Townes-Brocks Syndrome
| Classification according to ICD-10 | |
|---|---|
| Q87.8 | Other specified congenital malformation syndromes, not elsewhere classified |
| ICD-10 online (WHO version 2019) | |
The Townes-Brocks syndrome is an autosomal - dominant inherited combination of malformations of the ears, the anus and the thumb. About half of the cases are also associated with kidney malformations.
distribution
The syndrome occurs comparatively rarely, the average probability of occurrence is around 1–9: 1,000,000, although in the majority of cases it arises sporadically due to a new mutation (no figures are available yet).
root cause
Townes-Brocks syndrome is caused by changes ( mutations ) in the SALL1 gene (hereditary disposition) on chromosome 16q12.1 , which are found in around 70 out of 100 people who are clinically clearly affected, i.e. show the typical malformations.
Townes-Brocks syndrome can sometimes be confused with Okihiro syndrome . It is caused by defects in the similar SALL4 gene on chromosome 20 . The syndrome is characterized by thumb malformations (as in Townes-Brocks syndrome) with shortening of the radius in combination with a Duane anomaly. But there can also be ear malformations, kidney malformations and anal atresia.
Another possibility of confusion is the so-called VACTERL association, a combination of vertebral (columnar) defects, anal atresia, heart defects, malformations of the esophagus and trachea, kidneys and limbs. The cause of this combination is still unknown.
Symptoms
Characteristic is a combination of ear malformations, anal atresia and thumb malformations (tripartite thumbs, excess thumbs, but no shortening of the radius ). There are kidney malformations in approx. 50% and kidney dysfunction (even if the kidneys are not malformed) up to kidney failure . Deafness is common (approx. 80%), heart defects are not uncommon (approx. 25%, with the most common mutation R276X even 50%). Some affected children are developmentally retarded or have behavioral problems (<10%). Occasionally there are facial asymmetries.
forecast
The life expectancy of people with Townes-Brocks syndrome is not reduced if there is no severe impairment of the kidneys and heart. About 50% of the diseases that first appeared in a family (so-called sporadic cases) are caused by a single genetic defect , the R276X mutation. This seems to be associated with a lower probability of survival, because so far only one family is known in which this mutation has occurred in two generations, while it is common with other mutations.
Monitoring kidney function is extremely important. For many people, dialysis treatment and a kidney transplant may become necessary in adulthood. If Townes-Brocks syndrome is suspected, a hearing test should be done at an early stage. The correction of the heart defect and the correction of the malformations of the extremities are also of therapeutic importance.
literature
- J. Kohlhase, A. Wischermann, H. Reichenbach, U. Froster, W. Engel: Mutations in the SALL1 putative transcription factor gene cause Townes-Brocks syndrome. In: Nature Genetics. 1998; 18, pp. 81-83.
- WS Surka, J. Kohlhase, CE Neunert, DS Schneider, VK Proud: Unique family with Townes-Brocks syndrome, SALL1 mutation, and cardiac defects. In: Am. J. Med. Genet. 2001, 102, pp. 250-257.
- J. Kohlhase, M. Liebers, J. Backe, A. Baumann-Müller, M. Bembea, A. Destrée, M. Gattas, S. Grüßner, T. Müller, G. Mortier, C. Skrypnyk, S. Yano, J. Wirbelauer, RC Michaelis: High incidence of the R276X SALL1 mutation in sporadic but not familial Townes-Brocks syndrome and report of the first familial case. In: J Med Genet. 2003; 40, p. E127.
- J. Kohlhase: Townes-Brocks syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource. [database online] 2007; Available at [1]