Townes-Brocks syndrome
Encyclopedia
Townes–Brocks syndrome is a rare genetic disease that affects fewer than 200 people in the entire world. It affects both males and females equally. The condition was first identified in 1972.
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.
, 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 associations, oculo-auriculo-vertebral (OAV) spectrum, branchio-oto-renal (BOR) syndrome, and Fanconi anemia
and other 'anus-hand-ear' syndromes.
Although some symptoms can be life-threatening, many people diagnosed with Townes-Brocks Syndrome live a normal lifespan.
Symptoms
TBS sufferers may have the following symptoms:- Abnormalities of the external ears (unusually large or small, unusually shaped, sometimes with sensorineural hearing lossSensorineural hearing lossSensorineural hearing loss is a type of hearing loss in which the root cause lies in the vestibulocochlear nerve , the inner ear, or central processing centers of the brain....
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 anusImperforate anusAn imperforate anus or anal atresia is a birth defect in which the rectum is malformed. Its cause is unknown.-Features:There are several forms of imperforate anus:* A low lesion, in which the colon remains close to the skin...
/absence of an anal opening, rectovaginal fistulaRectovaginal fistulaA rectovaginal fistula is a medical condition where there is a fistula or abnormal connection between the rectum and the vagina. Rectovaginal fistula may be extremely debilitating. If the opening between the rectum and vagina is wide it will allow both flatulence and feces to escape through the...
, anal stenosisStenosisA stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure.It is also sometimes called a stricture ....
, 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 fallotTetralogy of FallotTetralogy of Fallot is a congenital heart defect which is classically understood to involve four anatomical abnormalities...
and defects of the ventricular septum.
- Hand and foot abnormalities, such as hypoplastic thumbs, fingerlike thumbs, syndactylySyndactylySyndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and kangaroo, but is an unusual condition in humans.-Classification:...
(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 SALL1SALL1
Sal-like 1 , 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 gene known in Drosophila.- Function :...
, which encodes a transcriptional repressor which interacts with TRF1/PIN2 and localizes to pericentromeric heterochromatin
Heterochromatin
Heterochromatin is a tightly packed form of DNA, which comes in different varieties. These varieties lie on a continuum between the two extremes of constitutive and facultative heterochromatin...
. The clinical features of TBS overlap with VATER
Vater
Vater Percussion is an American drumstick and percussion accessory manufacturing company. It was founded by Clarence Vater, and is currently run by his two grandsons Alan and Ron Vater. Although the company began producing sticks in 1956, it did not officially become Vater Percussion until much later...
and VACTERL associations, oculo-auriculo-vertebral (OAV) spectrum, branchio-oto-renal (BOR) syndrome, and Fanconi anemia
Fanconi anemia
Fanconi anemia is a genetic disease with an incidence of 1 per 350,000 births, with a higher frequency in Ashkenazi Jews and Afrikaners in South Africa.FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair...
and other 'anus-hand-ear' syndromes.
Although some symptoms can be life-threatening, many people diagnosed with Townes-Brocks Syndrome live a normal lifespan.