362P Whole-body MRI reveals common and distinctive muscle involvement in “clinically asymptomatic” female carriers of pathogenic DMD variants

IF 2.7 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders Pub Date : 2024-10-01 DOI:10.1016/j.nmd.2024.07.099

F. Giliberto , A. Vigliano , L. Luce , J. Pastor Rueda , H. Chaves , L. Mesa , M. Carcione , C. Mazzanti , C. Llames Massini , P. Radic , C. Cejas

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引用次数: 0

Abstract

DMD-carriers were traditionally considered asymptomatic given the X-linked recessive inheritance pattern of these diseases. Yet, it has recently been discovered that they exhibit different levels of muscle involvement.

This study aimed to characterize and compare the muscle structure on MRI of DMD-carriers and a control group. Secondly, we pursue a correlation between levels of muscle involvement and clinical manifestations, creatine kinase (CK) levels, DMD molecular alteration and X-chromosome inactivation (XCI) patterns. We enrolled 30 genetically confirmed DMD female carriers and 30 healthy non-carrier controls, BMI and age matched. All individuals underwent whole-body MRI, where semi-quantitative scales were used to assess muscle edema, trophism and fatty infiltration. Neurological examination, Serum CK measurement, DMD genetic screening, and XCI studies were only performed on the DMD-carriers. Statistically significant differences in muscle involvement were observed between DMD-carriers and the control group. Female carriers exhibited muscle affection in 33% of the 48 muscle groups analyzed, while the control group presented only the 10% affected. Most of the DMD-carriers’ implicated muscles showed mild atrophy and mild to moderate fatty infiltration. The muscles more frequently affected were gastrocnemius, gluteus maximus and soleus. No statistical correlation was found between the levels or pattern of muscle involvement on MRI and the neurological examination, CK values, type of genetic variant and XCI patterns. DMD-carriers exhibit frequent and distinctive muscle involvement patterns on MRI, questioning the conception of “asymptomatic” DMD-Carriers. These results, together with findings in other X-linked disorders, lead to a revision of the concept of asymptomatic carriers of X-linked recessive diseases and raise awareness of the need to develop best practice guidelines for the evaluation and management of these females.

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362P 全身核磁共振成像显示，"临床无症状 "的女性致病性 DMD 变体携带者的肌肉普遍受累，且各具特色

鉴于 DMD 的 X 连锁隐性遗传模式，传统上认为 DMD 携带者没有症状。本研究旨在对 DMD 携带者和对照组的肌肉结构进行特征描述和核磁共振成像比较。其次，我们研究了肌肉受累程度与临床表现、肌酸激酶（CK）水平、DMD 分子改变和 X 染色体失活（XCI）模式之间的相关性。我们招募了 30 名经遗传学证实的 DMD 女性携带者和 30 名健康的非携带者对照组（体重指数和年龄匹配）。所有患者均接受了全身核磁共振成像检查，采用半定量量表评估肌肉水肿、萎缩和脂肪浸润。仅对 DMD 携带者进行了神经系统检查、血清 CK 测量、DMD 基因筛查和 XCI 研究。据统计，DMD 携带者与对照组在肌肉受累方面存在明显差异。在分析的 48 组肌肉中，女性携带者有 33% 的肌肉受累，而对照组仅有 10% 的肌肉受累。大多数 DMD 携带者的受累肌肉表现为轻度萎缩和轻度至中度脂肪浸润。最常受影响的肌肉是腓肠肌、臀大肌和比目鱼肌。核磁共振成像显示的肌肉受累程度或模式与神经系统检查、CK 值、基因变异类型和 XCI 模式之间没有统计学关联。DMD 携带者在核磁共振成像上表现出频繁和独特的肌肉受累模式，这对 "无症状 "DMD 携带者的概念提出了质疑。这些结果以及对其他 X 连锁疾病的研究结果促使人们对 X 连锁隐性疾病无症状携带者的概念进行修正，并使人们认识到有必要制定评估和管理这些女性的最佳实践指南。

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来源期刊

Neuromuscular Disorders 医学-临床神经学

CiteScore

4.60

自引率

3.60%

发文量

543

审稿时长

53 days

期刊介绍： This international, multidisciplinary journal covers all aspects of neuromuscular disorders in childhood and adult life (including the muscular dystrophies, spinal muscular atrophies, hereditary neuropathies, congenital myopathies, myasthenias, myotonic syndromes, metabolic myopathies and inflammatory myopathies). The Editors welcome original articles from all areas of the field: • Clinical aspects, such as new clinical entities, case studies of interest, treatment, management and rehabilitation (including biomechanics, orthotic design and surgery). • Basic scientific studies of relevance to the clinical syndromes, including advances in the fields of molecular biology and genetics. • Studies of animal models relevant to the human diseases. The journal is aimed at a wide range of clinicians, pathologists, associated paramedical professionals and clinical and basic scientists with an interest in the study of neuromuscular disorders.