Journal of Down Syndrome & Chromosome Abnormalities
Open Access

Mitochondrial and Chromosomal Aberrations in Down Syndrome (Trisomy 21) Patients Leading to Diseases

Vinith Sharma^{* *}Correspondence: Vinith Sharma, Department of Medical Genetics, King George's Medical University (KGMU), Lucknow, India, Email:

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Description

Down syndrome also known as trisomy 21 is one of the most prevalent chromosomal abnormalities affecting approximately 1 in 700 live births globally. It is characterized by the presence of an extra copy of chromosome 21 leading to a variety of physical and intellectual disabilities. Beyond the well-known chromosomal anomaly recent studies has decoded on additional molecular and cellular abnormalities particularly involving mitochondria and chromosomal aberrations which significantly impact the health outcomes of individuals with Down syndrome. The perspective explores the complex relationship between mitochondrial dysfunction, chromosomal aberrations and the resultant diseases observed in Down syndrome patients.

The trademark of Down syndrome is the presence of an additional copy of chromosome 21 either as a result of nondisjunction during meiosis (95% of cases) or translocation (4% of cases). This extra genetic material disrupts normal cellular processes and gives rise to the characteristic features associated with the syndrome such as intellectual disability, distinctive facial features and congenital heart defects.

The triplication of chromosome 21 genes alters gene dosage across the genome affecting the expression of genes involved in various biological pathways. One notable consequence is dysregulation of developmental processes which underlies many of the physical abnormalities seen in individuals with Down syndrome. For instance overexpression of genes like DYRK1A can disrupt neurodevelopmental pathways contributing to cognitive impairment.

Mitochondrial dysfunction in Down syndrome

In addition to chromosomal abnormalities mitochondrial dysfunction has emerged as a significant factor contributing to the phenotype and health outcomes of individuals with Down syndrome. Mitochondria are essential organelles responsible for energy production (ATP synthesis) regulation of cell metabolism and apoptosis. Several lines of evidence suggest that mitochondria in Down syndrome exhibit structural and functional abnormalities:

Structural abnormalities: Studies have reported alterations in mitochondrial morphology and size in cells from individuals with Down syndrome. These structural changes may impair mitochondrial function and compromise cellular energy metabolism.

Functional impairments: Mitochondrial function in Down syndrome is often compromised leading to reduced ATP production and increased oxidative stress. Mitochondria from individuals with Down syndrome show decreased respiratory chain complex activity, impaired electron transport chain function and elevated production of Reactive Oxygen Species (ROS). This oxidative stress contributes to cellular damage and accelerates aging processes observed in Down syndrome individuals.

Implications for disease pathogenesis: The interaction between mitochondrial dysfunction and chromosomal abnormalities in Down syndrome contributes to a spectrum of health conditions observed in affected individuals.

Molecular and cellular abnormalities

Here are some key disease manifestations associated with these molecular and cellular abnormalities:

Neurological disorders: Cognitive impairment and early-onset Alzheimer's disease are common in individuals with Down syndrome. Mitochondrial dysfunction and oxidative stress play a critical role in the neurodegenerative processes observed in these conditions.

Cardiovascular abnormalities: Congenital heart defects are common in Down syndrome and are linked to altered gene expression and developmental abnormalities due to trisomy 21. Mitochondrial dysfunction may increase cardiovascular complications through oxidative damage and impaired energy metabolism in cardiac tissues.

Immune dysfunction: Down syndrome individuals often exhibit immune system dysregulation including increased susceptibility to infections and autoimmune disorders. Mitochondrial dysfunction may impair immune cell function contributing to these vulnerabilities.

Endocrine disorders: Thyroid dysfunction and insulin resistance are prevalent in Down syndrome. Mitochondrial dysfunction can disrupt hormonal signaling pathways increases endocrine abnormalities observed in affected individuals.

Therapeutic implications

Understanding the role of mitochondrial dysfunction and chromosomal aberrations in disease pathogenesis holds capability for developing targeted therapeutic interventions for Down syndrome. Potential therapeutic strategies include:

Mitochondrial targeted therapies: Mitochondria targeted antioxidants and compounds that improve mitochondrial function could mitigate oxidative stress and enhance cellular energy metabolism in Down syndrome.

Genetic interventions: Gene therapy approaches aimed at modulating gene dosage or correcting specific chromosomal abnormalities associated with Down syndrome hold potential for ameliorating disease phenotypes.

Nutritional interventions: Dietary supplements and interventions aimed at optimizing mitochondrial function such as coenzyme Q10 and antioxidants may benefit individuals with Down syndrome by reducing oxidative stress and supporting cellular health.

The study of mitochondrial and chromosomal aberrations in Down syndrome provides important insights into the complex etiology of the syndrome and its associated health outcomes. While trisomy 21 leads to widespread gene dysregulation and developmental abnormalities mitochondrial dysfunction increases cellular dysfunction and contributes to the spectrum of diseases observed in affected individuals. Further studies into the molecular mechanisms underlying these abnormalities is essential for developing targeted therapies that address the specific challenges faced by individuals with Down syndrome ultimately improving their quality of life and health outcomes.