Digeorge Syndrome (22q11.2 Deletion Syndrome)

DiGeorge syndrome, also called 22q11.2 deletion syndrome, happens when a tiny piece of chromosome 22 is missing. This missing piece can affect how different parts of the body develop.

The name 22q11.2 deletion syndrome groups together several conditions that were once thought to be separate. These conditions include DiGeorge syndrome, velocardiofacial syndrome (this name describes the facial features and heart problems often seen), and other similar issues. While the cause is the same missing genetic material, the specific features and severity of the condition can vary from person to person.

People with 22q11.2 deletion syndrome often have health problems affecting different parts of the body. These can include heart problems, a weaker immune system, a cleft palate (a split in the roof of the mouth), problems with low calcium levels, eye difficulties, and autoimmune disorders (where the body's immune system attacks its own tissues). Other possible issues include hearing loss, differences in bone structure, kidney problems, differences in the genitals, and developmental delays, which can lead to behavioral and emotional challenges.

The specific symptoms and how severe they are differ widely between individuals with 22q11.2 deletion syndrome. However, most people with this condition will need care from specialists in different areas of medicine to manage their health needs.

DiGeorge syndrome affects people in different ways, depending on which parts of their bodies are impacted and how severe the problems are. Some signs are noticeable right after birth, while others might not appear until later in childhood or even adulthood.

This syndrome can cause a variety of symptoms, including:

Physical Issues:

• Heart problems: These can include structural issues with the heart and blood vessels, a heart murmur (an unusual sound during a heartbeat), or bluish skin (cyanosis) due to poor blood flow.
• Frequent infections: The body's immune system might not function as well.
• Unique facial features: Some people with DiGeorge syndrome have a small chin, unusual-looking ears, wide-set eyes, hooded eyelids, and a larger-than-normal nose tip. A condition called asymmetric crying facies can also be present. This means the muscles on one side of the mouth might not develop fully, making that side droop when crying, though the face looks normal when resting.
• Cleft palate: A gap in the roof of the mouth. Other mouth or throat problems may also occur.
• Feeding difficulties: Trouble eating, not gaining enough weight, or stomach problems.
• Hearing loss: Difficulty hearing.
• Muscle weakness: Poor muscle tone.
• Kidney problems: Issues with the kidneys.
• Vision problems: Difficulties with eyesight.
• Low calcium levels: A condition that can be dangerous if left untreated.
• Scoliosis: A curvature of the spine.

Developmental and Behavioral Issues:

• Slow growth: Slower than expected growth.
• Delayed development: Delays in reaching milestones like rolling over, sitting up, or other typical infant developments.
• Speech delays: Difficulty speaking or a nasal-sounding voice.
• Learning difficulties: Problems with learning.
• Behavioral challenges: Difficulties with behavior.

Important Note: Some symptoms of DiGeorge syndrome can overlap with other conditions, particularly 22q11.2 deletion syndrome. It's crucial to see a doctor promptly if you notice any of the above symptoms in a child. Early diagnosis is important.

How Doctors Diagnose DiGeorge syndrome:

Doctors might suspect DiGeorge syndrome:

• At birth: If a child has a serious heart problem, cleft palate, or other features commonly linked to DiGeorge syndrome, doctors will likely run tests before the child leaves the hospital.
• During well-baby checkups: As the child grows, doctors may spot signs of the syndrome during regular checkups or when addressing concerns related to illness or development.

Early diagnosis and treatment can greatly improve a child's outcome. If you have any worries about your child's development or health, it's always best to talk to their doctor.

Everyone gets two copies of chromosome 22, one from each parent. People with DiGeorge syndrome have a problem with one of those copies. A small piece of chromosome 22, a region called 22q11.2, is missing. This missing piece contains about 30 to 40 genes. Scientists haven't fully figured out what many of these genes do.

This missing piece usually happens randomly. It might happen when the father's sperm is made, or in the mother's egg. Sometimes, it happens very early in the development of a baby. It's also possible, though less common, for a parent who has a similar deletion on their chromosome 22 to pass it on to their child. If a parent has the deletion, they might have fewer or less noticeable symptoms of DiGeorge syndrome.

Babies born with a missing piece of chromosome 22, in a specific area called 22q11.2, are more likely to have DiGeorge syndrome. This missing genetic material can disrupt the normal development of various parts of the body.

Birth Defects and 22q11.2 Deletion Syndrome

Several birth defects can affect a baby's health, and some of these are connected to genetic conditions like 22q11.2 deletion syndrome. This syndrome happens when a small part of chromosome 22 is missing. This missing piece can cause problems in different parts of the body.

Heart Problems:

Babies with 22q11.2 deletion syndrome often have heart defects. These problems affect how blood flows through the heart. A few examples include:

• Ventricular Septal Defect (VSD): This is a hole in the wall between the heart's lower chambers (ventricles). This allows oxygen-rich blood to flow back to the lungs instead of going to the rest of the body.
• Truncus Arteriosus: Instead of two separate blood vessels leaving the heart, there's only one large vessel. This mixes oxygen-rich blood (red) with oxygen-poor blood (blue), creating a purple mixture with insufficient oxygen for the body.
• Tetralogy of Fallot: This is a combination of four heart defects. One of these is a VSD, a hole between the heart's lower chambers. There's also a narrowing in the blood vessel leading to the lungs (pulmonary stenosis), a misplaced main artery (aorta), and a thickened wall in the lower right heart chamber (right ventricular hypertrophy). These changes affect how blood flows through the heart and to the rest of the body.

