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Noonan/LEOPARD/Cardio-Facio-Cutaneous/Costello Syndromes
Comprehensive Noonan Syndrome Resequencing Array
PTPN11
RAF1
SOS1
KRAS
BRAF
MAP2K1
MAP2K2
HRAS
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 65% - 78% of individuals with a clinical diagnosis of Noonan Syndrome are expected to have a heterozygous mutation in one of four genes, PTPN11, SOS1, RAF1 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 PTPN11, SOS1, RAF1, and KRAS genes. 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 RAF1Gene.
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.
Testing for Noonan syndrome and related disorders is now offered as a
low-cost and time-effective
test. The custom-designed resequencing array includes 8 genes of the RAS/MAPK pathway, which are sequenced simultaneously. Testing also includes mutation specific analysis for the Ser2Gly SHOC2 gene mutation using by bi-directional dideoxy-based DNA sequencing. 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.
ANY
of these genes can also be ordered individually as a separate test. (see information sheet for prices and TAT)
ATTENTION
: For any person who had testing for any of these disorders, which was started before July 7, 2009 and who has already incurred $1,500 or more in expenses, analysis of the remaining genes present as a part of the resequencing panel is available for $500.
Information Sheet, including prices and CPT codes
Consent Document
Genetic Test Sample Submission Form (Test Requisition Form) including Payment Options
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