The following information may help to address your question:
What is Townes-Brocks syndrome?
Townes-Brocks syndrome is a genetic condition characterized by an obstruction of the anal opening (imperforate anus), abnormally shaped ears, and thumb malformations. Most affected individuals have at least two of these three main features. Other signs and symptoms may include kidney abnormalities,
hearing loss,
heart defects, genital malformations and
intellectual disability. The condition is caused by
mutations in the
SALL1 gene which provides instructions for making
proteins that are involved in the formation of
tissues and
organs before birth. In rare cases, the syndrome may be caused by a mutation in the
SALL4 gene. Inheritance is
autosomal dominant.
[1] Imperforate anus is corrected with surgery as soon as possible, after the baby is born. The hearing loss should be treated early; the thumb malformation is also treated with surgery when needed.
[2]
Last updated: 10/24/2016
What are the signs and symptoms of Townes-Brocks syndrome?
Townes-Brocks syndrome is characterized by three main features:
[2][1]
- Imperforate anus (84% of the cases)
- Abnormally shaped ears (87% of the cases)
- Thumb malformations (89% of the cases) such as triphalangeal thumbs (when a thumb has 3 bones instead of 2 bones), duplication of the thumb (two tumbs), and rarely, very small thumbs).
Most people with this condition have at least two of these three major features.
[1]
Other frequent findings include:
[1]
- Hearing problems
- Kidney problems (such as end-stage renal disease (ESRD), which may occur with or without kidney malformations (malrotation, abnormal position (ectopia), abnormal shape (horseshoe kidney), small size (renal hypoplasia), multiple cysts in the kidney (polycystic kidneys), or vesicoutereral reflux).
- Congenital heart disease
- Foot malformations (flat feet, overlapping toes)
- Genital or urinary malformations
- Intellectual disability.
Rare features include eye anomalies (a defect on the iris of the eye (
iris coloboma), or an eye movement disorder known as
Duane anomaly),
Arnold-Chiari malformation type 1, and growth delay.
Visit
GeneReviews for more detailed information about the signs and symptoms of Townes-Brocks syndrome.
Last updated: 10/24/2016
What causes Townes-Brocks syndrome?
Townes-Brocks syndrome is caused by mutations in the
SALL1 gene. This
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. Some patients with the clinical features of the syndrome have a mutation in the SALL4 gene rather than SALL1 gene. It is unclear how these genetic changes disrupt normal development and cause the symptoms associated with Townes-Brocks syndrome.[1]
Last updated: 10/24/2016
How is Townes-Brocks syndrome diagnosed?
Townes-Brocks syndrome (TBS) is diagnosed when a patient has the following three major features:
[2][1]
- Imperforate anus
- Abnormally shaped ears
- Typical thumb malformations (two thumbs (preaxial polydactyly), triphalangeal thumbs which have three bones in them, much like the fingers, instead of the normal two, hypoplastic or underdeveloped thumbs) without shortening of the radius (the larger of the two bones in the forearm).
If only two major features are present, the presence of minor features and the absence of atypical features further support the diagnosis:
[2]
Minor features:
- Hearing impairment
- Foot malformations
- Kidney impairment with or without kidney malformations
- Genital or urinary malformations
- Congenital heart disease.
Atypical features (not suggestive of the syndrome):
- Radius hypoplasia on clinical examination or radiographs of the forearm
- Cleft lip/palate.
A
genetic test identifying a
mutation in the
SALL1 gene establishes the diagnosis if clinical features are inconclusive. A few patients with clinical features of the syndrome have a mutation in the
SALL4 gene. Therefore, people with a diagnosis of Townes-Brocks syndrome, who have a negative
SALL1 testing, should also have a
genetic testing for the
SALL4 gene.
[2]
Last updated: 10/24/2016
Is Townes-Brocks syndrome inherited?
Townes-Brocks syndrome is
inherited in an
autosomal dominant fashion, which means that one copy of the altered gene in each cell is sufficient to cause the disorder. In about 50% of cases, an affected person inherits the mutation from an affected parent. The other 50% have the condition as a result of a new (
de novo) mutation.
[2][1]
Last updated: 10/24/2016
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 thumbs, and early treatment of hearing loss. When heart defects are present, treatment is with the
routine management of
congenital heart defects, such as surgery and medication; Kidney impairment is treated with
hemodialysis and, in some cases, with kidney transplantation for
end-stage renal disease (ESRD). Regular monitoring of kidney function in individuals, with and without kidney anomalies, is recommended. An annual hearing testing is recommended.
[2]
Last updated: 10/24/2016
What is the prognosis for individuals with Townes-Brocks syndrome?
The
prognosis is variable; it depends on the symptoms present and their severity. Generally, when imperforate anus is treated early, the prognosis is good. The disorder becomes life-threatening only in cases of severe heart and kidney malformations.
[3]
Last updated: 10/24/2016
We hope this information is helpful. We strongly recommend you discuss this information with your doctor. If you still have questions, please
contact us.
Warm regards,
GARD Information Specialist
Please see our Disclaimer.
