Legius Syndrome

Neurofibromatosis 1-like syndrome, or Legius syndrome, is an autosomal dominant disorder resembling neurofibromatosis 1 with cafe-au-lait spots, axillary freckling, macrocephaly, learning disabilities, ADHD, developmental delays, and dysmorphic facial features similar to Noonan syndrome (Denayer et al., 2010; Brems et al., 2007). Other typical NF1 features such as Lisch nodules of the iris, neurofibromas and central nervous system tumors are systematically absent (Denayer et al., 2010). Two studies revealed that approximately 2% of individuals fulfilling diagnostic criteria for NF1 have SPRED1 mutations (Messiaen et al 2009, Muram-Zborovski et al 2010).

Tests Available

Forms and Documents

Test Details

NF1, NF2, SMARCB1, SPRED1
  • Establish or confirm a clinical diagnosis
  • Identification of at-risk family members
  • Development of an appropriate evaluation and management Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Deletion/Duplication Analysis
  • MLPA
  • Next-Gen Sequencing

Ordering

961
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81405x2, 81406x1, 81408x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Friedman JM. Neurofibromatosis 1. 1998 Oct 2 [Updated 2014 Sep 4]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1
  2. Evans DG. Neurofibromatosis 2. 1998 Oct 14 [Updated 2011 Aug 18]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK12
  3. Stevenson D, Viskochil D, Mao R, et al. Legius Syndrome. 2010 Oct 14 [Updated 2015 Jan 15]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. Available from: http://www.nc
  4. Trovo-Marqui, A, Tajara E. (2006) Clin. Genet. 70: 1-13 (PMID: 16813595)
  5. Curto M, McClatchey A. (2008) Brit. J. Cancer 98: 256-262 (PMID: 17971776)
  6. Brems et al., (2012) Hum. Mutat. 33: 1538-1546 (PMID: 22753041)
  7. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 609291: 09/24/13: World Wide Web URL: http://omim.org/.
  8. Spencer et al., (2011) Am J Med Genet Part A 155:1352–1359 (PMID: 21548021)
  9. Evans D. (2009) Genet Med 11: 599–610 (PMID: 19652604)
  10. Ahronowitz et al., (2007) Hum. Mutat. 28: 1-12 (PMID: 16983642)
  11. Wimmer et al., (2006) Genes Chromosomes Cancer 45:265–76 (PMID: 16283621)
  12. Valero et al. (2011) J Mol Diagn 13:113–22 (PMID: 21354044)
  13. Sabbagh et al., (2013) Hum. Mutat. 34:1510-1518 (PMID: 23913538)
  14. Baser et al., (2006) Hum Mutat. 27: 297-306 (PMID: 16521120)
  15. Stumpf et al. (1988) Arch Neurol 45:575-578 (PMID: 3128965)
  16. Messiaen et al., (2009) JAMA 302:2111–8 (PMID: 19920235)
  17. Pasmant et al., (2010) Hum Mutat 31:E1506–18 (PMID: 20513137)
  18. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 611413: 02/20/13: World Wide Web URL: http://omim.org/.
  19. Muram-Zborovski et al, (2010) J Chil Neurol 25(10): 1203-1209 (PMID: 20179001)
  20. Hadfield et al., (2008) J Med Genet 45:332-339 (PMID: 18285426)
  21. Plotkin et al. (2013) Am J Med Genet A 161A(3): 405-16 (PMID: 23401320)
  22. Van den Munckhof et al., (2012) Neurogenetics 13(1): 1-7 (PMID: 22038540)
  23. Bacci et al., (2010) Neurogenetics 11(1) 73-80 (PMID: 19582488)
  24. MacCollin et al., (2005) Neurology 64: 1838-1845 (PMID: 15955931)
  25. Ullrich N (2015) J of Child Neurology pii: 0883073815604220 (PMID: 26459515)
  26. MacCollin et al., (2003) Neurology 60: 1968-74 (PMID: 12821741)
  27. Slattery et al., (2015) Otolaryngol Clin North Am 48(3): 443-60 (PMID: 26043141)
  28. Smith et al., (2015) Hum Mut 37: 250-256 (PMID: 26615784)
  29. Colley et al., (1996) Clin Genet 49: 59-64 (PMID: 8740913)

