GeneHealth - Your precision medicine

Trisomy 21

Disease Details

Family Health Simplified

Buy Membership

Description: Trisomy 21, also known as Down syndrome, is a genetic disorder caused by the presence of an extra copy of chromosome 21, leading to developmental delays, intellectual disability, and characteristic facial features.
Type: Trisomy 21, also known as Down syndrome, is a chromosomal disorder. The type of genetic transmission is usually non-heritable, occurring due to a random error in cell division called nondisjunction, which results in an extra copy of chromosome 21. In a smaller percentage of cases, it can be due to a heritable form called a Robertsonian translocation.
Signs And Symptoms: Those with Down syndrome nearly always have physical and intellectual disabilities. As adults, their mental abilities are typically similar to those of an 8- or 9-year-old. At the same time, their emotional and social awareness is very high. They can have poor immune function and generally reach developmental milestones at a later age. They have an increased risk of a number of health concerns, such as congenital heart defect, epilepsy, leukemia, and thyroid diseases.
Prognosis: Between 5-15% of children with Down syndrome in Sweden attend regular school. Some graduate from high school; however, most do not. Of those with intellectual disability in the United States who attended high school about 40% graduated. Many learn to read and write and some are able to do paid work. In adulthood about 20% in the United States do paid work in some capacity. In Sweden, however, less than 1% have regular jobs. Many are able to live semi-independently, but they often require help with financial, medical, and legal matters. Those with mosaic Down syndrome usually have better outcomes.Individuals with Down syndrome have a higher risk of early death than the general population. This is most often from heart problems or infections. Following improved medical care, particularly for heart and gastrointestinal problems, the life expectancy has increased. This increase has been from 12 years in 1912, to 25 years in the 1980s, to 50 to 60 years in the developed world in the 2000s. Data collected between the 1985–2003 showed between 4-12% infants with Down syndrome die in the first year of life. The probability of long-term survival is partly determined by the presence of heart problems. From research at the turn of the century, it tracked those with congenital heart problems, showing 60% survived to at least 10 years and 50% survived to at least 30 years of age. The research failed to track further aging beyond 30 years. In those without heart problems, 85% studied survived to at least 10 years and 80% survived to at least 30 years of age. It is estimated that 10% lived to 70 years of age in the early 2000s. Much of this data is outdated and life expectancy has drastically improved with more equitable healthcare and continuous advancement of surgical practice. The National Down Syndrome Society provides information regarding raising a child with Down syndrome.
Onset: Trisomy 21, commonly known as Down syndrome, is a genetic disorder present from birth. The condition is characterized by an extra copy of chromosome 21. Onset is therefore congenital, meaning it is present at birth and the features and symptoms associated with Down syndrome are usually evident in infancy or early childhood.
Prevalence: Trisomy 21, also known as Down syndrome, affects approximately 1 in 700 live births.
Epidemiology: Down syndrome is the most common chromosomal abnormality in humans. Globally, as of 2010, Down syndrome occurs in about 1 per 1,000 births and results in about 17,000 deaths. More children are born with Down syndrome in countries where abortion is not allowed and in countries where pregnancy more commonly occurs at a later age. About 1.4 per 1,000 live births in the United States and 1.1 per 1,000 live births in Norway are affected. In the 1950s, in the United States, it occurred in 2 per 1,000 live births with the decrease since then due to prenatal screening and abortions. The number of pregnancies with Down syndrome is more than two times greater with many spontaneously aborting. It is the cause of 8% of all congenital disorders.Maternal age affects the chances of having a pregnancy with Down syndrome. At age 20, the chance is 1 in 1,441; at age 30, it is 1 in 959; at age 40, it is 1 in 84; and at age 50 it is 1 in 44. Although the probability increases with maternal age, 70% of children with Down syndrome are born to women 35 years of age and younger, because younger people have more children. The father's older age is also a risk factor in women older than 35, but not in women younger than 35, and may partly explain the increase in risk as women age.
Intractability: Trisomy 21, also known as Down syndrome, is a genetic condition caused by an extra copy of chromosome 21. It is not curable, meaning the genetic aspect of the condition cannot be altered. However, it is not entirely intractable in terms of management. Many of the health issues and developmental challenges associated with Down syndrome can be managed through medical care, therapies, and educational support. With appropriate interventions, individuals with Down syndrome can lead fulfilling lives.
Disease Severity: Trisomy 21, also known as Down syndrome, varies in severity. It is characterized by intellectual disability, developmental delays, and distinct facial features. The severity can range from mild to moderate to severe, impacting individuals differently in areas like cognitive ability, physical health, and development.
Healthcare Professionals: Disease Ontology ID - DOID:14250
Pathophysiology: Trisomy 21, also known as Down syndrome, is caused by the presence of an extra copy of chromosome 21. This results from nondisjunction during cell division, leading to three copies of this chromosome instead of the usual two. The extra genetic material disrupts normal development, contributing to the characteristic physical features, intellectual disabilities, and increased risk of certain medical conditions such as congenital heart defects, respiratory and hearing problems, Alzheimer's disease, and leukemia. The specific genes and their interactions on chromosome 21 that lead to these manifestations are still being researched.
Carrier Status: Trisomy 21, commonly known as Down syndrome, is typically not associated with carrier status in the context of autosomal trisomy. Down syndrome usually results from a random error in cell division called nondisjunction, leading to an extra copy of chromosome 21. However, a small percentage of cases (approximately 3-4%) result from a hereditary form known as Robertsonian translocation, where a parent's balanced translocation can increase the risk of having a child with Down syndrome. In such cases, one parent can be a carrier of the translocation without showing symptoms.
Mechanism: The extra genetic material present in Down syndrome results in overexpression of a portion of the 310 genes located on chromosome 21. This overexpression has been estimated at 50%, due to the third copy of the chromosome present. Some research has suggested the Down syndrome critical region is located at bands 21q22.1–q22.3, with this area including genes for the amyloid precursor protein, superoxide dismutase, and likely the ETS2 proto oncogene. Other research, however, has not confirmed these findings. MicroRNAs are also proposed to be involved.The dementia that occurs in Down syndrome is due to an excess of amyloid beta peptide produced in the brain and is similar to Alzheimer's disease, which also involves amyloid beta build-up. Amyloid beta is processed from amyloid precursor protein, the gene for which is located on chromosome 21. Senile plaques and neurofibrillary tangles are present in nearly all by 35 years of age, though dementia may not be present. It is hypothesized that those with Down syndrome lack a normal number of lymphocytes and produce less antibodies which is said to present an increased risk of infection.
Treatment: Trisomy 21, also known as Down syndrome, does not have a cure. Treatment focuses on managing symptoms and supporting development. This often involves a combination of healthcare providers, including pediatricians, cardiologists, speech therapists, occupational therapists, and special education professionals. Early intervention programs and individualized education plans (IEPs) can help optimize developmental outcomes. Regular health check-ups and screenings are crucial to address any associated medical conditions, such as heart defects or thyroid issues.
Compassionate Use Treatment: For Trisomy 21, also known as Down syndrome, there is currently no cure. However, various supportive treatments and interventions are used to improve quality of life and manage associated health issues. These treatments can be categorized into compassionate use treatments, off-label uses, and experimental treatments:

