Sainio M, Strachan T, Blomstedt G, Salonen O, Setälä K, Palotie A, Palo J, Pyykkö I, Peltonen L, Jääskeläinen J
Department of Neurology, University of Helsinki, Finland.
Neurology. 1995 Jul;45(7):1314-22. doi: 10.1212/wnl.45.7.1314.
Neurofibromatosis 2 (NF2), a dominantly inherited disorder, typically manifests as bilateral vestibular schwannomas and predisposes to other nervous system tumors. In this study, we present a large pedigree with a benign course of NF2 (mild Gardner type) characterized by slowly growing vestibular schwannomas but few other manifestations. The family was thoroughly investigated with neurologic, ophthalmologic, and neuro-otologic methods including gadolinium-enhanced MRI of the head and spine and DNA linkage analysis. In the clinical analysis of 22 family members, MRI was superior to neuro-otologic methods in the detection of asymptomatic tumors. Based on the DNA linkage analyses we identified the NF2 mutation carriers with a high degree of certainty. These DNA markers (CRYB2, NEFH, D22S268, and D22S280) can also be used for presymptomatic diagnosis in other NF2 families. Early detection of NF2 gene mutation carriers has become possible using linkage analysis in familial NF2. MRI screening of carriers will reveal presymptomatic vestibular schwannomas (and other CNS tumors), making early intervention possible, but an efficient treatment strategy to prevent deafness has not yet been established.
神经纤维瘤病2型（NF2）是一种常染色体显性遗传病，通常表现为双侧前庭神经鞘瘤，并易患其他神经系统肿瘤。在本研究中，我们展示了一个具有良性病程的NF2（轻度加德纳型）大家族，其特征为前庭神经鞘瘤生长缓慢，但其他表现较少。我们采用神经学、眼科和神经耳科学方法对该家族进行了全面调查，包括头部和脊柱的钆增强磁共振成像（MRI）以及DNA连锁分析。在对22名家族成员的临床分析中，MRI在检测无症状肿瘤方面优于神经耳科学方法。基于DNA连锁分析，我们高度确定地识别出了NF2突变携带者。这些DNA标记（CRYB2、NEFH、D22S268和D22S280）也可用于其他NF2家族的症状前诊断。利用家族性NF2的连锁分析，现已能够早期检测NF2基因突变携带者。对携带者进行MRI筛查将发现症状前前庭神经鞘瘤（及其他中枢神经系统肿瘤），从而使早期干预成为可能，但尚未确立预防耳聋的有效治疗策略。
