Genetic Disorders Featuring Neurological Implications and Manifestations: A Comprehensive Review

Neurological disorders, fundamentally characterized by intricate genetic etiologies, present with a myriad of pathophysiological features and variable progression trajectories. This comprehensive review delves into the molecular genetics and proteinopathies associated with pivotal neurological disorders, namely Huntington’s disease, Alzheimer’s disease, Multiple Sclerosis (MS), Duchenne Muscular Dystrophy (DMD), Tay-Sachs disease, and Fragile X syndrome. Huntington’s disease, precipitated by pathogenic expansions in the HTT gene, is typified by relentless motor deterioration coupled with cognitive regression. Alzheimer’s disease, distinguished by neurofibrillary tau tangles and extracellular amyloid-beta plaques, predominantly impairs cognitive faculties and memory, with clinical manifestation typically commencing post-60 years of age. Multiple Sclerosis, an autoimmune demyelinating disorder, results in cumulative neurodegeneration, presenting during early adulthood with episodic relapses and progressive neurological disability. Duchenne Muscular Dystrophy, an X-linked recessive disorder, induces catastrophic muscular atrophy due to dystrophin deficiency, while Tay-Sachs disease, attributable to a deficiency in the enzyme hexosaminidase A, leads to swift neurodegenerative decline during infancy. Fragile X syndrome, underpinned by trinucleotide repeat expansions in the FMR1 gene, precipitates profound cognitive and developmental impairments. This review synthesizes cutting-edge research on the pathological roles of proteins such as huntingtin in Huntington’s disease, tau and amyloid-beta in Alzheimer’s, myelin basic proteins in MS, dystrophin in DMD, and β-hexosaminidase in Tay-Sachs, underscoring their critical contributions to disease pathogenesis and highlighting their potential as therapeutic targets. Furthermore, recent strides in molecular diagnostics, particularly in DNA-based predictive testing, alongside novel therapeutic strategies, offer a promising horizon for enhanced clinical management and a deeper understanding of these disorders. This review advocates for sustained research efforts into gene-protein interactions, the role of environmental modifiers, and the development of precision therapies aimed at ameliorating patient outcomes and elevating quality of life.