Other Names: TBS; Renal-ear-anal-radial syndrome; REAR syndrome; Anus, imperforate, with hand, foot and ear anomalies; Deafness, sensorineural, with imperforate anus and hypoplastic thumbs; Imperforate anus with hand, foot and ear anomalies; Sensorineural deafness with imperforate anus and hypoplastic thumbs; Townes syndrome; Imperforate anus-hand, foot and ear anomalies syndrome
== Townes–Brocks Syndrome ==
{{Infobox medical condition (new)
[[File:Autosomal_dominant_-_en.svg|thumb|right|Diagram of autosomal dominant inheritance pattern.]]
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| image = Autosomal dominant - en.svg
| caption = This condition is inherited in an autosomal dominant manner
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'''Townes–Brocks syndrome'''<ref name="Bolognia">{{cite book |author=Rapini, Ronald P. |author2=Bolognia, Jean L. |author3=Jorizzo, Joseph L. |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |pages=894 |isbn=1-4160-2999-0 |oclc= |doi= |accessdate=}}</ref> ('''TBS''') is a rare [[genetic disease]] that has been described in approximately 200 cases in the published literature. It affects both males and females equally.<ref name="cafamily">[http://www.cafamily.org.uk/Direct/t26.html Contact a Family] {{Webarchive|url=https://web.archive.org/web/20060924151240/http://www.cafamily.org.uk/Direct/t26.html |date=2006-09-24 }}</ref> The condition was first identified in 1972.<ref name="cafamily"/> by [[Philip L. Townes]], MD, PhD, who was at the time a human geneticists and Professor of Pediatrics, and Eric Brocks, MD, who was at the time a medical student, both at the University of Rochester.
==Symptoms==
'''Townes–Brocks syndrome''' (TBS) is a rare [[genetic disorder]] characterized by a triad of [[congenital anomalies]]: [[anorectal malformations]], [[ear abnormalities]], and [[thumb malformations]]. It is an [[autosomal dominant]] condition, meaning that a single copy of the altered gene in each cell is sufficient to cause the disorder.
TBS patients may have the following symptoms:<ref name="rarediseases">[http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Townes%20Brocks%20Syndrome National Organization for Rare Diseases]</ref>
*Abnormalities of the external ears (unusually large or small, unusually shaped, sometimes with [[sensorineural hearing loss]] or deafness due to lesions or dysfunctions of part of the internal ear or its nerve tracts and centers or conductive hearing loss from the external or middle ear), dysplastic ears, lop ear (over-folded ear helix), preauricular tags or pits (a rudimentary tag of ear tissue typically located just in front of the ear).
=== Etiology ===
*[[Anorectal malformation]]s, including [[imperforate anus]]/absence of an anal opening, [[rectovaginal fistula]], anal [[stenosis]], unusually placed anus.
*Renal abnormalities, sometimes leading to impaired renal function or renal failure, including [[hypoplastic]] kidneys (underdeveloped), multicystic kidneys, dyspastic kidneys.
*Heart abnormalities, including [[tetralogy of fallot]] and defects of the [[ventricular septum]].
*Hand and foot abnormalities, such as [[hypoplastic]] thumbs, fingerlike thumbs, [[syndactyly]] (webbed fingers/toes), fusion of the wrist bones, overlapping foot and/or toe bones.
Learning difficulties have been reported in some children with TBS. For others, intelligence is within the normal range.
Townes–Brocks syndrome is caused by mutations in the [[SALL1]] gene, which provides instructions for making a protein that is involved in the development of many parts of the body. The SALL1 protein is a transcription factor that regulates the activity of other genes, particularly during embryonic development.
These abnormalities, which are present prenatally, can range from minor to severe, and as with similar disorders, most individuals with this condition have some, but not all, of these traits.
=== Clinical Features ===
==Causes==
The clinical presentation of Townes–Brocks syndrome can vary widely among affected individuals, even within the same family. The most common features include:
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 [[protein]]s that are involved in the '''formation of tissues and organs before birth'''. SALL proteins '''act as [[transcription factor]]s''', 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.
==Diagnosis==
* '''Anorectal malformations''': These can range from mild anal stenosis to more severe forms such as imperforate anus.
Townes-Brocks syndrome (TBS) is diagnosed when a patient has the following three major features:
* '''Ear abnormalities''': These may include preauricular tags, hearing loss, and structural ear defects.
[[Imperforate]] anus
* '''Thumb malformations''': These can include triphalangeal thumbs, duplicated thumbs, or hypoplastic thumbs.
* 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:
Other possible features include [[renal anomalies]], [[cardiac defects]], and [[genitourinary abnormalities]].
'''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):'''
=== Diagnosis ===
* [[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.
Diagnosis of Townes–Brocks syndrome is based on clinical findings and can be confirmed by genetic testing to identify mutations in the SALL1 gene. Prenatal diagnosis is possible if the mutation in the family is known.
==Treatment==
=== Management ===
Treatment
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.
== '''Prognosis''' ==
Management of Townes–Brocks syndrome is symptomatic and supportive. It may involve surgical correction of anorectal malformations, hearing aids for hearing loss, and orthopedic interventions for limb anomalies. Regular monitoring of renal function and cardiac health is also recommended.
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.
==Notes==
== Related Pages ==
<references/>
== External links ==
* [[Genetic disorder]]
{{Medical resources
* [[Autosomal dominant]]
| DiseasesDB = 32163
* [[Congenital anomaly]]
| ICD10 ={{ICD10|Q|87|8|q|87}}
* [[SALL1]]
| ICD9 =
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| OMIM = 107480
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*[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=tbs GeneReview/NCBI/NIH/UW entry on Townes-Brocks Syndrome]
{{Transcription factor/coregulator deficiencies}}
{{Genetic disorders}}
{{DEFAULTSORT:Townes-Brocks Syndrome}}
[[Category:Genetic disorders]]
[[Category:Genodermatoses]]
[[Category:Congenital disorders]]
[[Category:Rare diseases]]
[[Category:Syndromes affecting the heart]]
[[Category:Syndromes affecting hearing]]
[[Category:Syndromes affecting the gastrointestinal tract]]
Townes–Brocks syndrome is caused by mutations in the SALL1 gene, which provides instructions for making a protein that is involved in the development of many parts of the body. The SALL1 protein is a transcription factor that regulates the activity of other genes, particularly during embryonic development.
Clinical Features
The clinical presentation of Townes–Brocks syndrome can vary widely among affected individuals, even within the same family. The most common features include:
Anorectal malformations: These can range from mild anal stenosis to more severe forms such as imperforate anus.
Ear abnormalities: These may include preauricular tags, hearing loss, and structural ear defects.
Thumb malformations: These can include triphalangeal thumbs, duplicated thumbs, or hypoplastic thumbs.
Diagnosis of Townes–Brocks syndrome is based on clinical findings and can be confirmed by genetic testing to identify mutations in the SALL1 gene. Prenatal diagnosis is possible if the mutation in the family is known.
Management
Management of Townes–Brocks syndrome is symptomatic and supportive. It may involve surgical correction of anorectal malformations, hearing aids for hearing loss, and orthopedic interventions for limb anomalies. Regular monitoring of renal function and cardiac health is also recommended.
