Beysen Diane, De Cordt Chania, Dielman Charlotte, Ogunjimi Benson, Dandelooy Julie, Reyniers Edwin, Janssens Katrien, Meuwissen Marije M E
Department of Pediatric Neurology, Antwerp University Hospital, Edegem, Belgium.
Department of Pediatrics, Antwerp University Hospital, Edegem, Belgium.
Front Neurol. 2021 Apr 22;12:617813. doi: 10.3389/fneur.2021.617813. eCollection 2021.
Cerebral palsy (CP) is a non-progressive neurodevelopmental disorder characterized by motor impairments, often accompanied by co-morbidities such as intellectual disability, epilepsy, visual and hearing impairment and speech and language deficits. Despite the established role of hypoxic-ischemic injury in some CP cases, several studies suggest that birth asphyxia is actually an uncommon cause, accounting for <10% of CP cases. For children with CP in the absence of traditional risk factors, a genetic basis to their condition is increasingly suspected. Several recent studies indeed confirm copy number variants and single gene mutations with large genetic heterogeneity as an etiology in children with CP. Here, we report three patients with spastic cerebral palsy and a genetically confirmed diagnosis of Aicardi-Goutières syndrome (AGS), with highly variable phenotypes ranging from clinically suggestive to non-specific symptomatology. Our findings suggest that AGS may be a rather common cause of CP, that frequently remains undiagnosed without additional genetic testing, as in only one case a clinical suspicion of AGS was raised. Our data show that a diagnosis of AGS must be considered in cases with spastic CP, even in the absence of characteristic brain abnormalities. Importantly, a genetic diagnosis of AGS may have significant therapeutic consequences, as targeted therapies are being developed for type 1 interferonopathies, the group of diseases to which AGS belongs. Our findings demonstrate the importance of next generation sequencing in CP patients without an identifiable cause, since targeted diagnostic testing is hampered by the often non-specific presentation.
脑瘫（CP）是一种非进行性神经发育障碍，其特征为运动功能受损，常伴有智力残疾、癫痫、视觉和听觉障碍以及言语和语言缺陷等合并症。尽管缺氧缺血性损伤在某些脑瘫病例中已明确发挥作用，但多项研究表明，出生窒息实际上是一种罕见病因，在脑瘫病例中占比不到10%。对于没有传统风险因素的脑瘫患儿，人们越来越怀疑其病情存在遗传基础。最近的几项研究确实证实，拷贝数变异和具有高度遗传异质性的单基因突变是脑瘫患儿的病因。在此，我们报告了三名痉挛型脑瘫患者，经基因检测确诊为艾卡迪-古铁雷斯综合征（AGS），其表型高度可变，从临床提示性症状到非特异性症状都有。我们的研究结果表明，AGS可能是脑瘫的一个相当常见的病因，如果不进行额外的基因检测，往往无法诊断，因为只有一例病例引发了对AGS的临床怀疑。我们的数据表明，即使没有特征性脑异常，对于痉挛型脑瘫病例也必须考虑AGS的诊断。重要的是，AGS的基因诊断可能会产生重大的治疗后果，因为针对1型干扰素病（AGS所属的疾病组）正在开发靶向治疗方法。我们的研究结果证明了下一代测序在病因不明的脑瘫患者中的重要性，因为靶向诊断检测常常受到非特异性表现的阻碍。
