Card kit

Invitae Cardio-Facio-Cutaneous Syndrome Panel

Test code: 04163 •

Test description

The Invitae Cardio-Facio-Cutaneous Syndrome Panel analyzes six genes that are associated with cardio-facio-cutaneous (CFC) syndrome. CFC syndrome is one of the RASopathies, which are a class of pediatric disorders associated with genes that are members of the mitogen-activated protein kinase (Ras/MAPK) pathway. This pathway is involved in a signal transduction cascade that is necessary for the proper formation of several types of tissue during embryonic and postnatal development.

CFC syndrome is characterized by failure to thrive, feeding difficulties, congenital heart defects, distinctive facial features, curly sparse hair, skin rashes, neurologic complications (e.g., hypotonia, motor delay), and developmental delay; however, the RASopathies have several overlapping phenotypic features due to their common underlying Ras/MAPK pathway dysregulation.

CFC syndrome is a multisystemic disorder whose expression is highly variable. Proper management by specialists across a variety of disciplines is critical because CFC syndrome must be correctly identified and comprehensively managed. Distinguishing CFC syndrome from other phenotypically similar syndromes, such as Noonan syndrome or Costello syndrome, is important for proper medical management.

Disorders tested

  • cardio-facio-cutaneous syndrome (CFC)

Ordering information

Turnaround time:

10–21 calendar days (14 days on average)

New York approved:

Yes

Preferred specimen:

3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)

Alternate specimens:

Saliva, buccal swab, and gDNA are also accepted.Learn more about specimen requirementsRequest a specimen collection kit

Clinical description and sensitivity

Clinical description:

Cardio-facio-cutaneous (CFC) syndrome is a multi-system pediatric developmental syndrome that most commonly affects the heart, face, and skin. It is a member of a class of pediatric disorders called the RASopathies. CFC is a phenotypically variable disorder; not all affected individuals will present with every finding. Further, some findings may be evident at birth while others may present later.

The most commonly observed cardiac anomalies are pulmonic stenosis and other valvular defects, septal defects, hypertrophic cardiomyopathy, and arrhythmia.

Classic facial dysmorphology comprises macrocephaly, broad forehead, bitemporal narrowing, hypoplasia of the supraorbital ridges, downslanting palpebral fissures, ptosis, short nose with depressed nasal bridge and anteverted nares, high-arched palate, and low-set, posteriorly rotated ears.

Cutaneous findings usually include sparse, curly hair with sparse eyebrows and lashes, hyperkeratosis, keratosis pilaris, hemangioma, ichthyosis, progressively forming nevi, and flat, broad nails.

Other anomalies are also frequently observed, such as short stature, pectus deformity, kyphosis/scoliosis, and ocular abnormalities (strabismus, nystagmus, myopia,hyperopia, and astigmatism). Failure to thrive during infancy is typical, as are gastrointestinal complications such as reflux, vomiting, oral aversion, and constipation. Neurologic complications are observed in all patients to varying degrees and include hypotonia, hydrocephalus, motor delay, seizures, speech delay, and mild-to-severe developmental delay (there are a few individuals with IQs in the normal range). CFC syndrome is not associated with the increased risk of malignancy that has been observed in such phenotypically similar syndromes as Noonan and Costello, but some malignancies have been reported.

Clinical description and sensitivity

Clinical description:

Cardio-facio-cutaneous (CFC) syndrome is a multi-system pediatric developmental syndrome that most commonly affects the heart, face, and skin. It is a member of a class of pediatric disorders called the RASopathies. CFC is a phenotypically variable disorder; not all affected individuals will present with every finding. Further, some findings may be evident at birth while others may present later.

The most commonly observed cardiac anomalies are pulmonic stenosis and other valvular defects, septal defects, hypertrophic cardiomyopathy, and arrhythmia.

Classic facial dysmorphology comprises macrocephaly, broad forehead, bitemporal narrowing, hypoplasia of the supraorbital ridges, downslanting palpebral fissures, ptosis, short nose with depressed nasal bridge and anteverted nares, high-arched palate, and low-set, posteriorly rotated ears.

Cutaneous findings usually include sparse, curly hair with sparse eyebrows and lashes, hyperkeratosis, keratosis pilaris, hemangioma, ichthyosis, progressively forming nevi, and flat, broad nails.

Other anomalies are also frequently observed, such as short stature, pectus deformity, kyphosis/scoliosis, and ocular abnormalities (strabismus, nystagmus, myopia,hyperopia, and astigmatism). Failure to thrive during infancy is typical, as are gastrointestinal complications such as reflux, vomiting, oral aversion, and constipation. Neurologic complications are observed in all patients to varying degrees and include hypotonia, hydrocephalus, motor delay, seizures, speech delay, and mild-to-severe developmental delay (there are a few individuals with IQs in the normal range). CFC syndrome is not associated with the increased risk of malignancy that has been observed in such phenotypically similar syndromes as Noonan and Costello, but some malignancies have been reported.


Clinical sensitivity:


BRAF mutations are the most common and account for an estimated 75% of individuals with CFC syndrome. Mutations in MAP2K1 and MAP2K2 have been reported in nearly 25% of individuals with a clinical diagnosis of CFC syndrome. KRAS mutations have been observed in less than 5% of CFC syndrome individuals. Individuals with pathogenic variants in SHOC2 and SOS1 have been reported with clinical manifestations that overlap with typical Noonan or CFC syndrome features . The Invitae Cardio-Facio-Cutaneous Syndrome panel will identify mutations in nearly 100% of individuals with a clinical diagnosis of CFC syndrome.

Assay information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Assay information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

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Primary panel

6 genes selected
BRAF
KRAS
MAP2K1
MAP2K2
SHOC2
SOS1

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