家族性正常钾性周期性瘫痪和遗传性痉挛性截瘫伴薄胼胝体共存一家系报告

A family report of co-exist familial normal kalemic periodic and hereditary spastic paraplegia with thin corpus callosum

目的总结正常钾性周期性瘫痪(normal kalemic periodic paralysis,normoKPP)和遗传性痉挛性截瘫伴薄胼胝体(hereditary spastic paraplegia with thin corpus callosum,HSP-TCC)共存一家系患者的临床、病理及遗传学特点。方法收集患者详细的临床资料,绘制家系图。先证者行右侧肱二头肌病理检查。对先证者及家系部分成员抽取静脉血提取DNA,先证者行遗传性肌病和痉挛性截瘫基因二代测序,其父母和弟弟行异常基因验证。结果该家系有近亲结婚史,家系中连续3代患者共9例,其中单纯normoKPP 8例,normoKPP和HSP-TCC共存1例(先证者Ⅴ4)。临床表现为发作性肢体无力,持续数小时至数天,补钾后症状可消失。先证者同时存在剪刀步态、智能低下及视力下降。先证者头颅MRI示胼胝体发育不良。先证者肌肉病理可见到肌纤维内空泡样改变及管聚集现象。先证者存在normoKPP CACNA1S基因c.1583G>A的杂合核苷酸变异及SPG11基因c.733-734del的纯合核苷酸变异,先证者母亲(Ⅳ9)存在CACNA1S基因c.1583G>A和SPG11基因c.733-734del的杂合核苷酸变异;先证者父亲(Ⅳ10)存在SPG11基因c.733-734del的杂合核苷酸变异;先证者弟弟(Ⅴ5)存在CACNA1S基因c.1583G>A的杂合核苷酸变异。结论确诊了由CACNA1S基因突变导致的normoKPP家系和SPG11基因突变导致的HSP-TCC家系共存,明确了先证者的致病基因突变类型。normoKPP家系的先证者肌肉病理可见管聚集和空泡样改变。

Objective To summarize the clinical,pathological and genetic characteristics of normal kalemic periodic paralysis(normoKPP)and hereditary spastic paraplegia with thin corpus callosum(HSP-TCC)co-existing patients.Methods The detailed clinical data of members in the family were collected and the pedigree was drawn.Pathological examination of the right biceps was performed on the proband.The venous blood was extracted from the proband and some members of the family.The proband performed second-generation sequencing of hereditary myopathy and spastic paraplegia,and their parents and brothers performed abnormal gene validation.Results The family had a history of close relatives’marriage.There were nine consecutive patients in the three successive generations of the family.There were eighe cases of simple normoKPP,and one case of normoKPP and HSP-TCC coexist(probandⅤ4).The clinical manifestation included paroxysmal limb weakness,lasting several hours to several days,and the symptoms might disappear after potassium supplementation.The probands also had scissors gait,low intelligence,and decreased vision.The cranial images of the proband showed poor development of the corpus callosum.Muscle pathology of the proband showed vacuolar changes and tube aggregation in muscle fibers.The proband had a heterozygous nucleotide variation of the normoKPP CACNA1 S gene c.1583 G>A and a homozygous nucleotide variant of the SPG11 gene c.733-734 del.The CACNA1 S gene c.1583 G>A and heterozygous nucleotide variations of SPG11 Gene c.733-734 del were present in the proband’s mother(Ⅳ9).The heterozygous nucleotide variation of SPG11 gene c.733-734 del existed in the proband’s father(Ⅳ10);the heterozygous nucleotide variation of CACNA1 S gene c.1583 G>A existed in the proband’s younger brother(Ⅴ5).Conclusions A co-existence of the HSP-TCC family caused by mutations in the gene CACNA1 S and the normoKPP family caused by mutations in the gene SPG11 is confirmed.The type of pathogenic gene mutation in the proband is identified.Muscular pathology of the proband of the normoKPP family shows vacuolar changes and tube aggregation in muscle fibers.