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Costello syndrome (Facio-cutaneo-skeletal syndrome; FCS syndrome)
HRAS, homolog of the V-HA-RAS harvey rat sarcoma viral oncogene
Costello (FCS) syndrome is a rare, complex developmental disorder that clinically overlaps with Noonan syndrome and Cardio-Facio-Cutaneous (CFC) syndrome. Problems during infancy include feeding difficulties, failure to thrive, and mild to moderate developmental and growth delay. Typically, the facial features are coarse with a wide forehead, epicanthal folds, thick ear lobes and lips. About 63% of patients have cardiovascular malformations, most commonly pulmonic stenosis, hypertrophic cardiomyopathy, and tachyarrhythmia. A predisposition for tumors manifests with benign skin tumors (papilloma) around the mouth, nose and anus. In 10%-15% of patients malignant tumors will develop, such as rhabdomyosarcoma, neuroblastoma, ganglioneuroblastoma, and transitional carcinoma of the bladder. Other features may include lax skin, acanthosis nigricans, musculo-skeletal abnormalities, visual impairment, gastroesophageal reflux, and endocrine abnormalities, including pubertal delay and osteoporosis. It has been shown that 82%-92% of patients with Costello syndrome have a germline mutation in the HRAS gene on chromosome 11p13.3, encoding a member of the superfamily of small GTP-binding proteins. The mutations result in a gain of function by constitutively activating downstream signaling pathways that control cell proliferation and differentiation.
In Costello syndrome, the coding exons 2-6 of the HRAS gene and flanking splice sites are analyzed by bi-directional DNA sequencing. Using this approach, our method is >99% sensitive to identify a HRAS mutation, if it exists. Analysis is performed from a peripheral blood sample in EDTA or buccal (cheek) swabs. Carrier testing of relatives and prenatal diagnosis in at-risk pregnancies is available once the mutation in a family has been defined.
Information Sheet, including prices and CPT codes
Consent Document
Genetic Test Sample Submission Form (Test Requisition Form) including Payment Options
Costello syndrome, Facio-cutaneo-skeletal syndrome, Faciocutaneoskeletal syndrome, FCS syndrome, HRAS, V-HA-RAS harvey rat sarcoma viral oncogene, failure to thrive, mental retardation, dysmorphic, cardiac, pulmonic stenosis, cardiomyopathy, tachyarrhythmia, skin tumors, papilloma, cancer, lax skin, Noonan syndrome, Cardio-Facio-Cutaneous syndrome
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