Neurofibromatosis Type 2 Clinics and Genetics

Abstract

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterised by multiple benign tumours of the nervous system. More than 90% of the patients develop bilateral vestibular schwannomas, which are the hallmark of NF2 and lead to progressive hearing loss in adult patients. Spinal tumours are as frequent as bilateral vestibular schwannomas, whereas approximately one‐third of them cause neurological symptoms. Cranial nonvestibular schwannomas, meningiomas and ependymomas are also frequent in NF2, as well as ophthalmological lesions and peripheral polyneuropathy. With a birth incidence of around 1 in 25 000, the genetic cause for NF2 is the heterozygous inactivation of the NF2 tumour suppressor gene on 22q. More than half (50–80%) of NF2 patients are founders who bear de novo mutations among whom mosaicism is frequent (at least 25–30%). NF2 is a complex syndrome and demands interdisciplinary care, experienced specialists, social and psychological support and rehabilitation measures.

Key Concepts

  • NF2 is a tumour suppressor gene syndrome and is characterised by multiple benign cerebral and spinal tumours.
  • Bilateral vestibular schwannomas are the hallmark of NF2.
  • The genetic cause for NF2 is the heterozygotic inactivating mutation of the NF2 gene on 22q.
  • Mosaicism is frequent among de novo NF2 patients (>25–30%).
  • NF2 is a complex syndrome and demands interdisciplinary care, experienced specialists, coordinated social and psychological supports and rehabilitation measures.

Keywords: NF2; schwannoma; meningioma; hearing loss; LOH

Figure 1. Bilateral vestibular schwannomas (VS), a cerebral meningioma (M) and multiple spinal tumours (SPT) revealed by MRI in an NF2 patient.
Figure 2. Cutaneous schwannomas in an NF2 patient.
Figure 3. Subcapsular cataract in an NF2 patient.
Figure 4. From classical inherited NF2 to case of sporadic NF2‐related tumours. In between are mosaicism of various timing of mutation, various size of affected cell population, various mutation detecting rate and various severity of the disease.
Figure 5. Tumour‐LOH (loss of heterozygosity) analysis enables identification of the mutation‐bearing allele. Microsatellite marker D22S268 is linked to the NF2 gene. In the blood of the index patient, this marker has two different alleles (with 194 and 196 bp) and is thus heterozygous. The allele 196 bp is lost in the tumour, implying that the tumour retained allele 194 bp bears the genetic defect. Examining the blood DNA (deoxyribonucleic acid) of the offspring of this patient revealed that the patient passed the defective allele 194 bp to offspring No. 1. The other allele 202 bp in offspring No. 1 originates from the other parent. In offspring No. 2, both alleles of the marker were 196 bp. Therefore, this offspring inherited the healthy allele (196 bp) from the affected parent. The other 196 bp allele originates from the other healthy parent.
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Kluwe, Lan, Farschtschi, Said, and Mautner, Victor‐F(Sep 2017) Neurofibromatosis Type 2 Clinics and Genetics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022391.pub2]