Townes-Brocks syndrome
| Townes-Brocks syndrome |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and Related keywords: Anal-ear-renal-radial malformation syndrome, deafness-imperforate anus-hypoplastic thumbs syndrome, imperforate anus-hand and foot anomalies syndrome, renal-ear-anal-radial syndrome (REAR), sensorineural deafness-imperforate anus-hypoplastic thumbs syndrome, Townes syndrome
Overview
Townes-Brocks syndrome (TBS) is a genetic condition that affects several parts of the body. The most common features of this condition are an obstruction of the anal opening (imperforate anus), abnormally shaped ears, and hand malformations that most often affect the thumb. Most people with this condition have at least two of these three major features.
The prevalence of this condition is unknown, although one study estimated that it may affect 1 in 250,000 people. It is difficult to determine how frequently Townes-Brocks syndrome occurs because the varied signs and symptoms of this disorder overlap with those of other genetic syndromes. It affects both males and females equally.[1] The condition was first identified in 1972.[1]
Genetics and Etiology
TBS is an autosomal dominant multiple malformation disorder involving the a mutation of the gene SALL1, which encodes a transcriptional repressor which interacts with TRF1/PIN2 and localizes to pericentromeric heterochromatin. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. Mutations in the SALL1 gene cause Townes-Brocks Syndrome.
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.[2] 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. It is unclear how these genetic changes disrupt normal development and cause the birth defects associated with Townes-Brocks syndrome.
Although some symptoms can be life-threatening, many people diagnosed with Townes-Brocks Syndrome live a normal lifespan.[1]
Symptoms
TBS sufferers may have the following symptoms:[3]
- 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 abnormalities, i.e. malformations of the anus, 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.
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.