Ordering Recommendation

Acceptable initial test to confirm a clinical diagnosis of Noonan syndrome or LEOPARD syndrome.

Mnemonic
NS REFLEX
Methodology

Polymerase Chain Reaction/Sequencing

Performed

Varies

Reported

28-35 days

New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 1 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable

Reference Interval
Interpretive Data

Background Information for Noonan Syndrome (PTPN11) Sequencing with Reflex to (SOS1) Sequencing:
Characteristics of NS: Short stature, developmental delay, dysmorphic facial features, congenital heart disease, broad or webbed neck, superior pectus carinatum and inferior pectus excavatum, low-set nipples, cryptorchidism, coagulation, and lymphatic disorders.
Incidence: 1 in 1,000 to 1 in 2,500.
Inheritance: Autosomal dominant.
Penetrance: Unknown.
Cause of NS: Pathogenic mutations in PTPN11, SOS1, RAF1, KRAS and other unidentified genes.
Genes tested: PTPN11 and SOS1.
Clinical Sensitivity: Approximately 70 percent.
Methodology: Bidirectional sequencing of the entire PTPN11 coding region and intron-exon boundaries. If no known pathogenic mutations are detected, bidirectional sequencing of the SOS1 coding region and intron-exon boundaries is performed.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, deep intronic mutations and large deletions/duplications will not be detected. Mutations in genes, other than PTPN11 and SOS1, will not be evaluated.

Compliance Category

Laboratory Developed Test (LDT)

Note
Hotline History
N/A
CPT Codes

81406; If reflexed, add 81406

Components
Component Test Code* Component Chart Name LOINC
2004190 NS REFLEX Specimen
2004192 Noonan Syndrome Interpretation
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • PTPN11 and SOS1 reflex assay
Noonan Syndrome (PTPN11) Sequencing with Reflex to (SOS1) Sequencing