病例报告：由新型复合杂合FBXO7变异引起的新生儿起病帕金森-锥体综合征

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中文摘要

背景： 早发性帕金森综合征常与遗传因素相关。FBXO7基因的致病性变异是早发性帕金森综合征的罕见原因，通常表现为帕金森-锥体综合征（PPS），也称为帕金森病-15（PARK15）。迄今为止，全球仅报道了三例婴儿期起病的PARK15病例。在此，我们描述了一名携带新型复合杂合FBXO7变异的新生儿起病PARK15的中国患者。
病例介绍： 一名37小时大的男婴因全身肢体僵硬被转诊评估新生儿起病的高肌张力。体格检查发现异常发声、吸吮和吞咽不良（需要鼻胃管喂养）以及腹肌僵硬。锥体束受累表现为巴宾斯基征及其等位征阳性，伴有反射亢进，而锥体外系表现包括四肢铅管样僵硬，肌张力显著增高。全外显子组测序鉴定出FBXO7基因的两个复合杂合无义变异，c.376G > T（p.Gly126*）和c.1033C > T（p.Arg345*），分别遗传自父亲和母亲。两个变异均被分类为致病性。诊断后，父母选择停止积极的住院治疗，婴儿被带回家中。尽管如此，在家中开始了口服左旋多巴的试验。尽管接受了左旋多巴治疗，婴儿未见临床改善，并于89天龄时死亡。
结论： 据我们所知，这是首例由FBXO7变异引起的新生儿起病PARK15的报道病例。该病例扩展了PARK15在新生儿期的突变谱和临床谱。

英文摘要

BACKGROUND: Early-onset parkinsonism is often associated with genetic factors. Pathogenic variants in the FBXO7 gene are a rare cause of early-onset parkinsonism, typically presenting as parkinsonian-pyramidal syndrome (PPS), also known as Parkinson's disease-15 (PARK15). To date, only three cases of infantile-onset PARK15 have been reported worldwide. Herein, we describe a Chinese patient with neonatal-onset PARK15, who carried novel compound heterozygous FBXO7 variants.
CASE PRESENTATION: A 37-hour-old male infant with generalized limb rigidity was referred for evaluation of neonatal-onset hypertonia. Physical examination revealed abnormal vocalization, poor sucking and swallowing (requiring nasogastric tube feeding), and abdominal muscle rigidity. Pyramidal involvement was evidenced by positive Babinski sign and its equivalents, together with hyperreflexia, while extrapyramidal findings included lead-pipe rigidity of all four limbs with markedly increased muscle tone. Whole-exome sequencing identified two compound heterozygous nonsense variants in FBXO7, c.376G > T (p.Gly126*) and c.1033C > T (p.Arg345*), inherited from the father and mother, respectively. Both variants were classified as pathogenic. Following diagnosis, the parents elected to discontinue active in-hospital treatment, and the infant was discharged home. Nevertheless, a trial of oral levodopa was initiated at home. Despite levodopa treatment, the infant showed no clinical improvement and died at 89 days of age.
CONCLUSIONS: To our knowledge, this is the first reported case of neonatal-onset PARK15 caused by FBXO7 variants. This case expands the mutational and clinical spectrum of PARK15 in the neonatal period.