Cardio-Facio-Cutaneous Syndrome via the MAP2K1 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 8195 | MAP2K1 | 81406 | 81406,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Clinical Features
Cardio-facio-cutaneous syndrome (CFCS, OMIM 115150) is a rare developmental disorder characterized by distinctive facial appearance, congenital cardiac and ectodermal abnormalities, postnatal growth failure, feeding difficulties with failure to thrive, and neurological findings. Facial features include high forehead; short, upturned nose with a low nasal bridge; prominent external ears that are posteriorly angulated; and ocular hypertelorism. The most common cardiac abnormalities include pulmonic stenosis and atrial septal defects. Ectodermal abnormalities are heterogeneous in features and severity. They include café au lait spots, erythema, keratosis, ichthyosis, eczema, sparse and brittle hair, and nail dystrophy. The neurological findings include seizures, hypotonia, macrocephaly and various degrees of mental and cognitive delay (Reynolds et al. Am J Med Genet 25:413-427, 1986).
Genetics
CFCS is caused by variants in four genes within the RAS/MAPK pathway: BRAF, MAP2K1, MAP2K2, and KRAS (Rodriguez-Viciana et al. Science 311:1287-1290, 2006; Niihori et al. Nat Genet 38:294-296, 2006). To date, ten MAP2K1germline variants, including nine missense variants and one small in-frame deletion, have been reported in patients with CFCS. MAP2K1 variants account for ~ 10% of all cases genotyped (Schulz et al. Clin Genet 73:62-70, 2008). Although most variants reported to date were found in exons 2 and 3, recently one CFCS-causative variant was found in exon 6. All CFCS patients with MAP2K1 variants are sporadic resulting from de novo dominant variants. To date, no mosaicism in the MAP2K1gene has been reported in CFCS patients (Rauen, GeneReviews, 2010). Somatic recurrent MAP2K1 variants have been implicated in several human cancers including melanoma (Nikolaev et al. Nat Genet 44:133-139, 2011). The MAP2K1 gene encodes the MEK1 protein, a member of the RAS/MAPK pathway that is involved in the control of cell proliferation, migration, division and differentiation.
Clinical Sensitivity - Sequencing with CNV PG-Select
This test will detect causative MAP2K1 variants in ~ 10% of CFCS patients (Schulz, Clin Genet 73:62-70, 2008).
Testing Strategy
This test provides full coverage of all coding exons of the MAP2K1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Patients with a clinical diagnosis of CFCS who do not have variants in BRAF are candidates for this test. As the clinical features of Noonan syndrome and Costello syndrome overlap with CFCS, patients who test negative for variants in the genes most commonly associated with those conditions are also candidates.
Patients with a clinical diagnosis of CFCS who do not have variants in BRAF are candidates for this test. As the clinical features of Noonan syndrome and Costello syndrome overlap with CFCS, patients who test negative for variants in the genes most commonly associated with those conditions are also candidates.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| MAP2K1 | 176872 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Cardiofaciocutaneous syndrome 3 | 615279 |
Related Test
| Name |
|---|
| Comprehensive Cardiology Panel |
Citations
- Niihori T, Aoki Y, Narumi Y, Neri G, Cavé H, Verloes A, Okamoto N, Hennekam RCM, Gillessen-Kaesbach G, Wieczorek D, Kavamura MI, Kurosawa K, Ohashi H, Wilson L, Heron D, Bonneau D, Corona G, Kaname T, Naritomi K, Baumann C, Matsumoto N, Kato K, Kure S, Matsubara Y. 2006. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat. Genet. 38: 294–296. PubMed ID: 16474404
- Nikolaev SI, Rimoldi D, Iseli C, Valsesia A, Robyr D, Gehrig C, Harshman K, Guipponi M, Bukach O, Zoete V, Michielin O, Muehlethaler K, Speiser D, Beckmann JS, Xenarios I, Halazonetis TD, Jongeneel CV, Stevenson BJ, Antonarakis SE. 2011. Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma. Nature Genetics 44: 133–139. PubMed ID: 22197931
- Rauen KA. 2010. Cardiofaciocutaneous Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301365
- Reynolds JF, Neri G, Herrmann JP, Blumberg B, Coldwell JG, Miles PV, Opitz JM. 1986. New multiple congenital anomalies/mental retardation syndrome with cardio-facio-cutaneous involvement--the CFC syndrome. Am. J. Med. Genet. 25: 413–427. PubMed ID: 3789005
- Rodriguez-Viciana P, Tetsu O, Tidyman WE, Estep AL, Conger BA, Cruz MS, McCormick F, Rauen KA.. 2006. Germline Mutations in Genes Within the MAPK Pathway Cause Cardio-facio-cutaneous Syndrome. Science 311: 1287–1290. PubMed ID: 16439621
- Schulz, A. L., et.al. (2008). "Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome." Clin Genet 73(1): 62-70. PubMed ID: 18042262
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
Requisition Form
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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ORDER OPTIONS
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