| Note | NF1 is an hamartoneoplastic syndrome; hamartomas are localized tissue proliferations with faulty differenciation and mixture of component tissues; they are heritable malformations that have a potential towards neoplasia; the embryonic origin of dysgenetic tissues involved in NF1 is ectoblastic. |
| Phenotype and clinics | Diagnosis is made on the ground of at least 2 of the following: café-au-lait spots (6 or more over 0. 5 cm of diameter (in pre-puberty)) 2 or more neurofibromas or 1 plexiform neurofibromas (mainly cutaneous) 2 or more Lisch nodules (melanocytic hamartomas of the iris) freckling in the axillary/inguinal region (Crowe's sign) glioma of the optic nerve distintive bone anomalies (scoliosis, pseudoarthroses, bony defects (orbital wall) ...) positive family history Other features: macrocephaly epilepsy mental retardation in 10 %; learning diabilities in half patients sexual precocity and other endocrine anomalies hypertension (renal artery stenosis) |
| Neoplastic risk | 5% of NF1 patients experience a malignant neoplasm neurofibromas, especially the plexiform variety; polyclonal (benign) proliferation; may be present at birth or appear later, may be a few or thousands, small or enormous, occur in the skin and in various tissus and organs; neurofibromas localized to the spine are extremely difficult to manage. neurofibrosarcomatous transformation (malignant) of these in 5-10 % optic nerve gliomas childhood MDS (myelodysplasia) and ANLL, often with monosomy 7 (monosomy 7 syndrome, 'juvenile myelomonocytic leukaemia'): risk, increased by X 200 to 500, is still low, as JMML is rare ; M>F; most often before the age of 5 yrs; no increased risk of leukaemia in the adult. pheochromocytomas various other neoplasias, of which are rhabdomyosarcomas |
| Treatment | early diagnosis, lifetime monitoring and surgery are essential |
| Elevated risk for MPNST in NF1 microdeletion patients. |
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