Townes-Brocks Syndrome

Townes-Brocks syndrome is a rare multiple malformation syndrome characterized by anal, limb, ear, and renal anomalies. Intelligence is normal in most affected individuals. Diagnostic features include ano-rectal abnorma-lities (imperforate or anteriorly placed anus, anal stenosis, prominent midline perineal raphe); abnormalities of the hands and feet (preaxial polydactyly, triphalangeal thumbs, bifid thumbs and toes, finger and toe syndactyly); external ear malformations (preauricular tags or pits, “lop” or “satyr” ear, microtia, abnormal helix) with hearing loss (sensorineural, conductive or mixed); and renal anomalies leading to impaired renal function or renal failure (unilateral or bilateral hypoplastic or dysplastic kidneys, multicystic kidneys, renal agenesis, posterior urethral valves, vesicouretal reflex). Other, less common features are cardiac defects, mental retardation, eye, genitourinary and vertebral abnormalities, hypothyroidism, umbilical hernia, and gastroesophageal reflux. The intra- and interfamilial clinical presentation of TBS varies widely and overlaps with several other disorders including VATER and VACTERL associations, Okihiro syndrome, Fanconi anemia, Baller-Gerold syndrome, branchio-oto-renal (BOR) syndrome and oculo-auriculo-vertebral (OAV) spectrum. Important differentiating characteristics of TBS are the absence of radial hypoplasia, craniosynostosis, and tracheo-esophageal fistula. Prenatal full gene sequence analysis is available when fetal ultrasound abnormalities are suggestive of TBS.

Tests Available

Forms and Documents

Test Details

SALL1
  • Prenatal diagnosis based on fetal ultrasound abnormalities
  • Mutation-specific testing for fetuses with a family history of a known SALL1 mutation
  • Capillary Sequencing

Ordering

2523
2-3 weeks
20 mL Amniotic Fluid
20 mg CVS|2 T25 flasks of cultured amniocytes|2 T25 flasks of cultured chorionic villi|3 Ug DNA Concentration

Billing

81479x1, 81265x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Botzenhart, E. et al., Human Mutation 26:282, 2005
  2. Kohlhase, J. et al., Am J Hum Genet. 64: 435-445, 1999
  3. Marlin, S. et al., Human Mutation 14: 377-386, 1999
  4. Borozdin, W. et al., Human Mutation 867 (Online) 2006

Forms and Documents

Test Details

SALL1
  • Confirmation of a clinical diagnosis
  • Risk assessment
  • Prenatal diagnosis - in families with an affected child and known mutation
  • Capillary Sequencing

Ordering

2521
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Marlin, S. et al., Human Mutation 14: 377-386, 1999
  2. Kohlhase, J. et al., Am J Hum Genet. 64: 435-445, 1999
  3. Borozdin, W. et al., Human Mutation 867 (Online) 2006
  4. Botzenhart, E. et al., Human Mutation 26:282, 2005

Forms and Documents

Test Details

NIPBL, SALL1, SALL4, TBX5, TP73L (TP63)
  • Prenatal diagnosis in a fetus based on ultrasound findings suggestive of a limb abnormality syndrome
  • Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Distinguish between causes and forms of limb abnormality syndromes
  • Genetic counseling, especially regarding recurrence risk
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

937
3 weeks
20 mg CVS
20 mL Amniotic Fluid|2 T25 flasks of cultured amniocytes|2 T25 flasks of cultured chorionic villi|3 ug DNA Concentration

Billing

81405x1, 81479x4, 81265x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Urban M, et al. Am J Med Genet. 2001 Jul 22;102(1):73-5.
  2. Huang WH, Porto M. Obstet Gynecol. 2002 May;99(5 Pt 2):956-8.
  3. Clark DM, et al. Am J Med Genet A. 2012 Aug;158A(8):1848-56. doi: 10.1002/ajmg.a.35410. Epub 2012 Jun 27.
  4. Kohlhase (Updated May 2012). Townes-Brocks Syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.org.
  5. Kohlhase (Updated January 2015). SALL4-Related Disorders. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. available at http://www.genetests.org.
  6. Tongsong T, Chanprapaph P., J Clin Ultrasound. 2000; 28: 98–100.
  7. Sepulveda W, Enriquez G, Martinez JL, Mejia R., J Ultrasound Med. 2004; 23: 983–7.
  8. Sutton VR, van Bokhoven H. TP63-Related Disorders. 2010 Jun 8 [Updated 2015 Aug 6]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  9. Kline et al. (1993) Am J Med Genet 47:1042-1049.
  10. McDermott, D. et al., Pediatr Res. 58: 981-86, 2005.
  11. Gillis et al. (2004) Am J Hum Genet 75:610-623.
  12. Borck et al. (2006) Hum Mutat 27:731-735.
  13. Minor et al. (2014) Gene537:279-284.
  14. Castronovo et al. (2010) Clin Genet 78:560-564.
  15. Niu et al. (2006) Prenat Diagn 26:1054-1057.
  16. Weichert et al. (2011) J Mat Fetal Neonat Med 24(7):978-982.
  17. Botzenhart, E. et al., Human Mutation 26:282, 2005.
  18. Miertus, J. et al., Hum Genet. 119: 154-161, 2006.
  19. Marlin, S. et al., Human Mutation 14: 377-386, 1999.
  20. Borozdin, W. et al., Human Mutation 867(Online) 2006.
  21. Borozdin, W. et al., J Med Genet. 41(9):e113, 2004.
  22. Kohlhase J. et al., J Med Genet. 40:473-478, 2003.
  23. Akrami, SM. et al. J Med Genet. 38:E44, 2001.
  24. Fan, C. et al. J Med Genet. 40:e29, 2003.
  25. Borozdin, W. et al. Hum Mutat. 27:975-976, 2006.