The relationship between patients' perception of the effects of neurofibromatosis type 2 and the domains of the Short Form-36.

OBJECTIVES: To investigate the relationship between those issues concerning quality of life in patients with neurofibromatosis type 2 (NF2) as identified by the closed set NF2 questionnaire and the eight norm-based measures and the physical component summary (PCS) and mental component summary (MCS) scores of the Short Form-36 (SF-36) Questionnaire. DESIGN: Postal questionnaire study. SETTING: Questionnaires sent to subjects' home addresses. PARTICIPANTS: Eighty-seven adult subjects under the care of the Manchester Multidisciplinary NF2 Clinic were invited to participate. MAIN OUTCOME MEASURES: Sixty-two (71%) completed sets of closed set NF2 questionnaires and SF-36 questionnaires were returned. RESULTS: Subjects with NF2 scored less than the norm of 50 on both the physical component summary and mental component summary scores and the eight individual norm-based measures of the Short Form-36 questionnaire. Correlations (using Kendall's tau) were examined between patients' perceptions of their severity of difficulty with the following activities and the eight norm-based measures and the physical component summary and mental component summary scores of the Short Form-36 questionnaire: Communicating with spouse/significant other (N = 61). The correlation coefficients were significant at the 0.01 level for the mental component summary score, together with three of the norm-based scores [vitality (VT), social functioning and role emotional]. Social communication (N = 62). All 10 correlations were significant at the 0.01 or 0.001 level. Balance (N = 59). All 10 correlations were highly significant at the P < 0.001 level. Hearing difficulties (N = 61). All correlations were significant at either the 0.01 level or less apart from the mental component summary score and three of the norm-based scores (role physical, VT and mental health). Mood change (N = 61). All correlations were significant at the 0.01 level or less, apart from one norm-based score (role physical). CONCLUSIONS: The Short Form-36 questionnaire has allowed us to relate patients' perceptions of their difficulties, as identified by the closed set NF2 questionnaire, to the physical and mental domains measured by this validated and widely used scale, and has provided further insight into areas of functioning affected by NF2.

Use of a closed set questionnaire to measure primary and secondary effects of neurofibromatosis type 2.

OBJECTIVES: To identify the greatest difficulties reported by people affected by neurofibromatosis type 2, and to determine the relationship between the primary and secondary effects of the disease. DESIGN: Postal questionnaire study. SETTING: Questionnaire sent to subjects' home addresses. PARTICIPANTS: Eighty-seven adult patients under the care of the Manchester multidisciplinary neurofibromatosis type 2 team were invited to take part. MAIN OUTCOME MEASURE: The response rate was 62 out of 87 (71 per cent). RESULTS: Respondents' answers emphasised that their greatest problem was deafness, which resulted in communication difficulties with social contacts, close partners, family and friends. Correlation coefficients indicated a relationship between general mood changes and hearing difficulties, social communication problems, balance difficulties and mobility problems. Self-confidence was significantly related only to social communication problems. CONCLUSIONS: The use of a closed set neurofibromatosis type 2 questionnaire identified hearing problems and subsequent communication difficulties as the main problems faced by people with this condition.

Molecular genetic analysis of the NF2 gene in young patients with unilateral vestibular schwannomas.

Neurofibromatosis type 2 (NF2) must be suspected in patients presenting with a unilateral vestibular schwannoma at a young age who are therefore at theoretical risk of developing bilateral disease. We identified 45 patients aged 30 years or less at the onset of symptoms of a unilateral vestibular schwannoma. Molecular genetic analysis of the NF2 gene was completed on peripheral blood samples in all 45 and on 28 tumour samples. No pathogenic NF2 mutations were identified in any of the blood samples. NF2 point mutations were identified in 21/28 (75%) tumour samples and loss of heterozygosity (LOH) in 21/28 (75%) tumour samples. Both mutational hits were identified in 18/28 (65%) tumour samples. In one multilobular tumour, one (presumably first hit) mutation was confirmed which was common to different foci of the tumour, while the second mutational event differed between foci. The molecular findings in this patient were consistent with somatic mosaicism for NF2 and the clinical diagnosis was confirmed with the presence of two meningiomas on a follow up MRI scan. A further patient developed a contralateral vestibular schwannoma on a follow up MRI scan in whom neither of the truncating mutations in the vestibular schwannoma were present in blood. It is important when counselling patients with unilateral vestibular schwannomas to identify (1) those at risk of bilateral disease, (2) those at risk of developing other tumours, and (3) other family members at risk of developing NF2. Comparing tumour and blood DNA cannot exclude mosaicism in the index case and cannot, therefore, be used to predict those at risk of developing further tumours. However, identification of both mutations or one mutation plus LOH in the tumour and exclusion of those mutations in the blood samples of the sibs or offspring of the affected case may be sufficient to render further screening unnecessary in these relatives.

A clinical, genetic and audiological study of patients and families with unilateral vestibular schwannomas. II. Audiological findings in 93 patients with unilateral vestibular schwannomas.

Nine-three patients with histologically or radiologically confirmed unilateral vestibular schwannomas were recruited. Audiological testing for retrocochlear pathology was undertaken. Patients' hospital records were examined for previous audiological and radiological results. The audiometric configuration was designated as one of the following: normal, sloping, low frequency, peak, trough or flat. A sloping sensorineural audiometric configuration was present in 68 per cent of cases. No significant correlation was found between tumour size and average pure tone threshold 500 Hz to 4000 Hz, optimum discrimination score or interaural differences for wave V. Ninety-one per cent of cases had abnormalities on auditory evoked potential; 92 per cent of cases showed abnormalities on stapedial reflex testing. The limitations of audiological testing in the investigation of patients with suspected unilateral vestibular schwannomas are discussed. A protocol for the investigation of such patients is presented.

A clinical, genetic and audiological study of patients and families with unilateral vestibular schwannomas. I. Clinical features of neurofibromatosis in patients with unilateral vestibular schwannomas.

Ninety-three patients with unilateral vestibular schwannomas were examined in a clinical, genetic and audiological study, to determine whether they had features associated with neurofibromatosis Type 1 or neurofibromatosis Type 2. In 91 families, one patient only was found to be affected with a unilateral vestibular schwannoma. Patients did have a few café-au-lait macules, but fewer than six in number. None of the patients satisfied the cutaneous diagnostic criteria for neurofibromatosis Type 1. Neither Lisch nodules nor presenile posterior subcapsular lenticular opacities or cortical opacities were a feature. Five patients with unilateral vestibular schwannomas are described where the clinical findings raised the possibility of neurofibromatosis Type 2. It is suggested that certain individuals with unilateral vestibular schwannomas are at risk of developing neurofibromatosis Type 2. Furthermore, the possibility of neurofibromatosis Type 2 should be considered if more than one individual in a family is found to be affected with a unilateral vestibular schwannoma.

A clinical, genetic and audiological study of patients and families with bilateral acoustic neurofibromatosis.

The neurofibromatoses consist of at least two distinct autosomal dominant hereditary disorders. Neurofibromatosis type 1 (NF1) is due to a lesion on chromosome 17q. Neurofibromatosis type 2 (NF2) is caused by a defect on chromosome 22q. The hallmark of NF2 is the development, in the second and third decades, of bilateral acoustic neuromas. NF1 is characterized by the appearance of café-au-lait spots and neurofibromas in addition to iris hamartomas, or Lisch nodules, of the eye, during the first and second decades. Ten families were personally studied. A total of 16 members were found to be affected with NF2. A protocol for evaluation and review of subjects and relatives of NF2 families is proposed. A team approach, coordinating the expertise of multiple specialties is recommended.