Moreno Cristiane Araujo Martins, Artilheiro Mariana Cunha, Fonseca Alulin Tacio Quadros Santos Monteiro, Camelo Clara Gontijo, de Medeiros Gisele Chagas, Sassi Fernanda Chiarion, de Andrade Claudia Regina Furquim, Donkervoort Sandra, Silva Andre Macedo Serafim, Dalfior-Junior Luiz, Abath-Neto Osorio Lopes, Reed Umbertina Conti, Bönnemann Carsten, Zanoteli Edmar
Department of Neurology (C.A.M.M., M.C.A., A.T.Q.S.M.F., C.G.C., A.M.S.S., U.C.R., E.Z.), School of Medicine, Universidade de São Paulo (FMUSP), Brazil; Department of Physical Therapy (G.C.M., F.C.S., C.R.F.A.), Speech Language and Hearing Science Adn Occupational Therapy, School of Medicine, Universidade de São Paulo (FMUSP), Brazil; Neuromuscular and Neurogenetic Disorders of Childhood Section (S.D., C.B.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Department of Neurology, Hospital Santa Marcelina (L.D.J.), São Paulo, Brazil; and Department of Pathology (O.L.A.-N.), Division of Neuropathology, University of Pittsburgh Medical Center, Pittsburgh, PA.
Neurol Genet. 2023 Jan 25;9(1):e200056. doi: 10.1212/NXG.0000000000200056. eCollection 2023 Feb.
Nemaline myopathy (NM) is a genetically heterogeneous inherited myopathy related with at least 12 genes, whereas pathogenic variants in gene are the most common genetic cause. The clinical spectrum of NM caused by NEB pathogenic variants (NM-) is very broad, ranging from mild to severe presentations manifesting with generalized weakness, as well as respiratory and bulbar involvement. There is currently not enough data regarding the progression of the disease. In this study, we present a genotypic and phenotypic spectrum of 33 patients with NM caused by NEB variants (NM-) classified according to age groups and the use of ventilatory support. We focused on interventional support, genotype-phenotype correlation, and association between respiratory, bulbar, and motor systems in groups of patients stratified by age and by the use of ventilatory support (VS).
Clinical and genetic data from patients with NM-NEB followed up in one specialized center were collected through regular consultations. Patients were evaluated regarding motor, bulbar, and respiratory functions.
Thirty-three patients with NM-NEB were evaluated consisting of 15 females and 18 males with an average age of 18 (±12) years and a median of 17 (±11) years. 32% of patients with NM-NEB used a G tube, 35% were not able to walk without support, and 55% needed VS. Scoliosis and dysphagia were more common among patients who used VS. Described for the first time, half of the patients presented tongue atrophy in a triple furrow pattern, and the presence of the atrophy was associated with dysphagia. Comparing the patients grouped by age, we found that, proportionally, older patients had more scoliosis and respiratory dysfunction than younger groups, suggesting the progression of the disease in these domains. In addition to that, we showed that VS use was associated with scoliosis and dysphagia.
NM-NEB is a very debilitating disease. There is an association between scoliosis and respiratory dysfunction while patients using VS have more often scoliosis than the no-VS group. Triple furrow tongue atrophy is a novel and frequent finding, which is directly associated with dysphagia. Grouping patients by age suggested disease stability in motor and swallow function, but a progression in respiratory dysfunction and skeletal deformities. All observations are relevant in the management care of patients with NM.
杆状体肌病（NM）是一种遗传异质性遗传性肌病，与至少12个基因相关，而该基因中的致病变异是最常见的遗传病因。由NEB致病变异引起的NM（NM-NEB）的临床谱非常广泛，从轻度到重度表现，包括全身无力以及呼吸和延髓受累。目前关于该疾病进展的数据不足。在本研究中，我们呈现了33例由NEB变异引起的NM患者（NM-NEB）的基因型和表型谱，这些患者根据年龄组和通气支持的使用情况进行分类。我们关注干预支持、基因型-表型相关性以及在按年龄和通气支持（VS）使用情况分层的患者组中呼吸、延髓和运动系统之间的关联。
通过定期会诊收集在一个专业中心随访的NM-NEB患者的临床和遗传数据。对患者的运动、延髓和呼吸功能进行评估。
对33例NM-NEB患者进行了评估，其中15例女性和18例男性，平均年龄为18（±12）岁，中位数为17（±11）岁。32%的NM-NEB患者使用胃造口管，35%的患者在无支撑的情况下无法行走，55%的患者需要通气支持。脊柱侧弯和吞咽困难在使用通气支持的患者中更为常见。首次描述，一半的患者出现呈三条沟纹状的舌萎缩，且萎缩的存在与吞咽困难相关。比较按年龄分组的患者，我们发现，按比例而言，老年患者比年轻组有更多的脊柱侧弯和呼吸功能障碍，提示这些方面疾病的进展。除此之外，我们表明通气支持的使用与脊柱侧弯和吞咽困难相关。
NM-NEB是一种非常使人衰弱的疾病。脊柱侧弯与呼吸功能障碍之间存在关联，使用通气支持的患者比未使用通气支持的组更常出现脊柱侧弯。三条沟纹状舌萎缩是一个新的且常见的发现，它与吞咽困难直接相关。按年龄对患者进行分组表明运动和吞咽功能方面疾病稳定，但呼吸功能障碍和骨骼畸形有进展。所有这些观察结果在NM患者的管理护理中都具有相关性。
