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 Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

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