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Noonan/LEOPARD/Cardio-Facio-Cutaneous/Costello Syndromes
Comprehensive Noonan Syndrome Resequencing Array

For prenatal diagnosis for Noonan syndrome in fetuses with abnormal ultrasound findings, see the prenatal information sheet.

The expanded gene panel now includes 11 genes
  • PTPN11
  • RAF1
  • SOS1
  • KRAS
  • BRAF
  • MAP2K1
  • MAP2K2
  • HRAS
  • NRAS
  • CBL
  • SHOC2
Noonan, LEOPARD, CFC, and Costello syndromes are autosomal dominant disorders typically caused by gain-of-function mutations in genes encoding signaling molecules of the RAS/MAPK pathway.

Noonan Syndrome: Approximately 66.5% - 79.5% of individuals with a clinical diagnosis of Noonan Syndrome are expected to have a heterozygous mutation in one of six genes, PTPN11, SOS1, RAF1, NRAS, CBL, or KRAS.

Noonan-like with loose anagen hair:The Ser2Gly mutation in the SHOC2 accounts for approximately 5% of all patients with a Noonan-like phenotype and negative results for analysis of the genes associated with Noonan syndrome. This mutation typically has a distinct clinical presentation, including features of Noonan syndrome and loose anagen hair, in association with one or more of the following features: distinctive hyperactive behavior, mitral valve dypslasia and septal cardiac defects.

LEOPARD Syndrome: Germline mutations in PTPN11 have been found in almost 90% of patients with LEOPARD syndrome. In one recent study, 2 out of 6 patients with a clinical diagnosis of LEOPARD syndrome and hypertrophic cardiomyopathy harbored a mutation in the RAF1 gene.

Cardio-Facio-Cutaneous Syndrome: In CFC, a study of 56 patients revealed an overall mutation detection rate of over 62% when BRAF, MAP2K1, MAP2K2 and KRAS were analyzed.

Costello Syndrome: 82% to 92% of patients with Costello syndrome are expected to have a missense mutation in the HRAS gene.

The expanded panel for Noonan syndrome and related disorders is offered as a low-cost and time-effective test. The expanded Noonan syndrome panel is tested using a solid-state sequencing-by-synthesis process that allows sequencing of all 11 genes in parallel. The presence of a mutation is confirmed by bi-directional dideoxy-based DNA sequencing or another appropriate method. Once a mutation in the proband is identified, mutation-specific testing in relatives and prenatal testing is available. PTPN11, SHOC2 (S2G mutation) and HRAS can also be ordered individually as separate tests (see information sheet for prices and TAT).

Information Sheet, including prices and CPT codes Back to the List
Consent Document  
Genetic Test Sample Submission Form (Test Requisition Form) including Payment Options  
Noonan, LEOPARD, Cardio-Facio-Cutaneous, Costello Syndromes Comprehensive Noonan Syndrome Resequencing Array, PTPN11, RAF1, SOS1, KRAS, BRAF, MAP2K1, MAP2K2, HRAS, NRAS, CBL, SHOC2

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