Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, India.
Morriston Hospital, SBUHB, Swansea, UK.
J Neuromuscul Dis. 2024;11(5):969-979. doi: 10.3233/JND-230172.
Nuclear envelopathies occur due to structural and/or functional defects in various nuclear envelope proteins such as lamin A/C and lamin related proteins. This study is the first report on the phenotype-genotype patterns of nuclear envelopathy-related muscular dystrophies from India.
In this retrospective study, we have described patients with genetically confirmed muscular dystrophy associated with nuclear envelopathy. Data on clinical, laboratory findings and muscle MRI were collected.
Sixteen patients were included with median age at onset of 3 years (range: 1 month - 17 years). Three genes were involved: LMNA (11, 68.75%), EMD (4, 25%) and SYNE1 (1, 6.25%). The 11 patients with LMNA variants were Congenital muscular dystrophy (MDCL)=4, Limb Girdle Muscular Dystrophy (LGMD1B)=4 and Emery-Dreifuss Muscular Dystrophy (EDMD2)=3. On muscle biopsy, one patient from each laminopathy phenotype (n = 3) revealed focal perivascular inflammatory infiltrate. Other notable features were ophthalmoparesis in one and facial weakness in one. None had cardiac involvement. Patients with EDMD1 had both upper (UL) and lower limb (LL) proximo-distal weakness. Cardiac rhythm disturbances such as sick sinus syndrome and atrial arrhythmias were noted in two patients with EDMD1. Only one patient with variant c.654_658dup (EMD) lost ambulation in the 3rd decade, 18 years after disease onset. Two had finger contractures with EMD and SYNE1 variants respectively. All patients with LMNA and SYNE1 variants were ambulant at the time of evaluation. Mean duration of illness (years) was 11.6±13 (MDCL), 3.2±1.0 (EDMD2), 10.4±12.8 (LGMD1B), 11.8±8.4 (EDMD1) and 3 (EDMD4). One patient had a novel SYNE1 mutation (c.22472dupA, exon 123) and presented with UL phenotype and prominent finger and wrist contractures.
The salient features included ophthalmoparesis and facial weakness in LMNA, prominent finger contractures in EMD and SYNE1 and upper limb phenotype with the novel pathogenic variant in SYNE1.
核纤层病是由于各种核纤层蛋白（如核纤层蛋白 A/C 和核纤层相关蛋白）的结构和/或功能缺陷引起的。本研究是印度首例核纤层病相关肌营养不良症表型-基因型模式的报告。
在这项回顾性研究中，我们描述了经基因证实的与核纤层病相关的肌营养不良症患者。收集了临床、实验室检查和肌肉 MRI 的数据。
共纳入 16 例患者，发病中位年龄为 3 岁（范围：1 个月-17 岁）。涉及 3 个基因：LMNA（11 例，68.75%）、EMD（4 例，25%）和 SYNE1（1 例，6.25%）。11 例 LMNA 变异患者中，先天性肌营养不良症（MDCL）=4 例，肢带型肌营养不良症（LGMD1B）=4 例，Emery-Dreifuss 肌营养不良症（EDMD2）=3 例。肌肉活检显示，每种核纤层病表型（n=3）各有 1 例患者存在局灶性血管周围炎性浸润。其他值得注意的特征是 1 例眼肌瘫痪和 1 例面部无力。无心脏受累。EDMD1 患者均有上下肢远近端无力。2 例 EDMD1 患者出现窦性心动过缓和房性心律失常等心律失常。仅 1 例携带 c.654_658dup（EMD）变异的患者在发病 18 年后的第 3 个十年丧失了行走能力。2 例 EMD 和 SYNE1 变异患者分别有手指挛缩。所有 LMNA 和 SYNE1 变异患者在评估时均可行走。疾病平均病程（年）为 11.6±13（MDCL）、3.2±1.0（EDMD2）、10.4±12.8（LGMD1B）、11.8±8.4（EDMD1）和 3（EDMD4）。1 例患者携带新型 SYNE1 突变（c.22472dupA，外显子 123），表现为 UL 表型和明显的手指和腕关节挛缩。
突出的特征包括 LMNA 的眼肌瘫痪和面部无力、EMD 和 SYNE1 的明显手指挛缩以及新型致病变异的 SYNE1 的上肢表型。
