DiGeorge Syndrome

Overview

DiGeorge syndrome is a genetic condition caused by a missing (deleted) small piece of chromosome 22, in a region called 22q11.2. Because the genes in this region are involved in the early development of several body systems, the condition can affect the heart, the immune system, calcium balance, facial features, the palate, and learning and development.

The severity and combination of features vary widely from person to person, even within the same family. Some individuals have serious problems recognized at birth, while others have milder features identified later in life. The condition is also known by other names, including 22q11.2 deletion syndrome and velocardiofacial syndrome, which historically described overlapping sets of features. Care is provided by a team of specialists and tailored to each person's needs.

Symptoms

Features vary greatly, and no single person has all of them. Possible signs and associated problems include:

• Congenital heart defects, which are common and may be detected at birth.
• Immune system problems, due to an underdeveloped thymus gland, leading to more frequent infections.
• Low calcium levels (hypocalcemia) from underactive parathyroid glands, which can cause muscle cramps, twitching, or seizures, especially in newborns.
• Cleft palate or other palate problems, which can affect feeding and speech, sometimes causing a nasal-sounding voice.
• Distinctive facial features in some individuals.
• Developmental and learning differences, delays in speech and development, and learning difficulties.
• Higher rates of certain mental health and behavioral conditions later in life.
• Feeding and growth difficulties in infancy.

Causes

DiGeorge syndrome is caused by the loss of a small segment of genetic material from one copy of chromosome 22 in the 22q11.2 region. Missing these genes disrupts the normal development of several structures before birth. Key points about the cause include:

• In most people, the deletion happens by chance during the formation of reproductive cells or early in development, with no family history.
• In a minority, it is inherited from a parent who also carries the deletion, sometimes with milder or unrecognized features.
• A person with the deletion has a chance of passing it on to their children, which is why genetic counseling is offered.

Risk Factors

The main risk factor for DiGeorge syndrome is genetic:

• A parent who carries the 22q11.2 deletion, which can be passed to a child.

In most cases, however, the deletion occurs spontaneously and is not related to anything the parents did before or during pregnancy. There are no known lifestyle or environmental causes. Because the deletion can be inherited, families affected by the condition are often referred for genetic counseling.

Diagnosis

DiGeorge syndrome is diagnosed by identifying the chromosome 22 deletion, often after certain features raise suspicion. The process may include:

• Recognition of suggestive features, such as a heart defect, low calcium, immune problems, or palate and developmental concerns.
• Genetic testing, which is the definitive way to confirm the 22q11.2 deletion. Specialized chromosome and DNA tests can detect the missing segment.
• Prenatal testing in some cases, if there is a known family history or findings on prenatal ultrasound.
• Additional evaluations to assess the heart, immune function, calcium levels, palate, hearing, and development once the diagnosis is suspected or confirmed.

Because features vary, the diagnosis is sometimes made in infancy and other times not until childhood or adulthood.

Treatment

There is no cure for DiGeorge syndrome, so care focuses on treating the specific problems each person has and supporting development. Because many systems can be involved, management usually requires a team of specialists. Treatment may include:

• Heart care, including surgery or other treatment for congenital heart defects.
• Calcium management, with calcium and vitamin D supplements to correct low levels.
• Immune support, including monitoring for infections, careful vaccination decisions, and, in rare severe cases, specialized treatment for immune deficiency.
• Palate and feeding care, including surgery for cleft palate and feeding or speech support.
• Developmental and educational support, such as early intervention, speech therapy, and learning assistance.
• Mental health and behavioral support as needed across the lifespan.

Regular follow-up across childhood and adulthood helps identify and address issues early.

Prevention

DiGeorge syndrome cannot be prevented because it is caused by a genetic change, which in most cases occurs by chance. However, families can take helpful steps:

• Genetic counseling for adults with the condition or families with a history, to understand the chance of passing it on and the options available.
• Prenatal testing in pregnancies at higher risk, which can allow for planning and early care.
• Early evaluation and follow-up after diagnosis to manage complications promptly.

When to See a Doctor

See a healthcare provider if a child has features that could suggest DiGeorge syndrome, such as a heart defect, frequent infections, feeding difficulties, developmental or speech delays, or palate problems, especially in combination.

Seek emergency care for signs of severely low calcium, such as muscle spasms, twitching, or seizures, particularly in a newborn, and for any breathing difficulty or signs of a serious infection. If a diagnosis has been made, follow the care team's plan and keep regular follow-up appointments, since needs can change over time and early treatment of complications improves outcomes.

Related Topics

Frequently Asked Questions

References

1. MedlinePlus, U.S. National Library of Medicine.
2. National Institute of Child Health and Human Development (NICHD).
3. Genetic and Rare Diseases Information Center (GARD).
4. Mayo Clinic. DiGeorge syndrome (22q11.2 deletion syndrome).