Clinical and genetic aspects of neurofibromatosis 1

Neurofibromatosis I is an autosomal dominant disorder characterized by multiple cafe-au-lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, and iris Lisch nodules. Learning disabilities are present in at least 50% of individuals with neurofibromatosis 1. Less common but potentially more serious manifestations include plexiform neurofibromas, optic nerve and other central nervous system gliomas, malignant peripheral nerve sheath tumors, scoliosis, tibial dysplasia, and vasculopathy. The diagnosis of neurofibromatosis 1 is usually based on clinical findings. Neurofibromatosis I, one of the most common Mendelian disorders, is caused by heterozygous mutations of the NF1 gene. Almost one half of all affected individuals have de novo mutations. Molecular genetic testing is available clinically but is infrequently needed for diagnosis. Disease management includes referral to specialists for treatment of complications involving the eye, central or peripheral nervous system, cardiovascular system, spine, or long bones. Surgery to remove both benign and malignant tumors or to correct skeletal manifestations is sometimes warranted. Annual physical examination by a physician familiar with the disorder is recommended. Other recommendations include ophthalmologic examinations annually in children and less frequently in adults, regular developmental assessment in children, regular blood pressure monitoring, and magnetic resonance imaging for follow-up of clinically suspected intracranial and other internal tumors. Genet Med 2010:12(1):1-11.