Ryan S G, Sherman S L, Terry J C, Sparkes R S, Torres M C, Mackey R W
Department of Pediatrics (Neurology), University of Texas Health Science Center, San Antonio 78284-7814.
Ann Neurol. 1992 Jun;31(6):663-8. doi: 10.1002/ana.410310615.
Familial startle disease (also known as hyperekplexia and congenital "stiff-man" syndrome) is an autosomal dominant disorder characterized by an exaggerated startle reaction of sudden, unexpected auditory or tactile stimuli; affected neonates also have severe and occasionally fatal hypertonia. We recently encountered a large, five-generation family with startle disease, and treated 16 patients (including 1 neonate) with clonazepam; all experienced dramatic and sustained improvement. We performed systematic linkage analysis in this family, and found tight linkage between the disease locus and a polymorphic genetic marker locus (colony-stimulating factor receptor, or CSF1R) that has been physically mapped to chromosome 5q33-q35. The maximum odds ratio favoring linkage over nonlinkage is greater than 10,000,000:1 (lod score, 7.10) at 3% recombination. Several genes encoding neurotransmitter receptor components have been physically mapped to the subtelomeric region of chromosome 5q, and are thus candidates for the startle disease gene. The availability of additional large pedigrees with startle disease should facilitate identification and characterization of the gene for this disorder.
家族性惊吓病（也称为僵人综合征和先天性“僵人”综合征）是一种常染色体显性疾病，其特征为对突然、意外的听觉或触觉刺激产生夸张的惊吓反应；患病新生儿还会出现严重且偶尔致命的张力亢进。我们最近遇到了一个患有惊吓病的五代大家庭，并使用氯硝西泮治疗了16名患者（包括1名新生儿）；所有人的病情都有显著且持续的改善。我们对这个家族进行了系统的连锁分析，发现疾病位点与一个已在物理图谱上定位到5号染色体q33 - q35区域的多态性遗传标记位点（集落刺激因子受体，即CSF1R）紧密连锁。在3%重组率时，支持连锁而非非连锁的最大优势比大于10000000:1（连锁对数，7.10）。几个编码神经递质受体成分的基因已在物理图谱上定位到5号染色体q的亚端粒区域，因此是惊吓病基因的候选基因。获得更多患有惊吓病的大型家系应有助于鉴定和表征这种疾病的基因。
