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Townes-Brocks syndrome

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Other Names:
TBS; Renal-ear-anal-radial syndrome; REAR syndrome; 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 See More
Categories:
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
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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 86 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Anal atresia
Absent anus
0002023
External ear malformation 0008572
Preauricular skin tag 0000384
Preaxial hand polydactyly
Extra thumb
0001177
Rectoperineal fistula 0004792
Rectovaginal fistula
Abnormal connection between rectum and vagina
0000143
Triphalangeal thumb
Finger-like thumb
0001199
30%-79% of people have these symptoms
Anteriorly placed anus 0001545
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Constipation 0002019
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Microtia
Small ears
Underdeveloped ears
[ more ] 		0008551
Overfolded helix
Overfolded ears
0000396
Pes planus
Flat feet
Flat foot
[ more ] 		0001763
Renal insufficiency
Renal failure
Renal failure in adulthood
[ more ] 		0000083
Subcutaneous nodule
Firm lump under the skin
Growth of abnormal tissue under the skin
[ more ] 		0001482
Toe clinodactyly 0001863
5%-29% of people have these symptoms
Abnormal pulmonary valve morphology 0001641
Abnormal vertebral morphology 0003468
Abnormality of the ribs
Rib abnormalities
0000772
Abnormality of the tragus 0009912
Abnormality of the uterus
Uterine abnormalities
Uterine malformations
[ more ] 		0000130
Abnormality of vision
Abnormality of sight
Vision issue
[ more ] 		0000504
Agenesis of corpus callosum 0001274
Aplasia/Hypoplasia of the 3rd toe
Absent/small 3rd toe
Absent/underdeveloped 3rd toe
[ more ] 		0010331
Arnold-Chiari malformation 0002308
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers
[ more ] 		0001631
Bifid scrotum
Cleft of scrotum
0000048
Blepharophimosis
Narrow opening between the eyelids
0000581
Bowel incontinence
Loss of bowel control
0002607
Broad hallux phalanx
Broad bone of big toe
Wide bone of big toe
[ more ] 		0010059
Broad thumb
Broad thumbs
Wide/broad thumb
[ more ] 		0011304
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Chorioretinal coloboma
Birth defect that causes a hole in the innermost layer at the back of the eye
0000567
Cranial nerve paralysis 0006824
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay
[ more ] 		0000823
Duane anomaly 0009921
Ectopic kidney
Abnormal kidney location
Displaced kidney
[ more ] 		0000086
Facial asymmetry
Asymmetry of face
Crooked face
Unsymmetrical face
[ more ] 		0000324
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Hypoplasia of penis
Underdeveloped penis
0008736
Hypospadias 0000047
Hypothyroidism
Underactive thyroid
0000821
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Iris coloboma
Cat eye
0000612
Limbal dermoid 0001140
Lower limb asymmetry
Left and right leg differ in length or width
0100559
Microphthalmia
Abnormally small eyeball
0000568
Multiple renal cysts
Multiple kidney cysts
0005562
Partial duplication of thumb phalanx
Partial duplication of the thumb bones
0009944
Patent ductus arteriosus 0001643
Renal hypoplasia
Small kidneys
Underdeveloped kidneys
[ more ] 		0000089
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Tetralogy of Fallot 0001636
Toe syndactyly
Fused toes
Webbed toes
[ more ] 		0001770
Ulnar deviation of finger
Finger bends toward pinky
0009465
Urethral valve 0010481
Vesicoureteral reflux 0000076
Wide mouth
Broad mouth
Large mouth
[ more ] 		0000154
1%-4% of people have these symptoms
Global developmental delay 0001263
Sensorineural hearing impairment 0000407
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Percent of people who have these symptoms is not available through HPO
2-3 toe syndactyly
Webbed 2nd and 3rd toes
0004691
2-4 finger syndactyly
Webbed index through ring fingers
0010709
3-4 finger syndactyly
Webbed 3rd-4th fingers
0006097
3-4 toe syndactyly
Webbed 3rd-4th toes
0009779
Anal stenosis
Narrowing of anal opening
0002025
Autosomal dominant inheritance 0000006
Bifid uterus 0000136
Clinodactyly of the 5th toe 0001864
Duodenal atresia
Absence or narrowing of first part of small bowel
0002247
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn
[ more ] 		0002020
Macrotia
Large ears
0000400
Metatarsal synostosis
Fusion of the long bones of the feet
0001440
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Multicystic kidney dysplasia 0000003
Overfolding of the superior helices 0004453
Preauricular pit
Pit in front of the ear
0004467
Pseudoepiphyses of second metacarpal
Extra bone on end of second long bone of hand
0006179
Renal dysplasia 0000110
Satyr ear 0030676
Short metatarsal
Short long bone of foot
0010743
Stahl ear 0100015
Umbilical hernia 0001537
Showing of 86 |
Last updated: 7/1/2020
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
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
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

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
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
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

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include VACTERL/VATER association, Okihiro syndrome, and Goldenhar syndrome (see these terms).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Townes-Brocks syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • I am wondering about Townes-Brock syndrome because I was born with this condition and I don't know anything about it. Can you provide me with all the information that you have on Townes-Brock syndrome? See answer


  1. Townes-Brocks Syndrome. Genetics Home Reference (GHR). 2007; http://ghr.nlm.nih.gov/condition/townes-brocks-syndrome.
  2. Kohlhase J. Townes-Brocks Syndrome. GeneReviews. 2016; http://www.ncbi.nlm.nih.gov/books/NBK1445/.
  3. Kohlhase J. Townes-Brocks syndrome. Orphanet. 2013; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=857.