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Klinik und Genetik der Neurofibromatose Typ 1

Clinical phenotype and genetics of neurofibromatosis type 1

Zusammenfassung

Die Neurofibromatose Typ 1 (NF1) ist eine autosomal-dominant vererbte Erkrankung. Sie wird durch Mutationen im NF1-Gen auf Chromosom 17q11.2 verursacht. Sie zeigt volle Penetranz, d. h. jeder, der eine Mutation trägt, weist Merkmale der Krankheit auf, jedoch mit z. T. erheblich variabler Expressivität. NF1 ist gekennzeichnet durch die namensgebenden Neurofibrome, bei welchen es sich um gutartige Tumoren der Nervenscheiden handelt. Zu den häufig primär auftretenden Symptomen zählen Pigmentierungsanomalien der Haut, wie Café-au-Lait-Flecken, axilläres bzw. inguinales Freckling, sowie Lisch-Knötchen der Iris. NF1 gehört zur Gruppe der hereditären Tumorerkrankungen. Betroffene weisen ein erhöhtes Risiko auf, an bestimmten NF1-assoziierten Tumoren zu erkranken, die durch eine biallelische Inaktivierung des NF1-Tumorsuppressorgens und aberrante RAS-Signaltransduktion entstehen. In den letzten Jahren sind signifikante Fortschritte bei der Identifizierung und Behandlung der NF1-assoziierten klinischen Symptome sowie in der Entwicklung neuer Therapieansätze zu verzeichnen.

Abstract

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1 gene located on chromosome 17q11.2. NF1 is fully penetrant, meaning that every individual carrying the mutation exhibits symptoms of the disease, although with some considerably variable expressivity. NF1 is characterised by the eponymous neurofibromas, which are benign Schwann cell tumours. Among the other main characteristic features of NF1 are pigmentary anomalies such as café-au-lait spots, axillary or inguinal freckling, and Lisch nodules. NF1 is a member of the class of hereditary cancer syndromes, and patients with NF1 are at increased risk of developing specific NF1-associated tumours. These tumours are caused by the biallelic inactivation of the NF1 tumour suppressor gene, resulting in aberrant Ras regulation. Over the last few years, significant progress has been made in identifying and managing the clinical symptoms of NF1 as well as in developing novel therapeutic approaches.

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Correspondence to H. Kehrer-Sawatzki.

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Kehrer-Sawatzki, H., Mautner, VF. Klinik und Genetik der Neurofibromatose Typ 1. medgen 21, 519 (2009). https://doi.org/10.1007/s11825-009-0191-6

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Schlüsselwörter

  • Neurofibromatose Typ 1
  • Neurokutane Symptomatik
  • Hereditäre Tumorerkrankung
  • Neurofibromin
  • RAS-vermittelte Signaltransduktion

Keywords

  • Neurofibromatosis type 1
  • Neurocutaneous symptoms
  • Hereditary cancer syndrome
  • Neurofibromin
  • Ras-mediated signal transduction