Definition
Neurofibromatosis type 1 is a relatively common tumor predisposition syndrome that is clinically evident through café au lait spots, neurofibromas on and under the skin, and freckles in the armpits and the groin area. In addition, NF1 is characterized by iris hamartomas, characteristic bone changes, scoliosis, macrocephaly, dwarfism, and learning disabilities. Occasionally, tumors may also develop in the vicinity of cranial nerves or the spinal cord and, in principle, around every peripheral nerve. NF1 is normally diagnosed during childhood.
Key Data
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Synonyms | NF1, Recklinghausen’s disease |
Gene | NF1 tumor suppressor gene |
Gene product | Neurofibromin |
Function | The regulation of cell growth and cell differentiation in nerve cells and myelin sheaths. Tumors develop due to the down-regulation of the RAS signal transduction cascade. |
Heredity | Autosomal dominant (50%), de novo (50% ; intron mutation, exon deletion, missense mutation, insertion, point mutation, stop mutations), rarely mosaicism or a segmentally limited postzygotic form of NF1 |
Prevalence | 1:3.000 |
Genotype-phenotype correlation | Low, with very high expression variability |
Penetrance | Nearly 100% in adulthood |
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Diagnosis
Diagnostic Criteria
≥ 2 of the following criteria must be present; please note: age-dependent development!
Differential Diagnoses
Clinical Presentation
In the vast majority of cases, the diagnosis of “NF1” can be made clinically on the basis of the classic diagnostic criteria. Other common but not pathognomonic findings include the following:
Predisposition to Cancer
With familial NF1, an early clinical diagnosis is often possible (during infancy / early childhood). Discreet progressions are also found with de novo mutations or mosaic mutations, sometimes not becoming symptomatic until school age or early adulthood.