Townes–Brocks syndrome (TBS) is a rare

genetic disease A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

that has been described in approximately 200 cases in the published literature. It affects both males and females equally.Contact a Family
The condition was first identified in 1972. by Philip L. Townes, who was at the time a human geneticists and Professor of Pediatrics, and Eric Brocks, who was at the time a medical student, both at the University of Rochester.

Signs and symptoms

TBS patients may have the following symptoms: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). * Anorectal malformations, including

imperforate anus An imperforate anus or anorectal malformations (ARMs) are birth defects in which the rectum is malformed. ARMs are a spectrum of different congenital anomalies which vary from fairly minor lesions to complex anomalies. The cause of ARMs is unkno ...

/absence of an anal opening,

rectovaginal fistula A rectovaginal fistula is a medical condition where there is a fistula or abnormal connection between the rectum and the vagina. Rectovaginal fistulae may be extremely debilitating. If the opening between the rectum and vagina is wide it will allo ...

, anal stenosis, unusually placed anus. * Kidney abnormalities, sometimes leading to impaired kidney function or

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

, including hypoplastic kidneys (underdeveloped), multicystic kidneys, dysplastic kidneys. * Heart abnormalities, including

tetralogy of fallot Tetralogy of Fallot (TOF), formerly known as Steno-Fallot tetralogy, is a congenital heart defect characterized by four specific cardiac defects. Classically, the four defects are: *pulmonary stenosis, which is narrowing of the exit from the r ...

and defects of the

ventricular septum The interventricular septum (IVS, or ventricular septum, or during development septum inferius) is the stout wall separating the ventricles, the lower chambers of the heart, from one another. The ventricular septum is directed obliquely backwar ...

. * Hand and foot abnormalities, such as

hypoplastic Hypoplasia (from Ancient Greek :wikt:ὑπό, ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.syndactyly Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and diprotodontia, but is an unusual condition in humans. The term is from Greek σύν, ''syn'' 'together' and δά� ...

(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. 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.

Causes

TBS is an autosomal dominant involving the a mutation of the gene

SALL1 Sal-like 1 (Drosophila), also known as SALL1, is a protein which in humans is encoded by the ''SALL1'' gene. As the full name suggests, it is one of the human versions of the ''spalt'' (''sal'') gene known in ''Drosophila''. Function The prote ...

, which encodes a transcriptional repressor which interacts with TRF1/PIN2 and localizes to pericentromeric heterochromatin. The clinical features of TBS overlap with VATER and

VACTERL The VACTERL association (also VATER association, and less accurately VACTERL syndrome) refers to a recognized group of birth defects which tend to co-occur (see below). This pattern is a recognized association, as opposed to a syndrome, because t ...

associations, oculo-auriculo-vertebral (OAV) spectrum, branchio-oto-renal (BOR) syndrome, and

Fanconi anemia Fanconi anaemia (FA) is a rare genetic disease resulting in impaired response to DNA damage. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of no ...

and other 'anus-hand-ear' syndromes.GeneDX
Although some symptoms can be life-threatening, many people diagnosed with Townes-Brocks Syndrome live a normal lifespan.

Diagnosis

Treatment

Notes

External links

GeneReview/NCBI/NIH/UW entry on Townes-Brocks Syndrome
{{DEFAULTSORT:Townes-Brocks Syndrome Genodermatoses Rare diseases Syndromes affecting the heart Syndromes affecting hearing Syndromes affecting the gastrointestinal tract