Neurofibromatosis peripheral Q85.0

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

Neurofibromatosis type I; NFI

Definition
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Hereditary, autosomal-dominantly inherited neuroectodermal systemic disease, also caused by spontaneous mutation.

Occurrence/Epidemiology
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Prevalence 1:3,500; low androtrophy

Etiopathogenesis
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Autosomal dominant inheritance. Mutation of the q11.2 gene locus on chromosome 17, said NF1 gene locus comprising three genes: OMPG (coding for a membrane-bound glycoprotein of oligodendrocyte myelin), EVI2A and EVI2B (coding for viral insertion sequences).

The NF1 peptide shows sequence homologies with the GTPase-activating protein (GAP) and stimulates the GTPase activity of Ras.

When GTPases are activated, they hydrolyse GTP to GDP and as such are no longer able to stimulate their effector. Defective GAPs are no longer able to switch off a mitogenic signal and the cells proliferate uncontrollably.

Manifestation
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The appearance of café-au-lait stains is possible from birth, but mostly in the first months of life until the age of 2. Dermal neurofibromas only develop later between the ages of 10 and 16.

Clinical features
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  • Pigmented spots:
    • Café-au-lait stains (> 95% of cases): about 80% of patients have > 6 café-au-lait stains. However, this symptom can also occur in 10% of the unaffected population.
    • Axillary freckling (about 90% of patients; = Crowe's sign); pigmentation of the oral mucosa.
    • Naevi: Melanocytic naevi (occurrence less than in the average population)
    • The occurrence of hemangiomas, lymphangiomas, lentigines and naevi spili is also possible
    • In >50% of patients with neurofibromatosis type I a N. anaemicus is found gfls. together with a juvenile xanthogranuloma.
  • Single or numerous, pea-sized or monstrous, skin-coloured to bluish, broad or stalked papules or nodules (neurofibromas), possibly with wrinkles or as dewlap-like formations, cutis laxa.
    • Bell-button phenomenon: subcutaneous tumors protruding like hernia through the skin can be pushed back with one finger.
    • In addition, there are also deeper subcutaneous neurofibromas, which are often pressure-dolent and are more difficult to palpate.
  • Neurology: Tumours of the CNS and neurological symptoms appear as serious problems with NF-1. Especially tumors of the cranial nerves may require surgical intervention. Acoustic and trigeminal neurinomas cause especially hearing loss but also pain. Optic gliomas can cause unilateral blindness; tumours of the spinal roots can cause paralysis and pain.
  • Eyes: Mostly exophthalmus and Lisch nodules.
    • Lisch nodules (Irishamartomas): Small, roundish, sharply defined and slightly raised changes in the iris. They have a light, yellowish to brownish hue. They are considered an important diagnostic criterion in peripheral neurofibromatosis and occur in almost all patients with neurofibromatosis type I (> 20 years). They do not occur in NFII, NFIII and NFIV.
  • Skeleton: Changes occur in 1/3 of the patients as thickening and lengthening of the tubular bones, kyphoscoliosis (maldevelopment of the vertebral bodies), bone cysts, pathological fractures and habitual luxations. Furthermore: malformation and deformation of the skull.
  • All other tumours (spinal and peripheral neurofibromas, peripheral nerve schwannomas, etc.) are found in less than 5% of patients. About one third of patients also have non-specific symptoms such as school problems (30%), short stature (15%), macrocephaly (25%) and scoliosis (30%). Pseudoarthroses and epilepsies occur in less than 5% of patients. A part of the patients develop a pheochromocytoma.
  • Notice! Diagnostic criteria include the symptoms that the vast majority of patients experience during the course of the disease. However, not all patients develop all these symptoms, but only a more or less random combination of them. Doctors make a statistically skilful selection of average symptoms and use these as diagnostic criteria to predict whether a person has the particular disease.

Histology
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Diagnosis
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General therapy
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  • Since peripheral neurofibromatosis (NF type I) is a genetic disease, a therapy aimed at curing the underlying disorder is currently not possible.
  • The only treatment option is therefore surgical removal of the cutaneous neurofibromas.
  • Tumours of the central nervous system can be localised in such a way that a surgical procedure is not possible without changes to healthy tissue. There is also the possibility that surgery and radiation may promote tumour growth. Therefore, a very precise risk-benefit assessment is required. Usually only those changes are removed that have the risk of malignant development. Other reasons for surgery include severe neurological or orthopaedic symptoms, serious cosmetic problems and the threat of blindness.

Operative therapie
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Smaller cutaneous neurofibromas can be excised without problems. Good cosmetic results are also achieved by laser ablation (CO2 or Erbium YAG laser).

Progression/forecast
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  • Due to the genetic mechanisms of the disease, all symptoms of the disease only develop over time. In this sense there is also a progression. The diversity of genetic findings is accompanied by a variety of symptoms and courses of the disease.
  • The mortality of patients is generally increased.
  • Because of the autosomal dominant inheritance, a critical review of the desire for children is recommended. Fertility disorders seem to occur.

Literature
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  1. Meissner M et al (2011) Fast and effective treatment of smaller neurofibromas. JDDG 9: 167-169

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

Authors

Last updated on: 29.10.2020