Abstract：
Hereditary spastic paraplegia (HSP) encompasses several rare genetic disorders characterized by progressive lower extremity spasticity and weakness caused by corticospinal tract degeneration. Published literature on genetically confirmed pediatric HSP cases is limited.
We conducted a retrospective review of childhood-onset HSP cases followed in the neuromuscular clinics at Children\'s and Emory Healthcare in Atlanta. Clinical presentation, family history, examination, electrodiagnostic data, neuroimaging, genetic test results, comorbidities, and treatment were recorded.
Sixteen patients with HSP (eight males, eight females) with a mean age 19 years ± 15.7 years were included. Ten patients (66%) presented with gait difficulty. Seven (44%) were ambulatory at the last clinic follow-up visit with an average disease duration of 7.4 years. Genetically confirmed etiologies included SPAST (3 patients), MARS (2), KIF1A (2), KIF5A (1), SACS (1), SPG7 (1), REEP1 (1), PNPT1 (1), MT-ATP6 (1), and ATL1 (1). Symptom onset to genetic confirmation on an average was 8.2 years. Sensory motor axonal polyneuropathy was found in seven patients, and two exhibited cerebellar atrophy on magnetic resonance imaging (MRI) of the brain. Neurological comorbidities included developmental delay (n = 9), autism (n = 5), epilepsy (n = 3), and attention-deficit/hyperactivity disorder (n = 2).
In our study, a significant proportion (70%) of subjects with childhood-onset HSP had comorbid neurocognitive deficits, polyneuropathy with or without neuroimaging abnormalities, and rare genetic etiology. Genetic diagnosis was established either through inherited genetic neuropathy panel or whole-exome sequencing, which supports the utility of whole-exome sequencing in aiding in HSP diagnosis.
We conducted a retrospective review of childhood-onset HSP cases followed in the neuromuscular clinics at Children\'s and Emory Healthcare in Atlanta. Clinical presentation, family history, examination, electrodiagnostic data, neuroimaging, genetic test results, comorbidities, and treatment were recorded.
Sixteen patients with HSP (eight males, eight females) with a mean age 19 years ± 15.7 years were included. Ten patients (66%) presented with gait difficulty. Seven (44%) were ambulatory at the last clinic follow-up visit with an average disease duration of 7.4 years. Genetically confirmed etiologies included SPAST (3 patients), MARS (2), KIF1A (2), KIF5A (1), SACS (1), SPG7 (1), REEP1 (1), PNPT1 (1), MT-ATP6 (1), and ATL1 (1). Symptom onset to genetic confirmation on an average was 8.2 years. Sensory motor axonal polyneuropathy was found in seven patients, and two exhibited cerebellar atrophy on magnetic resonance imaging (MRI) of the brain. Neurological comorbidities included developmental delay (n = 9), autism (n = 5), epilepsy (n = 3), and attention-deficit/hyperactivity disorder (n = 2).
In our study, a significant proportion (70%) of subjects with childhood-onset HSP had comorbid neurocognitive deficits, polyneuropathy with or without neuroimaging abnormalities, and rare genetic etiology. Genetic diagnosis was established either through inherited genetic neuropathy panel or whole-exome sequencing, which supports the utility of whole-exome sequencing in aiding in HSP diagnosis.
摘要：
遗传性痉挛性截瘫（HSP）包括几种罕见的遗传性疾病，其特征是进行性下肢痉挛和皮质脊髓束变性引起的无力。关于遗传证实的小儿HSP病例的已发表文献有限。
我们对亚特兰大儿童和埃默里医疗的神经肌肉诊所的儿童期发病HSP病例进行了回顾性回顾。临床表现,家族史,考试,电诊断数据,神经影像学,基因检测结果,合并症,并记录治疗情况。
16例HSP患者（8例男性，包括8名女性），平均年龄19岁±15.7岁。10例患者（66％）出现步态困难。在最后一次临床随访中，有7人（44％）在门诊就诊，平均病程为7.4年。遗传证实的病因包括SPAST（3例），火星(2),KIF1A(2),KIF5A(1),SACS(1),SPG7(1),REEP1(1),PNPT1(1),MT-ATP6(1),ATL1(1)遗传确认的症状发作平均为8.2年。在7名患者中发现了感觉运动型轴索多发性神经病，两个人在大脑的磁共振成像（MRI）上表现出小脑萎缩。神经系统合并症包括发育迟缓（n=9），自闭症（n=5），癫痫（n=3），和注意力缺陷/多动障碍（n=2）。
在我们的研究中,显著比例（70%）的儿童期发病的HSP受试者患有共病的神经认知缺陷，伴有或不伴有神经影像学异常的多发性神经病,和罕见的遗传病因。基因诊断是通过遗传性遗传性神经病小组或全外显子组测序建立的，这支持全外显子组测序在HSP诊断中的应用。
我们对亚特兰大儿童和埃默里医疗的神经肌肉诊所的儿童期发病HSP病例进行了回顾性回顾。临床表现,家族史,考试,电诊断数据,神经影像学,基因检测结果,合并症,并记录治疗情况。
16例HSP患者（8例男性，包括8名女性），平均年龄19岁±15.7岁。10例患者（66％）出现步态困难。在最后一次临床随访中，有7人（44％）在门诊就诊，平均病程为7.4年。遗传证实的病因包括SPAST（3例），火星(2),KIF1A(2),KIF5A(1),SACS(1),SPG7(1),REEP1(1),PNPT1(1),MT-ATP6(1),ATL1(1)遗传确认的症状发作平均为8.2年。在7名患者中发现了感觉运动型轴索多发性神经病，两个人在大脑的磁共振成像（MRI）上表现出小脑萎缩。神经系统合并症包括发育迟缓（n=9），自闭症（n=5），癫痫（n=3），和注意力缺陷/多动障碍（n=2）。
在我们的研究中,显著比例（70%）的儿童期发病的HSP受试者患有共病的神经认知缺陷，伴有或不伴有神经影像学异常的多发性神经病,和罕见的遗传病因。基因诊断是通过遗传性遗传性神经病小组或全外显子组测序建立的，这支持全外显子组测序在HSP诊断中的应用。
