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 1/3 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 which are present in a mosaic fashion in at least 25–30% of the patients. NF2 is a complex syndrome and demands interdisciplinal 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 interdisciplinal care, experienced specialists, coordinated social and psychological supports and rehabilitation measures.