Lafora disease in miniature Wirehaired Dachshunds

Lafora disease (LD) is an autosomal recessive late onset, progressive myoclonic epilepsy with a high prevalence in the miniature Wirehaired Dachshund. The disease is due to a mutation in the Epm2b gene which results in intracellular accumulation of abnormal glycogen (Lafora bodies). Recent breed-wide testing suggests that the carrier plus affected rate may be as high as 20%. A characteristic feature of the disease is spontaneous and reflex myoclonus; however clinical signs and disease progression are not well described. A survey was submitted to owners of MWHD which were homozygous for Epm2b mutation (breed club testing program) or had late onset reflex myoclonus and clinical diagnosis of LD. There were 27 dogs (11 male; 16 female) for analysis after young mutation-positive dogs that had yet to develop disease were excluded. Average age of onset of clinical signs was 6.94 years (3.5–12). The most common initial presenting sign was reflex and spontaneous myoclonus (77.8%). Other presenting signs included hypnic myoclonus (51.9%) and generalized seizures (40.7%). Less common presenting signs include focal seizures, “jaw smacking”, “fly catching”, “panic attacks”, impaired vision, aggression and urinary incontinence. All these clinical signs may appear, and then increase in frequency and intensity over time. The myoclonus in particular becomes more severe and more refractory to treatment. Signs that developed later in the disease include dementia (51.9%), blindness (48.1%), aggression to people (25.9%) and dogs (33.3%), deafness (29.6%) and fecal (29.6%) and urinary (37.0%) incontinence as a result of loss of house training (disinhibited type behavior). Further prospective study is needed to further characterize the canine disease and to allow more specific therapeutic strategies and to tailor therapy as the disease progresses.拉福拉病（Lafora disease, LD）是一种常染色体隐性遗传的迟发性进行性肌阵挛癫痫，在迷你刚毛腊肠犬（Miniature Wirehaired Dachshund，下文简称MWHD）中患病率较高。该病由Epm2b基因突变引发，可导致细胞内异常糖原蓄积并形成拉福拉小体（Lafora bodies）。近期全品种检测结果显示，该疾病的携带者与患病犬合计比例最高可达20%。 该病的典型特征为自发性与反射性肌阵挛，但目前针对其临床症状与疾病进展的描述仍较为有限。本研究针对MWHD犬主发起了一项调研，受试对象为经品种俱乐部检测项目确认携带Epm2b基因突变纯合子，或表现出迟发性反射性肌阵挛且经临床确诊为LD的犬只。本研究排除了尚未出现临床症状的年轻突变阳性犬只，最终纳入27只受试犬（公犬11只、母犬16只）进行分析。受试犬的临床症状平均发病年龄为6.94岁（范围3.5~12岁）。 最常见的初始临床表现为反射性与自发性肌阵挛（占比77.8%），其他初始症状包括睡眠期肌阵挛（51.9%）与全身性癫痫发作（40.7%）；较为少见的初始症状则包括局灶性癫痫发作、“咂嘴”、“抓飞虫”、“惊恐发作”、视力减退、攻击性行为及尿失禁。上述所有临床症状均可能随时间推移出现频率升高、强度加剧的变化，其中肌阵挛症状尤为严重，且对治疗的耐药性更强。 疾病后期可出现的症状包括痴呆（51.9%）、失明（48.1%）、对人类（25.9%）与其他犬只（33.3%）的攻击性增强、耳聋（29.6%），以及因丧失如厕训练能力（失抑制行为）引发的粪便失禁（29.6%）与尿失禁（37.0%）。本研究认为，仍需开展进一步前瞻性研究以全面阐明犬类拉福拉病的临床特征，从而制定更具针对性的治疗方案，并可根据疾病进展情况调整治疗策略。