Forms and Documents

Test Details

NF1, SPRED1
  • Establish or confirm a clinical diagnosis
  • Identification of at-risk family members
  • Development of an appropriate evaluation and management Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Deletion/Duplication Analysis
  • MLPA
  • Next-Gen Sequencing

Ordering

962
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81405x1, 81408x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Friedman JM. Neurofibromatosis 1. 1998 Oct 2 [Updated 2014 Sep 4]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1
  2. Evans DG. Neurofibromatosis 2. 1998 Oct 14 [Updated 2011 Aug 18]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK12
  3. Stevenson D, Viskochil D, Mao R, et al. Legius Syndrome. 2010 Oct 14 [Updated 2015 Jan 15]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. Available from: http://www.nc
  4. Trovo-Marqui, A, Tajara E. (2006) Clin. Genet. 70: 1-13 (PMID: 16813595)
  5. Curto M, McClatchey A. (2008) Brit. J. Cancer 98: 256-262 (PMID: 17971776)
  6. Brems et al., (2012) Hum. Mutat. 33: 1538-1546 (PMID: 22753041)
  7. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 609291: 09/24/13: World Wide Web URL: http://omim.org/.
  8. Spencer et al., (2011) Am J Med Genet Part A 155:1352–1359 (PMID: 21548021)
  9. Evans D. (2009) Genet Med 11: 599–610 (PMID: 19652604)
  10. Ahronowitz et al., (2007) Hum. Mutat. 28: 1-12 (PMID: 16983642)
  11. Wimmer et al., (2006) Genes Chromosomes Cancer 45:265–76 (PMID: 16283621)
  12. Valero et al. (2011) J Mol Diagn 13:113–22 (PMID: 21354044)
  13. Sabbagh et al., (2013) Hum. Mutat. 34:1510-1518 (PMID: 23913538)
  14. Baser et al., (2006) Hum Mutat. 27: 297-306 (PMID: 16521120)
  15. Stumpf et al. (1988) Arch Neurol 45:575-578 (PMID: 3128965)
  16. Messiaen et al., (2009) JAMA 302:2111–8 (PMID: 19920235)
  17. Pasmant et al., (2010) Hum Mutat 31:E1506–18 (PMID: 20513137)
  18. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 611413: 02/20/13: World Wide Web URL: http://omim.org/.
  19. Muram-Zborovski et al, (2010) J Chil Neurol 25(10): 1203-1209 (PMID: 20179001)
  20. Hadfield et al., (2008) J Med Genet 45:332-339 (PMID: 18285426)
  21. Plotkin et al. (2013) Am J Med Genet A 161A(3): 405-16 (PMID: 23401320)
  22. Van den Munckhof et al., (2012) Neurogenetics 13(1): 1-7 (PMID: 22038540)
  23. Bacci et al., (2010) Neurogenetics 11(1) 73-80 (PMID: 19582488)
  24. MacCollin et al., (2005) Neurology 64: 1838-1845 (PMID: 15955931)
  25. Ullrich N (2015) J of Child Neurology pii: 0883073815604220 (PMID: 26459515)
  26. MacCollin et al., (2003) Neurology 60: 1968-74 (PMID: 12821741)
  27. Slattery et al., (2015) Otolaryngol Clin North Am 48(3): 443-60 (PMID: 26043141)
  28. Smith et al., (2015) Hum Mut 37: 250-256 (PMID: 26615784)
  29. Colley et al., (1996) Clin Genet 49: 59-64 (PMID: 8740913)

Forms and Documents

Test Details

A2ML1, ACTB, ACTG1, BRAF, CBL, HRAS, KAT6B, KRAS, LZTR1, MAP2K1, MAP2K2, NF1, NRAS, NSUN2, PPP1CB, PTPN11, RAF1, RASA1, RASA2, RIT1, RRAS, SHOC2, SOS1, SOS2, SPRED1
  • Diagnosis in a patient based on clinical diagnosis
  • Diagnosis for known familial pathogenic variant(s)
  • Distinguish between causes and forms of RASopathies and disorders with phenotypically similar clinical presentations
  • Genetic counseling, especially regarding recurrence risk
  • Next-Gen Sequencing
  • Deletion/Duplication Analysis

Ordering

TA06
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs | Extracted DNA

Billing

81442x1
Yes
Yes
* For price inquiries please email zebras@genedx.com