Noonan Syndrome

Test name:  Noonan Syndrome (NS) Testing (PTPN11, SOS1, RAF1, KRAS)
Also known as: Noonan Syndrome Tiered Gene Sequencing Panel, Gene Sequencing for individual genes (PTPN11, SOS1, RAF1, KRAS), Deletion/Duplication for PTPN11

Indications:

  • Clinical features of Noonan Syndrome diagnosis including:
    • short stature
    • congenital heart defects
    • broad or webbed neck
    • unusual chest shape (pectus carinatum or pectus excavatum)
    • low-set nipples
    • cryptorchidism in males
    • coagulation defects
    • characteristic facial features
    • developmental delay/intellectual delay, variable degree
  • Postnatal testing for at risk relative of previously identified familial mutation in PTPN11, SOS1, RAF1, or KRAS or deletion/duplication

Test Information:

Name of Test Method Additional Information

 

Tiered
Noonan Syndrome Panel

 Gene sequencing of exons noted
  • Tier 1: PTPN11 exons 2, 3, 4, 7, 8 &13, if negative Tier 2
  • Tier 2: PTPN11 remaining exons, if negative Tier 3
  • Tier 3: RAF1 exons 7, 14, & 17 + SOS1 exons 7, 8, 11 & 17, if negative Tier 4
  • Tier 4: KRAS exons 2-6 + SOS1 remaining 20 exons
  
  • Tiered gene sequencing is the most cost effective testing rather than ordering all gene sequencing tests to run concurrently
  • Deletions/duplications are not detected with this panel
PTPN11 (12q24.13) gene sequencing
  • Accounts for approximately 50% of individuals with NS
  • Pulmonic stenosis frequent
  • Sequence analysis detects mutations >90%
  • Rare partial or whole gene deletions/duplications not detected with this method
RAF1 (3p25) gene sequencing
  • Accounts for approximately 3-17% of individuals with NS
  • Hypertrophic cardiomyopathy seen in ~95% with mutation
  • Sequence analysis detects >99% of mutations in RAF1
SOS1 (2p22-p21) gene sequencing
  • Accounts for approximately 13% of individuals with NS
  • More often seen with ectodermal anomalies and cardiac septal defects
KRAS (12p12.1) gene sequencing
  • Accounts for <5% of NS
  • Often higher chance of MR
Deletion/duplication
testing of PTPN11		 Microarray – see 180K Microarray for details
  • Two duplications involving PTPN11have been noted but detection unknown
  • Currently no deletion or duplication has been seen for NS in RAF1, SOS1, or KRAS
Familial Mutation Analysis Available on PTPN11, RAF1, SOS1, or KRAS if mutation previously identified in family member*
  • Postnatal only
  • *If sequencing was not previously completed at our laboratory call to inquire if testing is appropriate at HGL

 

 Additional tests available on postnatal samples (refer to additional pages for details):
     Postnatal Chromosome Analysis
     Postnatal FISH including Aneuploidy FISH and Constitutional FISH
     180K Microarray
     UPD Array
     Single gene testing – refer to Test Catalog for tests offered at HGL
     Coming soon: Next Generation Sequencing Panel for Noonan Syndrome

Specimen requirements:

Sequencing only (tiered panel or individual genes):

  • Adult: one 3-5 ml whole blood EDTA (purple top) tube
  • Newborn: one 3-5 ml whole blood EDTA (purple top) tube (minimum 1 ml)

Array with or without sequencing:

  • Adult: one 3-5 ml whole blood sodium heparin (green top) tube
  • Newborn: one 3-5 ml whole blood sodium heparin (green top) tube (minimum 1 ml)

CPT codes:

  • Tiered Noonan Syndrome Panel:
    • Tier 1: 83894, 83896(x6), 83898(x6), 83904(x6)*
    • Tier 2: 83894, 83896(x9), 83898(x9), 83904(x9)
    • Tier 3: 83894, 83896(x6), 83898(x6), 83904(x6)
    • Tier 4: 83894, 83896(x25), 83898(x25), 83904(x25)
    • PTPN11 sequencing: 83894(x2), 83896(x15), 83898(x21), 83904(x24)
    • RAF1 sequencing: 83896(x10), 83898(x3), 83904(x20)
    • SOS1 sequencing: 83894(x2), 83896(x28), 83898(x28), 83904(x28)
    • KRAS sequencing: 83896(x5), 83898(x6), 83904(x8)
    • Deletion/duplication testing of PTPN11: Refer to 180K Microarray for details
    • Familial Mutation Analysis: Contact the laboratory billing staff for current CPT codes

*Unless using stored DNA from a prior sample, the following DNA Extraction codes (83891, 83894, 83907, 84311) will also apply once for molecular testing.

Pricing: Contact the laboratory billing staff for current costs

Shipping & Handling

Required forms: Postnatal Test Request Form

Turn-around time:

  • Tiered Noonan Syndrome Panel: 7 weeks (depends on # of tiers completed)
  • PTPN11sequencing: 4 weeks
  • RAF1sequencing: 4 weeks
  • SOS1sequencing: 4 weeks
  • Deletion/duplication testing of PTPN11: 1-2 weeks
  • Familial Mutation Analysis: 2 weeks

References:  GeneReviews

revised: 8-16-12

contact us

Phone:  402-559-5070 
               Option 3
800-656-3937 x95070
Fax:  402-559-7248

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