Neurofibromatosis type 1 (NF1). von Recklinghausen neurofibromatosis.
Incidence
It is a common autosomal dominant disorder affecting 1 in 3000 individuals. There is a high spontaneous mutation rate in NF1, with 30 to 50 percent of cases representing new mutations.
Clinical Characteristics
von Recklinghausen neurofibromatosis, or neurofibromatosis type 1 (NF1). This condition is considered a neurocutaneous syndrome or phakomatosis. NF1 is caused by defects in a gene mapping to chromosome 17, whose product (neurofibromin) is presumed to be involved in modulating a signal transduction pathway. It is characterized clinically by the finding of two or more of the following: cafe café au lait spots, neurofibromas, freckling in non-sun-exposed areas, optic glioma, Lisch nodules, distinctive bony lesions, or a first-degree relative with NF1. Less common manifestations of NF1 include short stature and macrocephaly. Patients can also have learning disabilities, seizures, scoliosis, hypertension, plexiform neurofibromas, or pheochromocytomas. Although the penetrance of NF1 is essentially 100 percent, NF1 tends to show variable expressivity, in that there is a wide range of clinical severity and complications in patients within the same family, who all presumably carry the same mutation.
Treatment of patients with NF1 is directed at education and genetic counseling issues, early detection of malignancy, and surveillance for the appearance of complications of NF1. Approximately one-third of patients with NF1 will suffer from one or more of these serious complications during their lifetime: Learning Disability, Plexiform Neurofibromas, Malignancy, Seizures, Scoliosis, Pseudarthrosis, Hypertension.
Genetics of NF1: Approximately 50 percent of children of individuals affected with NF1 were also afflicted, regardless of sex. However 30 to 50 percent of patients with NF1 do not have an affected parent. Such individuals presumably represent spontaneous mutations. Neurofibromatosis 1 remains a clinical diagnosis.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
Neurofibromatosis 1 remains a clinical diagnosis.The diagnosis of neurofibromatosis is largely based on clinical criteria despite progress in defining the molecular genetics of the disorder. Diagnostic Criteria for NF1: Two or more of the following: A) Six or more cafe café au lait spots, 1.5 cm or larger in postpubertal individuals, 0.5 cm or larger in prepubertal individuals. Two or more neurofibromas of any type or B) One or more plexiform neurofibromas, Freckling of armpits or groin, Optic glioma (tumor of the optic pathway), Two or more Lisch nodules (benign iris hamartomas). A distinctive bony lesion such as Dysplasia of the sphenoid bone or Dysplasia or thinning of long bone cortex and finally First-degree relative with NF1.