Overview of diagnosis
Diagnosis of neurofibromatosis type 1 (NF1) is based on clinical characteristics, using criteria established by the National Institutes of Health1. Molecular genetic testing is rarely necessary to diagnose neurofibromatosis type 1 because the diagnostic criteria are sensitive and specific.
The main disease manifestations that inform a diagnosis of neurofibromatosis type 1 include cafe-au-lait macules, axillary freckling, neurofibromas and Lisch nodules. In people older than 5 years, if all the main disease manifestations are absent on screening, a diagnosis of neurofibromatosis type 1 can be excluded with more than 95% certainty; the level of certainty is higher for adults.
The clinical diagnostic criteria are important because several other rare conditions are associated with multiple cafe-au-lait macules, and 3 or fewer cafe-au-lait macules are normal in the populationMiller, 2019.
Sometimes people have features of neurofibromatosis type 1 in only one part of the body. This is called segmental neurofibromatosis. It is probably due to mosaicism for an NF1 gene mutation in a subset of cells or tissues.
Clinical diagnostic criteria for neurofibromatosis type 1 are also used to exclude or establish the diagnosis in parents of affected children, and enable genetic counselling about the risk of neurofibromatosis type 1 recurring in a family.