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Cornelia de Lange Syndrome

Cornelia de Lange syndrome (CdLS) is a pan-ethnic disorder characterized by pre- and postnatal growth retardation and various congenital anomalies, including a facial gestalt, limb anomalies, gastrointestinal disorders, hirsutism, and intellectual disability. Mild to severe forms of CdLS have been observed. Approximately 37 to 47% of patients with CdLS have a mutation in the NIPBL […]

Cornelia de Lange syndrome (CdLS) is a pan-ethnic disorder characterized by pre- and postnatal growth retardation and various congenital anomalies, including a facial gestalt, limb anomalies, gastrointestinal disorders, hirsutism, and intellectual disability. Mild to severe forms of CdLS have been observed.

Approximately 37 to 47% of patients with CdLS have a mutation in the NIPBL gene identifiable by sequencing. Large deletions encompassing one or more exons of NIPBL have been identified in 5% of patients without mutations detectable by sequencing. The clinical course of patients with large deletions in the NIPBL gene, including growth and motor delay, is severe. NIPBL mutations are inherited in an autosomal dominant fashion.

SMC1A mutations have been observed in 5% of patients with CdLS and are composed mostly of missense and in-frame small deletions, and rarely of large in-frame deletions. Mutations in the SMC1A gene lead to mild to moderate phenotypes, including non-specific X-linked mental retardation. SMC1A mutations are X-linked; however, since SMC1A escapes inactivation, males and females with a mutation in SMC1A are affected.

Additionally, in 4-14% of patients with a clinical diagnosis of CdLS, a genomic deletion or duplication not including NIPBL or SMC1A was identified by karyotype or array CGH.

Tests Available

Prenatal Limb Abnormalities Panel

FORMS AND DOCUMENTS

TEST DETAILS

Genes:
NIPBL, SALL1, SALL4, TBX5, TP63 (TP73L)
Clinical Utility:
  • 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
Lab Method:
Exon Array CGH|Next-gen Sequencing

ORDERING

Test Code:
937
Turnaround Time:
3 weeks
Preferred Specimen:
20 mg CVS
Alternative Specimen:
20 mL Amniotic Fluid, 2 T25 flasks of cultured amniocytes, 2 T25 flasks of cultured chorionic villi, Ug DNA Concentration

BILLING

CPT Codes:
81405x1, 81479x4, 81265x1
New York Approved:
No
ABN Required:
Yes
Billing Information:
View Prenatal Billing Policy
* 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.

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