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 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

Forms and Documents

Test Details

HDAC8, NIPBL, RAD21, SMC1A, SMC3
  • Diagnosis in a patient based on clinical or radiographic findings suggestive of a skeletal dysplasia
  • Diagnosis for known familial pathogenic variant(s)
  • Distinguish between causes and forms of skeletal dysplasias
  • Genetic counseling, especially regarding recurrence risk
  • Next-Gen Sequencing
  • Exon Array CGH

Ordering

584
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)

Billing

81479x5
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Kline et al. (1993) Am J Med Genet 47:1042-1049.
  2. Deardorff MA, Clark DM, Krantz ID. 2005 [updated 2011 Oct 27]. Cornelia de Lange Syndrome. In: Pagon RA, Bird TD, Dolan CR, Stephens K. GeneReviews [Internet].
  3. Oliveira et al. (2010) Hum Mutat 31(11):1216-1222.
  4. Castronovo et al. (2010) Clin Genet 78:560-564.
  5. Niu et al. (2006) Prenat Diagn 26:1054-1057.
  6. Weichert et al. (2011) J Mat Fetal Neonat Med 24(7):978-982.
  7. Deardorff et al. (2007) Am J Hum Genet 80:485-494.
  8. Bhuiyan et al. (2007) Eur J Hum Genet 15:505-508.
  9. Ratajska et al. (2010) Eur J Med Genet 53:378-382.
  10. DeScipio et al. (2005) Am J Med Gen 137A:276-282.
  11. Yan et al. (2009) J Med Genet 46:626-634.
  12. Pie et al. (2010) Am J Med Genet 152A(4):924-929.
  13. Selicorni et al. (2007) Clin Genet 72:98-108.
  14. Gillis et al. (2004) Am J Hum Genet 75:610-623.
  15. Borck et al. (2006) Hum Mutat 27:731-735.
  16. Yan et al., (2006) Am J Med Genet 140A:1531-1541
  17. Borck et al., (2004) J Med Genet 41:e128.
  18. Schoumans et al., (2007) Eur J Hum Genet 15:143-149.
  19. Gervasini et al., (2008) Clin Genet 74:531-538.
  20. Hoppman-Chaney et al., (2011) Am J Med Genet Part A 158A:193-98.
  21. 21. Deardorff MA, et al. (2012) Nature. Sep 13;489(7415):313-7. PMID: 22885700

Forms and Documents

Test Details

NIPBL
  • Confirmation of a clinical diagnosis
  • Prenatal diagnosis in a family with a known mutation
  • Capillary Sequencing

Ordering

569
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Brushes

Billing

81479x1
No
Yes
  • 759.89 Other Congenital malformation syndromes affecting multiple systems
  • 783.43 Short stature, Growth failure, Growth retardation, Lack of growth, Physical retardation
  • 319 Unspecified mental retardation, Mental deficiency NOS, Mental subnormality NOS
  • 755.20 Unspecified reduction deformity of upper limb Ectromelia NOS of upper limb Hemimelia NOS of upper limb Shortening of arm, congenital
* For price inquiries please email zebras@genedx.com

References

  1. Kline et al. (1993) Am J Med Genet 47:1042-1049.
  2. Deardorff MA, Clark DM, Krantz ID. 2005 [updated 2011 Oct 27]. Cornelia de Lange Syndrome. In: Pagon RA, Bird TD, Dolan CR, Stephens K. GeneReviews [Internet].
  3. Oliveira et al. (2010) Hum Mutat 31(11):1216-1222.
  4. Castronovo et al. (2010) Clin Genet 78:560-564.
  5. Niu et al. (2006) Prenat Diagn 26:1054-1057.
  6. Weichert et al. (2011) J Mat Fetal Neonat Med 24(7):978-982.
  7. Deardorff et al. (2007) Am J Hum Genet 80:485-494.
  8. Bhuiyan et al. (2007) Eur J Hum Genet 15:505-508.
  9. Ratajska et al. (2010) Eur J Med Genet 53:378-382.
  10. DeScipio et al. (2005) Am J Med Gen 137A:276-282.
  11. Yan et al. (2009) J Med Genet 46:626-634.
  12. Pie et al. (2010) Am J Med Genet 152A(4):924-929.
  13. Selicorni et al. (2007) Clin Genet 72:98-108.
  14. Gillis et al. (2004) Am J Hum Genet 75:610-623.
  15. Borck et al. (2006) Hum Mutat 27:731-735.
  16. Yan et al., (2006) Am J Med Genet 140A:1531-1541
  17. Borck et al., (2004) J Med Genet 41:e128.
  18. Schoumans et al., (2007) Eur J Hum Genet 15:143-149.
  19. Gervasini et al., (2008) Clin Genet 74:531-538.
  20. Hoppman-Chaney et al., (2011) Am J Med Genet Part A 158A:193-98.

