with and without renal anomalies, even if renal function is normal on initial examination should be conducted. [2]
Last updated: 9/5/2008

What is the prognosis for individuals with Townes-Brocks syndrome?

The prognosis is variable, as the condition has quite a bit of variation in expression. The prognosis depends on the scope of symptoms seen in each individual patient. Generally, the disorder becomes life-threatening only in cases of severe cardiac and renal malformations. [4]
Last updated: 9/5/2008