Neurofibromatosis type 2

Abstract

Neurofibromatosis type 2 is an autosomal-dominant multiple neoplasia syndrome that results from mutations in the NF2 tumour suppressor gene located on chromosome 22q. It has a frequency of one in 25 000 livebirths and nearly 100% penetrance by 60 years of age. Half of patients inherit a germline mutation from an affected parent and the remainder acquire a de novo mutation for neurofibromatosis type 2. Patients develop nervous system tumours (schwannomas, meningiomas, ependymomas, astrocytomas, and neurofibromas), peripheral neuropathy, ophthalmological lesions (cataracts, epiretinal membranes, and retinal hamartomas), and cutaneous lesions (skin tumours). Optimum treatment is multidisciplinary because of the complexities associated with management of the multiple, progressive, and protean lesions associated with the disorder. We review the molecular pathogenesis, genetics, clinical findings, and management strategies for neurofibromatosis type 2.

Empirical development of improved diagnostic criteria for neurofibromatosis 2

“…1,2 The detection rate is approximately 60% in de novo (simplex) cases because 25-30% of such cases are mosaic. 11,12 Some clinical laboratories may use less sensitive methods for detecting pathogenic mutations of the NF2 locus; this would delay the diagnosis of NF2 in a few patients until it can be made on the basis of clinical features alone.…”

“…17,18 Deterioration of hearing is not correlated with rate of VS tumor growth in NF2, 19 and careful monitoring of both hearing and tumor growth is necessary in patients with NF2. 1,2 The UK NF2 Registry is population based and has several sources of ascertainment, 4 so it is likely to be more similar to the overall NF2 patient population than if the subjects had been identified through a single clinic or hospital. However, both the training and holdout subsets were drawn from the same source, so if subjects in the Registry differ from the NF2 patient Calculation of sensitivity and specificity was based on 67 patients with definite NF2 and 142 who definitely do not have NF2 at the age of onset of the first characteristic sign of NF2.…”

“…Since 1997, when the most recent set of diagnostic criteria were proposed, the natural history of NF2 has become more clearly defined, 19 -24 and management of the disease has improved. 1,2,25-27 Molecular testing for NF2 mutations has become clinically available, 1,2,26,28,29 and somatic mosaicism has been found to occur in 25-30% of de novo NF2 patients. 11,12 Schwannomatosis has been defined as a distinct clinical entity, 9 excluded from the NF2 locus, 30 and shown to be related to mutations of the SMARCB1 locus in some patients.…”

“…1,2 Clinical characteristics of NF2 include vestibular schwannomas (VS), intracranial meningiomas, spinal tumors (usually schwannomas or meningiomas), peripheral nerve schwannomas, and ocular abnormalities. Early diagnosis is often difficult in patients with de novo constitutional mutations, who comprise half of people with NF2.…”

Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms

“…An additional form of neurofibromatosis is neurofibromatosis type 2, which is caused by mutations in NF2, encoding the merlin protein. Neurofibromatosis type 2 is generally characterized by tumors within the brain, cranial nerves, and spinal cord [69]. Although related, it is a disorder distinct from NF1, with few current publications addressing a potential association with autistic symptoms [70].…”