Bernasconi A, Regli F, Schorderet D F, Pescia G
Montreal Neurological Institute, Québec, Canada.
Rev Neurol (Paris). 1996 Jun-Jul;152(6-7):447-50.
The major form of familial hyperekplexia, a rare autosomal dominant disorder, is characterized by an abnormal startle reaction elicited by auditory and somatosensory stimuli, with transitory stiffness during the neontam period, followed later by falling attacks accompanied by momentary generalized muscular stiffness. Affected neonates occasionally have fatal hypertonia. The minor form is characterized only by an inconstant excessive startle response. We encountered a family in which three females presented with a partial or complete major form of the disease. All our patients were hyperreflexic, insecure gait was present in two subjects, without concomitant spontaneous nocturnal myoclonus. The pathophysiological basis of the hyperekplexia remains unclear. The abnormal startle reflex, probably related to the lack of inhibition by higher centers, is relayed in the caudal brainstem (ponto-medullary reticular formation), where bulbospinal motor efferents originate. Moreover, nonspecific changes such as large somatosensory evoked potentials and long-loop reflexes ("C-responses") may indicate increased cortical neuronal excitability. Polygraphic studies in these patients were normal. The locus of the major form of the disorder is located on chromosome 5q33-q35. Sequence analysis of the alpha 1 subunit of the inhibitory glycine receptor (GLRA1) revealed a mutation at the same codon 271 in several families (G1192A and G1192T). We analyzed this gene and found a G1192A mutation changing an ARG to a LEU codon in all three presented patients. Sporadic cases may represent new mutations or lack of penetrance in some family members. Only one of our three patients needed clonazepam. The diagnosis of this disorder rules out epilepsy, or psychogenic pathological startle reaction. Electrophysiological criteria are useful, however perinatal hypertonia or a tonic generalized spasm accompanied with falls following an abnormal startle reaction and genetic studies remain the diagnostic milestones of familial hyperekplexia.
家族性惊吓症是一种罕见的常染色体显性疾病，其主要形式的特征是由听觉和躯体感觉刺激引发异常惊吓反应，新生儿期有短暂僵硬，随后出现跌倒发作并伴有瞬间全身性肌肉僵硬。患病新生儿偶尔会出现致命性肌张力亢进。次要形式仅表现为不恒定的过度惊吓反应。我们遇到一个家族，其中三名女性表现出部分或完全的主要疾病形式。我们所有的患者都有反射亢进，两名患者存在步态不稳，且无夜间自发性肌阵挛。惊吓症的病理生理基础尚不清楚。异常惊吓反射可能与高级中枢抑制缺乏有关，在延髓尾端脑干（脑桥 - 延髓网状结构）传导，此处是延髓脊髓运动传出神经的起源地。此外，诸如体感诱发电位增大和长环反射（“C反应”）等非特异性变化可能表明皮质神经元兴奋性增加。这些患者的多导睡眠图研究结果正常。该疾病主要形式的致病基因位点位于5号染色体q33 - q35区域。对抑制性甘氨酸受体（GLRA1）α1亚基的序列分析显示，多个家族在相同密码子271处存在突变（G1192A和G1192T）。我们对该基因进行分析，发现所有三名患者均存在G1192A突变，该突变使精氨酸密码子变为亮氨酸密码子。散发病例可能代表新的突变或某些家庭成员缺乏外显率。我们三名患者中只有一人需要使用氯硝西泮。该疾病的诊断可排除癫痫或心因性病理性惊吓反应。电生理标准很有用，然而围生期肌张力亢进或伴有异常惊吓反应后的跌倒发作的强直性全身痉挛以及基因研究仍然是家族性惊吓症的诊断关键。
