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Digeorge Syndrome

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Description: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a genetic disorder caused by the deletion of a small segment of chromosome 22, leading to a range of developmental issues affecting the heart, immune system, and facial features.
Type: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is typically caused by a deletion of a small segment of chromosome 22. The type of genetic transmission is usually autosomal dominant. This means that only one copy of the altered gene is sufficient to cause the disorder. In most cases, this deletion occurs as a random event during the formation of reproductive cells or in early fetal development, but it can also be inherited from an affected parent.
Signs And Symptoms: The features of this syndrome vary widely, even among members of the same family, and affect many parts of the body. Characteristic signs and symptoms may include birth defects such as congenital heart disease, defects in the palate, most commonly related to neuromuscular problems with closure (velopharyngeal insufficiency), learning disabilities, mild differences in facial features, and recurrent infections. Infections are common in children due to problems with the immune system's T cell-mediated response that in some patients is due to an absent or hypoplastic thymus. DiGeorge syndrome may be first spotted when an affected newborn has heart defects or convulsions from hypocalcemia due to malfunctioning parathyroid glands and low levels of parathyroid hormone (parathormone).Affected individuals may also have other kinds of birth defects including kidney abnormalities and significant feeding difficulties as babies. Gastrointestinal issues are also very common in this patient population. Digestive motility issues may result in constipation. Disorders such as hypothyroidism and hypoparathyroidism or thrombocytopenia (low platelet levels), and psychiatric illnesses are common late-occurring features.Microdeletions in chromosomal region 22q11.2 are associated with a 20 to 30-fold increased risk of schizophrenia. Studies provide various rates of 22q11.2DS in schizophrenia, ranging from 0.5 to 2.0% and averaging about 1.0%, compared with the overall estimated 0.025% risk of the 22q11.2DS in the general population.Salient features can be summarized using the mnemonic CATCH-22 to describe 22q11.2DS, with the 22 signifying the chromosomal abnormality is found on the 22nd chromosome, as below:
Cardiac abnormality (commonly interrupted aortic arch, truncus arteriosus and tetralogy of Fallot)
Abnormal facies (Hypertelorism, short down slanting palpebral fissures, tubular nose with anteverted nostrils, short philtrum, carp mouth, mandibular hypoplasia, cleft palate)
Thymic aplasia or hypoplasia
Cleft palate
Hypocalcemia/hypoparathyroidism early in lifeIndividuals can have many possible features, ranging in number of associated features and from the mild to the very serious. Symptoms shown to be common include:

This syndrome is characterized by incomplete penetrance. Therefore, there is a marked variability in clinical expression between the different patients. This often makes early diagnosis difficult.
Prognosis: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, has a variable prognosis that depends largely on the severity of the symptoms and associated health issues.

Prognosis:
- **Mild cases**: Individuals may lead relatively normal lives with proper medical care and support.
- **Severe cases**: Can be associated with significant health problems such as heart defects, immune system deficiencies, and developmental delays, which may impact life expectancy and quality of life.
- **Long-term management**: Regular follow-ups and interventions can improve outcomes. Early diagnosis and treatment are key to managing the condition effectively.

