Rive Le Gouard Nicolas, G Bah Maissa, Coarelli Giulia, Heinzmann Anna, Fauret Anne-Laure, de Sainte-Agathe Jean-Madeleine, Cazeneuve Cécile, Gerasimenko Anna, Gras Domitille, Capri Yline, Renaud Mathilde, Brais Bernard, Grenenko Cecile, Masurel Alice, Berquin Patrick, Jobic Florence, Métreau Julia, Deiva Kumaran, Afenjar Alexandra, Gravrand Victor, Lannuzel Annie, Anheim Mathieu, Geis Tobias, Hehr Ute, Madan Cohen Jennifer, Desnous Béatrice, J A Kievit Anneke, Bahi-Buisson Nadia, Rodriguez Diana, Renaldo Florence, Cances Claude, Devos David, Angelini Chloé, Goizet Cyril, Ewenczyk Claire, Durr Alexandra, Mignot Cyril
Département de Génétique médicale, Hôpital Armand Trousseau et Groupe Hospitalier Pitié-Salpêtrière, APHP Sorbonne Université, Paris, France.
APHP, Urgences Pédiatriques, CHU Robert Debré, Paris, France.
Eur J Neurol. 2025 Aug;32(8):e70314. doi: 10.1111/ene.70314.
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurological disease usually described in adults. Expanded CAG repeats in the ATXN2 gene can lead to pediatric onset. This study aims to describe the natural history of SCA2 in children.
We analyzed clinical and genetic data from 22 children with SCA2 across 17 institutions and compared them to 20 previously reported cases.
The phenotype of pediatric SCA2 can be divided into two distinct groups based on CAG repeat size and age. In the infantile group (n = 9), developmental delay and seizures were prominent features, along with cerebellar and cerebral atrophy. In the juvenile group (n = 13), the disease was a cerebellar degeneration similar to adults. A threshold of 88 ± 4 CAG repeats distinguished the infantile group from the juvenile group. Pediatric SCA2 type was independent of parental origin; SCA2 was maternally inherited in 22%, including three infantile presentations.
This large cohort of pediatric SCA2 disease provides the first comprehensive description of its characteristics, which differ from those of SCA7. Indeed, the phenotypic spectrum of SCA7 in children is continuous, while that of SCA2 is bimodal. Although pediatric SCA2 can be difficult to diagnose by genome-wide sequencing, it is a recognizable disease that can be easily diagnosed with a targeted study of the number of CAGs in ATXN2. Genetic counseling for families should consider the significant proportion of maternal transmission.
2型脊髓小脑共济失调（SCA2）是一种常染色体显性神经疾病，通常在成人中出现。ATXN2基因中CAG重复序列的扩增可导致儿童期发病。本研究旨在描述儿童SCA2的自然病史。
我们分析了来自17个机构的22例儿童SCA2患者的临床和基因数据，并将其与之前报道的20例病例进行比较。
儿童SCA2的表型可根据CAG重复序列长度和年龄分为两个不同的组。在婴儿组（n = 9）中，发育迟缓、癫痫发作是突出特征，同时伴有小脑和大脑萎缩。在青少年组（n = 13）中，该疾病表现为与成人相似的小脑变性。88 ± 4个CAG重复序列的阈值区分了婴儿组和青少年组。儿童SCA2类型与亲本来源无关；22%的病例为母系遗传，其中包括3例婴儿期发病。
这一大型儿童SCA2疾病队列首次全面描述了其特征，这些特征与SCA7不同。事实上，儿童SCA7的表型谱是连续的，而SCA2的表型谱是双峰的。尽管通过全基因组测序难以诊断儿童SCA2，但它是一种可识别的疾病，通过对ATXN2中CAG数量的靶向研究可以轻松诊断。对家庭的遗传咨询应考虑母系遗传的显著比例。
