This panel consists of 23 genes associated with various RASopathy disorders. Multisystem effects of alterations in the RAS-MAPK pathway lead to physiological and anatomical abnormalities including dysmorphic features, heart defects, short stature, skin lesions, and intellectual disability. Conditions associated with mutations in the RAS-MAPK pathway include:
Cardio-facio-cutaneous syndrome - Features of CFC syndrome include macrocephaly, cardiac abnormalities, short neck, ectodermal changes, and variable degrees of intellectual disability.
Costello syndrome - This condition is characterized by intellectual disability, failure to thrive, coarse facial features, loose skin, hyperextensibility, short stature, and heart defects. Papillomatous skin lesions in the oral, nasal, and anal regions are common.
LEOPARD syndrome - This disorder, also known as multiple lentigines syndrome, involves lentigines (pigmented skin lesions), cardiac rhythm abnormalities, hypertelorism, pulmonic stenosis, growth retardation, and deafness. Intellectual disability is common.
Noonan syndrome - Features of Noonan syndrome include short stature, a broad or webbed neck, low-set nipples, heart defects, and mild intellectual disability in approximately 1/3 of patients.
Neurofibromatosis - Individuals with Neurofibromatosis 1 (NF1) have two or more of the following findings: six or more cafe au laits spots, two or more neurofibromas or one plexiform neuroma, axial or inguinal freckling, Lisch nodules, optic glioma, specific skeletal findings, or an affected first-degree relative. This condition is relatively common, and it demonstrates a wide range of expressivity, even within the same family. Neurofibromatosis 2 (NF2) is a rare disorder characterized by acoustic neuromas and vestibular schwannomas that may affect hearing and balance. New mutations are responsible for approximately half of all cases.
Schwannomatosis - This condition includes non-vestibular schwannomas that are often associated with significant degrees of pain. Scwhannomas may be widespread or limited to a specific area of the body.
Legius syndrome - The phenotype of Legius syndrome may resemble that of Neurofibromatosis 1 with the exception of cafe au laits spots. Other dysmorphic features may or may not be present. This disorder is caused by mutations in SPRED1.