Forms and Documents

Test Details

NIPBL
  • Confirmation of a clinical diagnosis
  • Prenatal diagnosis in a family with a known mutation
  • Capillary Sequencing

Ordering

568
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Brushes

Billing

81479x1
No
Yes
  • 759.89 Other Congenital malformation syndromes affecting multiple systems
  • 783.43 Short stature, Growth failure, Growth retardation, Lack of growth, Physical retardation
  • 319 Unspecified mental retardation, Mental deficiency NOS, Mental subnormality NOS
  • 755.20 Unspecified reduction deformity of upper limb Ectromelia NOS of upper limb Hemimelia NOS of upper limb Shortening of arm, congenital
* For price inquiries please email zebras@genedx.com

References

  1. Kline et al. (1993) Am J Med Genet 47:1042-1049.
  2. Deardorff MA, Clark DM, Krantz ID. 2005 [updated 2011 Oct 27]. Cornelia de Lange Syndrome. In: Pagon RA, Bird TD, Dolan CR, Stephens K. GeneReviews [Internet].
  3. Oliveira et al. (2010) Hum Mutat 31(11):1216-1222.
  4. Castronovo et al. (2010) Clin Genet 78:560-564.
  5. Niu et al. (2006) Prenat Diagn 26:1054-1057.
  6. Weichert et al. (2011) J Mat Fetal Neonat Med 24(7):978-982.
  7. Deardorff et al. (2007) Am J Hum Genet 80:485-494.
  8. Bhuiyan et al. (2007) Eur J Hum Genet 15:505-508.
  9. Ratajska et al. (2010) Eur J Med Genet 53:378-382.
  10. DeScipio et al. (2005) Am J Med Gen 137A:276-282.
  11. Yan et al. (2009) J Med Genet 46:626-634.
  12. Pie et al. (2010) Am J Med Genet 152A(4):924-929.
  13. Selicorni et al. (2007) Clin Genet 72:98-108.
  14. Gillis et al. (2004) Am J Hum Genet 75:610-623.
  15. Borck et al. (2006) Hum Mutat 27:731-735.
  16. Yan et al., (2006) Am J Med Genet 140A:1531-1541
  17. Borck et al., (2004) J Med Genet 41:e128.
  18. Schoumans et al., (2007) Eur J Hum Genet 15:143-149.
  19. Gervasini et al., (2008) Clin Genet 74:531-538.
  20. Hoppman-Chaney et al., (2011) Am J Med Genet Part A 158A:193-98.

Forms and Documents

Test Details

SMC1A
  • Confirmation of a clinical diagnosis
  • Prenatal diagnosis in a family with a known mutation
  • Capillary Sequencing

Ordering

570
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)

Billing

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

References

  1. Kline et al. (1993) Am J Med Genet 47:1042-1049.
  2. Deardorff MA, Clark DM, Krantz ID. 2005 [updated 2011 Oct 27]. Cornelia de Lange Syndrome. In: Pagon RA, Bird TD, Dolan CR, Stephens K. GeneReviews [Internet].
  3. Oliveira et al. (2010) Hum Mutat 31(11):1216-1222.
  4. Castronovo et al. (2010) Clin Genet 78:560-564.
  5. Niu et al. (2006) Prenat Diagn 26:1054-1057.
  6. Weichert et al. (2011) J Mat Fetal Neonat Med 24(7):978-982.
  7. Deardorff et al. (2007) Am J Hum Genet 80:485-494.
  8. Bhuiyan et al. (2007) Eur J Hum Genet 15:505-508.
  9. Ratajska et al. (2010) Eur J Med Genet 53:378-382.
  10. DeScipio et al. (2005) Am J Med Gen 137A:276-282.
  11. Yan et al. (2009) J Med Genet 46:626-634.
  12. Pie et al. (2010) Am J Med Genet 152A(4):924-929.
  13. Selicorni et al. (2007) Clin Genet 72:98-108.
  14. Gillis et al. (2004) Am J Hum Genet 75:610-623.
  15. Borck et al. (2006) Hum Mutat 27:731-735.
  16. Yan et al., (2006) Am J Med Genet 140A:1531-1541
  17. Borck et al., (2004) J Med Genet 41:e128.
  18. Schoumans et al., (2007) Eur J Hum Genet 15:143-149.
  19. Gervasini et al., (2008) Clin Genet 74:531-538.
  20. Hoppman-Chaney et al., (2011) Am J Med Genet Part A 158A:193-98.

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
No
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.