Congenital myopathies Natural history of a large pediatric cohort
Congenital myopathies Natural history of a large pediatric cohort
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DOI：
10.1212/wnl.0000000000001110
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发表时间：
2015-01-06
期刊：
影响因子：
9.9
通讯作者：
Muntoni, Francesco
中科院分区：
文献类型：
--
作者：
Colombo, Irene;Scoto, Mariacristina;Muntoni, Francesco
目的：评估由不同基因型导致的先天性肌病（CMs）的自然病程。
方法：基于对1984年至2012年间在一家儿科神经肌肉中心随访的125例先天性肌病患者的病例记录回顾进行回顾性横断面研究。
结果：125例中有99例（79.2%）完成了基因鉴定，其中RYR1最常受累（125例中有44例）。76%的患者在新生儿/婴儿期发病。出生时，30.4%的患者需要呼吸支持，25.2%需要鼻胃管喂养。12%的患者死亡，主要在第一年内，与ACTA1、MTM1或KLHL40突变有关。所有RYR1突变的病例均存活，且不需要长期呼吸机支持，包括那些新生儿期发病严重的病例；然而，隐性病例与显性病例相比更可能需要胃造口术（p = 0.0028）。所有患者中有74.1%能够独立行走；62.9%为晚走路者。在能行走的患者中，9%最终依赖轮椅。40%的患者报告有不同程度的脊柱侧凸，其中1/3（能行走和不能行走的）患者需要手术。46.4%的患者存在延髓受累，28.8%的患者需要放置胃造口管（平均年龄2.7岁）。64.1%的患者存在不同程度的呼吸功能障碍；由于呼吸衰竭，这些患者中约一半需要夜间无创通气（平均年龄8.5岁）。
结论：我们描述了一大群先天性肌病患者的长期预后。虽然总体病程稳定，但我们展示了广泛的临床谱，一部分病例存在运动功能恶化。新生儿/婴儿期的严重程度对生存至关重要，明确的基因型 - 表型相关性可能为未来的咨询提供信息。
Objective: To assess the natural history of congenital myopathies (CMs) due to different genotypes.Methods: Retrospective cross-sectional study based on case-note review of 125 patients affected by CM, followed at a single pediatric neuromuscular center, between 1984 and 2012.Results: Genetic characterization was achieved in 99 of 125 cases (79.2%), with RYR1 most frequently implicated (44/125). Neonatal/infantile onset was observed in 76%. At birth, 30.4% required respiratory support, and 25.2% nasogastric feeding. Twelve percent died, mainly within the first year, associated with mutations in ACTA1, MTM1, or KLHL40. All RYR1-mutated cases survived and did not require long-term ventilator support including those with severe neonatal onset; however, recessive cases were more likely to require gastrostomy insertion (p = 0.0028) compared with dominant cases. Independent ambulation was achieved in 74.1% of all patients; 62.9% were late walkers. Among ambulant patients, 9% eventually became wheelchair-dependent. Scoliosis of variable severity was reported in 40%, with 1/3 of (both ambulant and nonambulant) patients requiring surgery. Bulbar involvement was present in 46.4% and required gastrostomy placement in 28.8%(at a mean age of 2.7 years). Respiratory impairment of variable severity was a feature in 64.1%; approximately half of these patients required nocturnal noninvasive ventilation due to respiratory failure (at a mean age of 8.5 years).Conclusions: We describe the long-term outcome of a large cohort of patients with CMs. While overall course is stable, we demonstrate a wide clinical spectrum with motor deterioration in a subset of cases. Severity in the neonatal/infantile period is critical for survival, with clear genotype-phenotype correlations that may inform future counseling.