Scientific Institute IRCCS. "E. Medea", Scientific Direction, 23842 Bosisio Parini, Italy.
Associazione "La Nostra Famiglia", IRCCS "E. Medea", Scientific Hospital for Neurorehabilitation, Unit for Severe Disabilities in Developmental Age and Young Adults, Developmental Neurology and Neurorehabilitation, 72100 Brindisi, Italy.
Genes (Basel). 2024 Oct 21;15(10):1346. doi: 10.3390/genes15101346.
Inherited pediatric motor neuron diseases (MNDs) are a group of neurodegenerative disorders characterized by the degeneration of motor neurons in the brain and the spinal cord. These diseases can manifest as early as infancy and originate from inherited pathogenic mutations in known genes. Key clinical features of MNDs include muscle weakness, hypotonia, and atrophy due to the degeneration of lower motor neurons or spasticity, hypertonia, and hyperreflexia caused by upper motor neuron dysfunction. The course of the disease varies among individuals and is influenced by the specific subtype.
We performed a non-systematic, narrative clinical review, employing a systematic methodology for the literature search and article selection to delineate the features of hereditary pediatric motor neuron diseases.
The growing availability of advanced molecular testing, such as whole-exome sequencing (WES) and whole-genome sequencing (WGS), has expanded the range of identified genetic factors. These advancements provide insights into the genetic complexity and underlying mechanisms of these disorders. As more MND-related genes are discovered, the accumulating genetic data will help prioritize promising candidate genes for future research. In some cases, targeted treatments based on specific genetic mechanisms have already emerged, underscoring the critical role of early and timely diagnosis in improving patient outcomes. Common MNDs include amyotrophic lateral sclerosis, spinal muscular atrophy, and bulbar spinal muscular atrophy.
This narrative clinical review covers the clinical presentation, genetics, molecular features, and pathophysiology of inherited pediatric MNDs.
遗传性儿童运动神经元病（MND）是一组神经退行性疾病，其特征是大脑和脊髓中的运动神经元退化。这些疾病可能在婴儿期就出现，并由已知基因中的遗传致病性突变引起。MND 的主要临床特征包括由于下运动神经元退化引起的肌肉无力、低张力和萎缩，或由于上运动神经元功能障碍引起的痉挛、高张力和反射亢进。疾病的病程在个体之间有所不同，并受特定亚型的影响。
我们进行了非系统性、叙述性临床综述，采用系统的文献搜索和文章选择方法来描述遗传性儿童运动神经元疾病的特征。
随着全外显子组测序（WES）和全基因组测序（WGS）等先进分子检测技术的不断发展，已鉴定出更多的遗传因素。这些进展为了解这些疾病的遗传复杂性和潜在机制提供了线索。随着更多的 MND 相关基因被发现，不断积累的遗传数据将有助于为未来的研究确定有希望的候选基因。在某些情况下，已经出现了基于特定遗传机制的靶向治疗，这突显了早期和及时诊断在改善患者预后方面的重要性。常见的 MND 包括肌萎缩侧索硬化症、脊髓性肌萎缩症和延髓脊髓性肌萎缩症。
本叙述性临床综述涵盖了遗传性儿童 MND 的临床表现、遗传学、分子特征和病理生理学。