1. **Compassionate Use Treatment:**
- **Medications for Associated Conditions:** Medications not specifically approved for Down syndrome but used to treat co-existing conditions, such as hypothyroidism, hearing loss, and gastrointestinal issues, can be part of compassionate use. These are critical for managing specific health problems that may arise.
- **Nutritional and Metabolic Interventions:** Supplements and dietary modifications may be considered to support overall health, addressing common concerns like immune function and metabolic imbalances.

2. **Off-Label Treatments:**
- **Piracetam:** Although primarily used for cognitive enhancement or to treat myoclonic seizures, some clinicians have explored its use in individuals with Down syndrome to potentially improve cognitive functions, though evidence is limited and inconsistent.
- **Donepezil:** Commonly used for Alzheimer's disease, Donepezil has been used off-label to target cognitive decline in Down syndrome, but its efficacy is still under investigation.
- **Sleep Apnea Treatments:** Continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea is often used off-label in Down syndrome as sleep apnea is common in this population.

3. **Experimental Treatments:**
- **Gene Therapy:** Research is ongoing into potential gene therapies that could address the underlying genetic cause of Down syndrome. These are still largely in the experimental phase and not yet available for general use.
- **Stem Cell Therapy:** Some experimental approaches involve using stem cells to potentially treat or manage various aspects of Down syndrome, though these are not yet proven and are only available in clinical trial settings.
- **Targeted Pharmacological Interventions:** Various drugs that target specific pathways involved in the cognitive symptoms of Down syndrome are in development or early clinical trials. Examples include compounds targeting the DYRK1A gene or the APP gene.

Participation in clinical trials can be an option for some families seeking the latest experimental therapies. Always consult with medical professionals who specialize in Down syndrome for the most personalized and up-to-date therapeutic options.
Lifestyle Recommendations: Trisomy 21, commonly known as Down syndrome, can be managed with specific lifestyle recommendations to enhance overall health and well-being. Here are some key lifestyle recommendations:

1. **Regular Medical Care**: Routine check-ups with healthcare providers are essential to monitor and manage any associated health conditions, such as heart defects, thyroid disorders, and hearing or vision problems.

