Rare Cardiology News

Disease Profile

Townes-Brocks syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

All ages

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ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

TBS; Renal-ear-anal-radial syndrome; REAR syndrome;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Ear, Nose, and Throat Diseases;

Summary

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] 

Symptoms

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.

 

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.

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

Cause

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]

Diagnosis

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]

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

    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]

    Organizations

    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.

    Learn more

    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.

        References

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

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