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Neurofibromatose Typ 2

Klinik und Genetik

Neurofibromatosis type 2

Clinical features and genetic profile

Zusammenfassung

Neurofibromatose Typ 2 (NF2) ist eine genetische Erkrankung, die autosomal-dominant vererbt wird und durch multiple Tumoren des Nervensystems gekennzeichnet ist. Bilaterale vestibuläre Schwannome, bekannt als Akustikusneurinome, sind das Hauptmerkmal der Erkrankung und treten bei etwa 90% der Betroffenen auf. Sie beeinträchtigen das Hörvermögen der Patienten und führen nicht selten zur Ertaubung. Ebenso häufig (>90%) treten bei NF2 spinale Tumoren (Schwannome, Meningiome und Ependymome) auf, die in etwa 1/3 der Fälle zu neurologischen Defiziten führen. Daneben finden sich zerebrale Schwannome und Meningiome als typische NF2-assoziierte Tumormanifestationen. Ferner kennzeichnen Polyneuropathie und okuläre Abnormalitäten das Krankheitsbild. Die genetische Ursache der NF2 ist eine heterozygote Inaktivierung des NF2-Tumorsuppressorgens, welches auf Chromosom 22q lokalisiert ist. Die Inzidenz der NF2 beträgt etwa 1:25.000 Geburten, wobei 50–80% der Patienten keine familiäre Belastung aufweisen. Bei Patienten mit Neumutationen (de novo) wurde eine Mosaikbildung mit überraschend hoher Frequenz (25–30%) nachgewiesen. Der vorliegende Beitrag beschreibt Klinik und Genetik der NF2 sowie aktuelle Entwicklungen in der medikamentösen Therapie.

Abstract

Neurofibromatosis type 2 (NF2) is a genetic autosomal-dominant disorder characterized by multiple benign tumors of the nervous system. Bilateral vestibular schwannomas, known as acoustic neuromas, are the hallmark of NF2 and can be found in more than 90% of patients, causing progressive hearing loss and not infrequently leading to deafness. Spinal tumors (schwannoma, meningioma and ependymoma) develop with similarly high frequency among NF2 patients, while approximately only 1/3 of these lead to neurological symptoms. Cranial non-vestibular schwannomas and meningiomas are also frequent in NF2 patients. The clinical spectrum of NF2 further includes ophthalmological lesions and polyneuropathy. With a birth incidence of around 1 in 25,000, the genetic cause for NF2 is the heterozygous inactivation of the NF2 tumor suppressor gene on 22q. More than half (50%–80%) of NF2 patients are found to bear de novo mutations which are frequently present in a mosaic fashion (25%–30%). This review presents clinical and genetic aspects of NF2, as well as recent developments in its pharmacological treatment.

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Kluwe, L., Mautner, VF. Neurofibromatose Typ 2. medgen 21, 532–538 (2009). https://doi.org/10.1007/s11825-009-0204-5

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Schlüsselwörter

  • NF2
  • Tumorsuppressorgen
  • Vestibuläres Schwannom
  • Mosaikbildung
  • Hörverlust

Keywords

  • NF2
  • Tumor suppressor gene
  • Vestibular schwannoma
  • Mosaicism
  • Hearing loss