2. **Balanced Diet**: A nutritious diet rich in fruits, vegetables, whole grains, and lean proteins is important. Consider consulting a dietitian to address any specific dietary needs.

3. **Physical Activity**: Regular physical exercise helps improve cardiovascular health, muscle strength, and overall fitness. Activities should be suitable for the individual's abilities and interests.

4. **Therapies**: Early intervention with physical, occupational, and speech therapy can support developmental milestones. Continuing with these therapies as needed throughout life can help maintain and enhance skills.

5. **Educational Support**: Tailored educational programs and resources can help individuals with Down syndrome achieve academic goals and improve cognitive skills. Special education services may be beneficial.

6. **Social Engagement**: Encouragement of social interactions and participation in community activities can enhance social skills and emotional well-being. Building a support network with peers and others can provide significant benefits.

7. **Sleep Hygiene**: Ensuring a regular sleep schedule and addressing any sleep disorders, such as obstructive sleep apnea, is crucial for overall health.

8. **Mental Health**: Monitoring and supporting mental health is important. Persons with Down syndrome may be at higher risk for certain psychiatric conditions, so staying vigilant and seeking professional help when needed is vital.

9. **Personal Independence**: As much as possible, encourage personal independence in daily activities, while providing support and guidance tailored to individual needs.

10. **Safety Measures**: Due to potential intellectual and developmental delays, ensuring a safe living environment and teaching about safety precautions are important.

These lifestyle recommendations, along with a strong support system, can significantly improve the quality of life for individuals with Down syndrome.
Medication: There is no specific medication to cure or treat Trisomy 21 (Down syndrome). Instead, treatment focuses on managing symptoms and associated health conditions, which may include:

1. Congenital heart defects: Medications may be prescribed to manage symptoms or support heart function, and surgery may be needed.
2. Thyroid issues: Thyroid hormone replacement therapy for hypothyroidism.
3. Gastrointestinal problems: Medications or surgery for conditions like Hirschsprung's disease or gastroesophageal reflux.
4. Sleep apnea: Treatments may include weight management, CPAP therapy, or surgery.
5. Infections: Prompt antibiotic treatment for frequent ear infections or respiratory infections.

Early intervention programs, therapies (physical, occupational, speech), and support from healthcare professionals are essential for managing the diverse needs of individuals with Trisomy 21.
Repurposable Drugs: Repurposable drugs for trisomy 21 (Down syndrome) are limited, but some drugs that have shown potential in research include:

1. **Fluoxetine**: An SSRI that has shown promise in improving cognitive function in animal models.
2. **Eicosapentaenoic Acid (EPA)**: An omega-3 fatty acid that may help with brain inflammation and cognitive function.
3. **Epigallocatechin gallate (EGCG)**: Found in green tea, EGCG has been studied for its potential in improving cognitive function through antioxidant properties.

It's important to consult healthcare professionals before considering any treatment options.
Metabolites: Trisomy 21, also known as Down syndrome, is associated with several metabolic abnormalities. The metabolites of interest in individuals with Down syndrome include:

1. **Amino Acids**: Altered levels of certain amino acids, such as decreased levels of serine and increased levels of cystathionine.
2. **Homocysteine**: Typically, individuals with Down syndrome have lower levels of homocysteine, which is related to folate metabolism.
3. **Oxidative stress markers**: Elevated levels of oxidative stress markers like malondialdehyde (MDA).
4. **Hormones**: Variations in thyroid hormones, often leading to hypothyroidism.
5. **Uric Acid**: Typically elevated uric acid levels.

Analysis of these metabolites can provide insights into the biochemical and physiological changes associated with Down syndrome.
Nutraceuticals: There are no nutraceuticals specifically proven to treat or alter the genetic aspects of trisomy 21 (Down syndrome). While a balanced diet and certain supplements may support overall health, it's important to consult healthcare professionals before starting any new supplements. Research on nanoscale therapeutics for trisomy 21 is in early stages, with no established treatments currently available.
Peptides: Trisomy 21, also known as Down syndrome, is a genetic disorder caused by the presence of an extra copy of chromosome 21. While peptides and nanotechnology are not directly related to the genetic cause of the condition, they may have potential roles in research and treatment.

Peptides: These short chains of amino acids can be involved in various biological functions. Research is exploring the use of peptides to possibly influence pathways that are altered in Down syndrome, such as those related to brain function and development.

Nanotechnology (Nan): This involves manipulating materials at an atomic or molecular scale. In the context of Down syndrome, nanotechnology could be used for targeted drug delivery, diagnostic tools, or even gene editing techniques to address some symptoms or complications associated with the disorder. However, these applications are still largely in the research phase and not yet available as standard treatments.