Overall, the prognosis varies widely based on individual circumstances, and multidisciplinary care is often required.
Onset: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, typically manifests in infancy or early childhood. Symptoms can vary widely but often present by early childhood, especially since some critical symptoms, such as congenital heart defects, immune deficiencies due to thymus gland issues, and developmental delays, are present from birth or early infancy. The onset of specific symptoms can range, but many key features are identifiable in the first few months to years of life.
Prevalence: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, occurs in approximately 1 in 4,000 live births.
Epidemiology: DiGeorge syndrome is estimated to affect between one in 2000 and one in 4000 live births. This estimate is based on major birth defects and may be an underestimate, because some individuals with the deletion have few symptoms and may not have been formally diagnosed. It is one of the most common causes of intellectual disability due to a genetic deletion syndrome.The number of people affected has been expected to rise because of multiple reasons: (1) surgical and medical advances, an increasing number of people are surviving heart defects associated with the syndrome. These individuals are in turn having children. The chances of a person with DiGeorge syndrome having an affected child is 50% for each pregnancy; (2) Parents who have affected children, but who were unaware of their own genetic conditions, are now being diagnosed as genetic testing become available; (3) Molecular genetics techniques such as FISH (fluorescence in situ hybridization) have limitations and have not been able to detect all 22q11.2 deletions. Newer technologies have been able to detect these atypical deletions.
Intractability: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, varies widely in its severity and symptoms. While some aspects of the condition can be managed with medical interventions, such as surgery for heart defects or calcium supplementation for hypocalcemia, the syndrome itself is not curable. Comprehensive management involving multiple specialists can improve quality of life and outcomes, but some challenges associated with the syndrome may persist throughout an individual's life.
Disease Severity: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, can vary widely in severity. The condition can manifest with a range of symptoms, from mild to potentially life-threatening complications. Common issues include congenital heart defects, immune system deficiencies, palate abnormalities, developmental delays, and behavioral problems. Each individual's experience with the syndrome can differ significantly.
Healthcare Professionals: Disease Ontology ID - DOID:11198
Pathophysiology: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a disorder caused by a deletion in a small segment of chromosome 22. The pathophysiology primarily involves defects in the development of the third and fourth pharyngeal pouches during embryogenesis. This disruption affects the thymus, parathyroid glands, and portions of the heart and great vessels, leading to a range of clinical manifestations including immunodeficiency (due to thymic hypoplasia or aplasia), hypocalcemia (due to parathyroid hypoplasia), and congenital heart defects (like conotruncal anomalies). Additionally, there can be facial dysmorphisms and developmental delays.
Carrier Status: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is caused by a deletion on chromosome 22. Carrier status is not typically applicable in the traditional sense, as it is usually a de novo (new) deletion, although it can be inherited. Parents of an affected child can undergo genetic testing to determine if they carry the deletion.
Mechanism: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is primarily caused by a deletion of a small segment of chromosome 22 at the q11.2 region. The resulting haploinsufficiency, where one copy of the gene is insufficient to carry out its normal functions, leads to multiple developmental issues.

The molecular mechanisms involve the deletion of several genes in the 22q11.2 region, with the TBX1 gene being a significant contributor. TBX1 encodes a T-box transcription factor important for the development of the pharyngeal arches, which give rise to structures such as the thymus, heart, and parathyroid glands. Loss of TBX1 disrupts normal signaling pathways and transcriptional regulation crucial for the development of these structures, leading to the phenotypic manifestations of the syndrome. Other genes in the deleted region may also contribute to the diversity and variability of clinical symptoms observed in affected individuals.
Treatment: No cure is known for DiGeorge syndrome. Certain individual features are treatable using standard treatments. The key is to identify each of the associated features and manage each using the best available treatments.For example, in children, it is important that the immune problems are identified early, as special precautions are required regarding blood transfusion and immunization with live vaccines.Thymus transplantation can be used to address absence of the thymus in the rare, so-called "complete" DiGeorge syndrome. Bacterial infections are treated with antibiotics. Cardiac surgery is often required for congenital heart abnormalities. Hypoparathyroidism causing hypocalcaemia often requires lifelong vitamin D and calcium supplements. Specialty clinics that provide multi-system care allow for individuals with DiGeorge syndrome to be evaluated for all of their health needs and allow for careful monitoring of the patients. An example of this type of system is the 22q Deletion Clinic at SickKids Hospital in Toronto, Canada, which provides children with 22q11 deletion syndrome ongoing support, medical care and information from a team of health care workers.Metirosine (methyltyrosine) is used as an off-label treatment for DiGeorge syndrome.
Compassionate Use Treatment: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a disorder caused by the deletion of a small segment of chromosome 22. Treatment typically involves managing the specific symptoms and health problems the patient experiences. Since it is a genetic disorder, there is no cure, but supportive treatments are used.

For compassionate use treatment, off-label, or experimental approaches, here are some avenues being explored:

1. **Thymus Transplantation**: For patients with profound T-cell deficiency, thymus transplantation has been used experimentally to reconstitute functional immunity.

2. **Gene Therapy**: Experimental gene therapy is being studied, though it is in very early stages, aiming to correct the genetic defects causing the syndrome.

