BackgroundGermline pathogenic variants in SDHB/SDHC/SDHD are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype–phenotype correlations in a large cohort of SDHB/SDHC/SDHD mutation carriers.MethodsA retrospective survey of 1832 individuals referred for genetic testing due to a personal or family history of phaeochromocytoma/paraganglioma. 876 patients (401 previously reported) had a germline mutation in SDHB/SDHC/SDHD (n=673/43/160). Tumour risks were correlated with in silico structural prediction analyses.ResultsTumour risks analysis provided novel penetrance estimates and genotype–phenotype correlations. In addition to tumour type susceptibility differences for individual genes, we confirmed that the SDHD:p.Pro81Leu mutation has a distinct phenotype and identified increased age-related tumour risks with highly destabilising SDHB missense mutations. By Kaplan-Meier analysis, the penetrance (cumulative risk of clinically apparent tumours) in SDHB and (paternally inherited) SDHD mutation-positive non-probands (n=371/67 with detailed clinical information) by age 60 years was 21.8% (95% CI 15.2% to 27.9%) and 43.2% (95% CI 25.4% to 56.7%), respectively. Risk of malignant disease at age 60 years in non-proband SDHB mutation carriers was 4.2%(95% CI 1.1% to 7.2%). With retrospective cohort analysis to adjust for ascertainment, cumulative tumour risks for SDHB mutation carriers at ages 60 years and 80 years were 23.9% (95% CI 20.9% to 27.4%) and 30.6% (95% CI 26.8% to 34.7%).ConclusionsOverall risks of clinically apparent tumours for SDHB mutation carriers are substantially lower than initially estimated and will improve counselling of affected families. Specific genotype–tumour risk associations provides a basis for novel investigative strategies into succinate dehydrogenase-related mechanisms of tumourigenesis and the development of personalised management for SDHB/SDHC/SDHD mutation carriers.

A consensus conference on neurofibromatosis 2 (NF2) was held in 2002 at the request of the United Kingdom (UK) Neurofibromatosis Association, with particular emphasis on vestibular schwannoma (VS) surgery. NF2 patients should be managed at specialty treatment centres, whose staff has extensive experience with the disease. All NF2 patients and their families should have access to genetic testing because presymptomatic diagnosis improves the clinical management of the disease. Some clinical manifestations of NF2, such as ocular abnormalities, can be detected in infancy; therefore, clinical screening for at-risk members of NF2 families can start at birth, with the first magnetic resonance (MRI) scan at 10-12 years of age. Minimal interference, maintenance of quality of life, and conservation of function or auditory rehabilitation are the cornerstones of NF2 management, and the decision points to achieve these goals for patients with different clinical presentations are discussed.

The authors recommend the use of fluid-attenuated inversion recovery and diffusion sequence MRI when definitive radiologic diagnosis of cystic intracranial lesions becomes difficult with routine computerized tomographic scanning and MRI.

A prospective analysis of patients referred by Otolaryngologists from a tertiary hospital for detailed assessment of the posterior cranial fossa was undertaken. The objectives were to evaluate radiological characteristics of the anterior inferior cerebellar artery (AICA) within the cerebellopontine angle (CPA) and the internal auditory canal (IAC), and to correlate these characteristics with ipsilateral auditory symptoms. Three hundred and thirty-two consecutive adult patients who presented with unilateral auditory symptoms were studied. All patients were referred by the Department of Otolaryngology at City Hospital, Birmingham, from October 1999 to October 2001. Magnetic resonance imaging (MRI) with three-dimensional Fourier Transformation Constructive Interference in Steady State (3D FT-CISS) was the imaging strategy used to investigate each patient. Six hundred and sixty-four sides were studied and the AICA loop was identified in all patients. Using a simple anatomical classification to type the loops: there were 412 type I loops (within the CPA), 202 type II loops (at the porus acousticus, extending up to 50% of IAC) and 50 type III loops (extending beyond 50% of IAC). There was a statistically significant association with unilateral hearing loss and type II and III AICA loops (P = 0.016 and P = 0.006 respectively). An association between the presence of a large diameter vascular loop in the CPA and unilateral auditory symptoms was not found to be significant (P > 0.05).

The results of this study have demonstrated a more favorable hearing outcome for patients with intracanalicular tumors and tumors extending up to 1 cm into the CPA that were removed via the MF when compared with the RS approach.