Other Issues Related to 22q11.2 Deletion Syndrome:

• Hypoparathyroidism: The parathyroid glands, located near the thyroid gland in the neck, are responsible for regulating calcium and phosphorus levels in the body. In 22q11.2 deletion syndrome, the parathyroid glands may be smaller than normal and not produce enough of the hormone that controls these minerals. This can lead to abnormally low calcium and high phosphorus in the blood.

• Thymus Gland Dysfunction: The thymus is a gland beneath the breastbone where a type of white blood cell called T cells mature. T cells are crucial for fighting infections. In 22q11.2 deletion syndrome, the thymus might be smaller or missing, which can weaken the immune system, making the person more susceptible to infections.

• Cleft Palate: A cleft palate is a split or opening in the roof of the mouth. This happens when the tissues don't completely fuse during development in the womb. Sometimes a cleft lip (split upper lip) is also present. This can cause difficulty with eating, speaking, and proper development.

• Facial Features: Some people with 22q11.2 deletion syndrome have noticeable facial features, including small, low-set ears; a small eye opening; hooded eyes; a long face; an enlarged nose tip; or a short or flattened groove in the upper lip.

• Autoimmune Conditions: People with 22q11.2 deletion syndrome may have a higher risk of developing autoimmune diseases, such as rheumatoid arthritis or Graves' disease, where the body's immune system attacks its own tissues.

• Other Problems: This syndrome can also be associated with other health issues like hearing problems, vision problems, and kidney difficulties.

It's important to note that not everyone with 22q11.2 deletion syndrome will experience all of these problems, and the severity of the symptoms can vary greatly. A healthcare professional can diagnose and manage the specific issues in each individual.

Sometimes, a parent with DiGeorge syndrome can pass it on to their child. If you have concerns about a family history of 22q11.2 deletion syndrome (which includes DiGeorge syndrome), or if you already have a child with this condition, it's a good idea to talk to a doctor who specializes in genetics. This is called a geneticist. You might also consider meeting with a genetic counselor. A genetic counselor can help you understand the risks and make plans for future pregnancies.

Doctors diagnose DiGeorge syndrome (also called 22q11.2 deletion syndrome) mainly by looking for a missing piece of chromosome 22 in a lab test. A healthcare provider might order this test if a child shows signs of the syndrome.

This syndrome can cause various health issues. If a child has a combination of problems that might be linked to 22q11.2 deletion syndrome, the doctor will likely order the chromosome test. This is especially true if the child has a heart problem, because heart conditions are frequently associated with this syndrome.

Sometimes, a child has multiple symptoms suggesting 22q11.2 deletion syndrome, but the lab test doesn't find the missing part of chromosome 22. This can happen. It's important to remember that the diagnosis isn't always straightforward. The doctor will consider all the signs and symptoms before reaching a conclusion.

DiGeorge syndrome (also called 22q11.2 deletion syndrome) is a genetic condition with no cure. However, treatments can often manage the health problems it causes. These problems can include heart defects, cleft palates, and various other medical, developmental, mental health, or behavioral issues.

Managing DiGeorge Syndrome:

The specific treatments for 22q11.2 deletion syndrome depend on the child's individual needs. Some common treatments include:

• Hypoparathyroidism: This condition affects the body's ability to produce enough parathyroid hormone, which is important for calcium regulation. Calcium and vitamin D supplements, prescribed by a doctor, are often enough to manage this. Other supplements might be needed in some cases.

• Heart Problems: Many children with 22q11.2 deletion syndrome need heart surgery soon after birth to fix any problems and improve blood flow.

• Thymus Gland Issues: The thymus gland helps the immune system develop. If a child's thymus function is somewhat weak, they might have more frequent colds or ear infections, but these are usually treated like any other child's. Most children with a moderately affected thymus will follow typical vaccination schedules, and immune function generally improves as they get older. If the thymus is severely affected or missing, the child is more vulnerable to serious infections. In these cases, treatment might involve a transplant of thymus tissue or special blood cells.

• Cleft Palate: A cleft palate (or other facial abnormalities) is often corrected with surgery.

• Developmental Needs: Children with 22q11.2 deletion syndrome may need various therapies to help them develop age-appropriate skills. This might include speech therapy, occupational therapy, and developmental therapy. Many states and counties in the U.S. offer early intervention programs to help with these therapies.

• Other Health Issues: The condition can also cause problems with feeding, growth, hearing, vision, and other medical conditions.

A Team Approach:

Because 22q11.2 deletion syndrome affects so many areas of health, a team of specialists will likely be involved in diagnosis, treatment, and care. This team might include:

• Pediatrician: A doctor specializing in children's health.
• Geneticist: A doctor who specializes in inherited conditions.
• Cardiologist: A heart specialist.
• Immunologist: A specialist in the immune system.
• ENT (Ear, Nose, and Throat) specialist: A specialist for ear, nose, and throat issues.
• Infectious disease specialist: A specialist in treating infections.
• Endocrinologist: A specialist in hormone conditions.
• Oral and Maxillofacial Surgeon: A surgeon specializing in facial and mouth issues.
• Cardiovascular Surgeon: A surgeon specializing in heart surgery.
• Occupational Therapist: Helps with daily living skills.
• Speech Therapist: Improves communication skills.
• Developmental Therapist: Helps with behavioral and social development.
• Mental Health Professional (e.g., pediatric psychiatrist or psychologist): Provides support for mental health needs.

Living with DiGeorge Syndrome:

Raising a child with 22q11.2 deletion syndrome can be challenging, as there are often multiple health concerns and treatments involved. It's helpful to reach out to organizations that provide information, support groups, and resources for parents of children with this condition. Ask your healthcare team for recommendations.