3. **Hematopoietic Stem Cell Transplantation (HSCT)**: This is considered in certain cases, especially in severe immune dysfunction, although it is not universally adopted and is done under specific situations that may involve compassionate use scenarios.

4. **Off-label Use of Medications**: Certain medications may be used off-label to manage symptoms, such as antipsychotic drugs for psychiatric symptoms, or specific cardiac medications for heart defects associated with the syndrome.

It is crucial to consult with healthcare providers who specialize in genetic and immunological diseases for the latest and most appropriate treatments under experimental or compassionate use protocols.
Lifestyle Recommendations: Lifestyle recommendations for individuals with DiGeorge Syndrome (22q11.2 deletion syndrome) often revolve around managing the various physical and developmental challenges associated with the condition. Key aspects include:

1. **Medical Management**: Regular check-ups with healthcare providers to monitor and address heart defects, immune system issues, and other physical health concerns.

2. **Nutritional Support**: Balanced diet and specific nutritional interventions if feeding difficulties or gastrointestinal issues are present.

3. **Developmental Therapies**: Engagement in speech, occupational, and physical therapies to support developmental delays and learning difficulties.

4. **Educational Support**: Tailored educational programs or special education services to accommodate learning disabilities and cognitive challenges.

5. **Mental Health Care**: Access to mental health services to manage anxiety, depression, and other psychological challenges.

6. **Social Support**: Involvement in support groups and community resources for social integration and family support.

7. **Exercise**: Regular, appropriate physical activity to maintain overall health and well-being.

Adherence to these recommendations can help improve the quality of life for individuals with DiGeorge Syndrome.
Medication: No specific medication cures DiGeorge syndrome (22q11.2 deletion syndrome). Treatment focuses on addressing the individual symptoms and may include calcium and vitamin D supplements for hypocalcemia, antipsychotics or antidepressants for psychiatric symptoms, and antibiotics for recurrent infections. Management often requires a multidisciplinary approach including cardiologists, immunologists, endocrinologists, and other specialists.
Repurposable Drugs: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is primarily managed through symptomatic treatment tailored to the individual's specific issues. Repurposable drugs could include those that address common symptoms or complications of the syndrome, such as antipsychotic medications for psychiatric symptoms or calcium supplements for hypocalcemia. However, it's essential to consult a healthcare provider to determine the most appropriate treatment based on the patient's unique presentation.
Metabolites: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a disorder caused by the deletion of a small segment of chromosome 22. This condition can result in a wide range of symptoms and can affect multiple systems in the body. However, metabolites specifically associated with DiGeorge syndrome in a definitive, characteristic sense are not well-documented. The condition is typically identified through genetic testing rather than metabolic markers.

Common features of DiGeorge syndrome include congenital heart defects, palatal abnormalities, feeding difficulties, immune deficiencies, and developmental delays. The diagnosis is usually confirmed through techniques such as fluorescence in situ hybridization (FISH) or comparative genomic hybridization (CGH) to detect the chromosomal deletion.

Metabolic profiling is not a standard diagnostic tool for DiGeorge syndrome, and specific metabolites associated directly with the disorder are generally not used to diagnose or monitor it. Instead, clinical management focuses on the specific medical, developmental, and psychological needs of the individual.

If you need more detailed information about specific aspects of DiGeorge syndrome or have other questions related to its characteristics and management, feel free to ask.
Nutraceuticals: Nutraceuticals, which are food-derived products that offer health benefits in addition to their basic nutritional value, do not have specific established roles in the management or treatment of DiGeorge syndrome. Management typically involves addressing the symptoms and complications, which can include immune deficiencies, heart defects, and calcium metabolism abnormalities. Appropriate medical and nutritional management should be determined by healthcare professionals based on the individual's specific needs.
Peptides: DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a disorder caused by a deletion in a segment of chromosome 22. This syndrome affects multiple systems in the body and can lead to a wide range of health issues, including heart defects, immune system abnormalities, cleft palate, and learning disabilities. The connection to peptides and nanotechnologies (nan.) in relation to DiGeorge syndrome is not commonly covered as of now. Current treatments do not typically involve peptides or nanotechnologies directly, but future research may explore these areas for potential therapeutic strategies.