Cardiofaciocutaneous syndrome (CFC) is a disorder that affects many parts of the body, particularly the heart (cardio-), facial features (facio-), and the skin and hair (cutaneous). People with this condition also have delayed development and intellectual disability, usually ranging from moderate to severe. CFC is considered to be an autosomal dominant condition, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Cardiofaciocutaneous syndrome usually results from new gene mutations and occurs in people with no history of the disorder in their family. In a few reported cases, an affected person has inherited the condition from an affected parent.
Heart defects occur in most people with cardiofaciocutaneous syndrome. The heart problems most commonly associated with this condition is pulmonary stenosis, atrial septal defect, and hypertrophic cardiomyopathy. CFC is also characterized by distinctive facial features. These include a high forehead that narrows at the temples, a short nose, widely spaced eyes, outside corners of the eyes that point downward, droopy eyelids, a small chin, and low-set ears. Overall, the face is broad and long, and the facial features are sometimes described as "coarse."
Skin abnormalities occur in almost everyone with CFC. Many affected people have dry, rough skin; dark-colored moles; wrinkled palms and soles; and a skin condition called keratosis pilaris, which causes small bumps to form on the arms, legs, and face. People with cardiofaciocutaneous syndrome also tend to have thin, dry, curly hair and sparse or absent eyelashes and eyebrows.
Infants with cardiofaciocutaneous syndrome typically have hypotonia, feeding difficulties, and a failure to grow and gain weight at the normal rate. Additional features of this disorder in children and adults can include an unusually large head, short stature, problems with vision, and seizures.
The signs and symptoms of cardiofaciocutaneous syndrome overlap significantly with those of two other genetic conditions, Costello syndrome and Noonan syndrome. The three conditions are distinguished by their genetic cause and specific patterns of signs and symptoms; however, it can be difficult to tell these conditions apart, particularly in infancy. Unlike Costello syndrome, which significantly increases a person's cancer risk, cancer does not appear to be a major feature of cardiofaciocutaneous syndrome.
The BRAF, MAP2K1, MAP2K2, and KRAS genes provide instructions for making proteins that work together to transmit chemical signals from outside the cell to the cell's nucleus. This chemical signaling pathway, known as the RAS/MAPK pathway, is essential for normal development before birth. It helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions, cell movement, and the self-destruction of cells. The SHOC2 gene encodes a protein that consists almost entirely of leucine-rich repeats, a domain implicated in protein-protein interactions. The protein may function as a scaffold linking RAS to downstream signal transducers in the RAS/ERK MAP kinase signaling cascade. Mutations in this gene have been associated with Noonan-like syndrome with loose anagen hair. We provide testing for the mutations below that are believed to cause CFC and related disorders.
||Mutations in the BRAF gene are most common, accounting for 75 to 80 percent of all cases.
Fewer than 5 percent of cases are caused by mutations in the KRAS gene.
||10 to 15 percent of cases result from mutations in MAP2K1.
||10 to 15 percent of cases result from mutations in MAP2K2.
|Noonan like syndrome with loose anagen hair
||Clinical manifestations in SHOC2 positive mutation patients overlaps with those in patients with CFC or Noonan syndrome, but the loose anagen hair is distinctive to SHOC2 mutation-positive patients.
Methodology: Sequencing of entire coding region for each gene
Purpose:Confirmation of Clinical Diagnosis
Test Requisition: Sequencing Requisition
BRAF CPT Code: 81406 Cost: $1089.00
KRAS CPT Code: 81405 Cost: $528.00
MAP2K1 CPT Code: 81406 Cost: $1100.00
MAP2K2 CPT Code: 81406 Cost: $1100.00
SHOC2 CPT Code: 81405 Cost: $440.00
Panel CPT Codes: 81405x2, 81406x3 Cost: $4257.00
Turn-around-time: 5-6 weeks each test
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