Prenatal Noonan Syndrome

Prenatal diagnosis for at-risk pregnancies when a parent is affected or when abnormalities are seen on fetal ultrasound. Noonan syndrome and Noonan-like syndromes tend to be predominantly associated with different genes or different variants within the same genes. Clinical overlap of the various syndromes is explained by the fact that all of these genes code for components of the same intracellular signaling pathway, namely the Ras/MAPK signaling cascade.

Genetic testing for Noonan syndrome and related disorders may:

• Establish or confirm a clinical diagnosis of Noonan syndrome, LEOPARD syndrome, Costello syndrome, or cardiofaciocutaneous syndrome.

• Identify previously undiagnosed parents, siblings, and other relatives of patients with Noonan syndrome or LEOPARD syndrome.

• Facilitate appropriate genetic counseling for family members.

Please call CMBP genetic coordinators at 800-345-4363 prior to submitting a fetal sample. Test orders must include attestation that the provider has the patient's informed consent for genetic testing. See sample physician office consent form: Consent for Genetic Testing. In the case of a family test (ie, known mutation), family tests will only be accepted from family members of index cases tested at LabCorp. Please order test 451385 to submit family testing for Noonan syndrome.

This analysis does not rule out: germline mosaicism, the presence of large chromosomal aberrations including deletions, insertions, and rearrangements, mutations in regions or genes not included in this test, and possible inter/intragenic interactions between sequence variants. False positives or negative results may occur for reasons that include: genetic variants, blood transfusions, bone marrow transplantation, mislabeled specimens or erroneous representation of family relationships.

Mutation analysis is performed using the AgilentSure Select XT® enrichment method and the Illumina® next-generation sequencing platform. Regions of interest include all exons and splice junctions for each gene and limited regions for the following: APOB (556bp of exon 26) and MED12 (c.3020A>G). Sequencing reads are aligned with the hg19 build of the human genome reference sequence. Analytical sensitivity is based on the depth of coverage across the regions of interest and is provided separately for each gene. Greater than 98% of target bases are synonymous variants not previously recorded at greater than or equal to 20x coverage. Sanger sequencing is used to confirm mutation identity and analyze regions with low coverage. Variants are reported using numbering and nomenclature recommended by the Human Genome Variation Society (HGVS). Variants known to be benign and synonymous variants not previously recorded in our internal variant databases are not reported.