22q11.2 Deletion Syndrome (DiGeorge Syndrome)

What causes 22q11.2 deletion syndrome

Chromosome 22 has a region, called q11.2, where a stretch of about 30 to 40 genes can be lost during the formation of an egg or sperm. Losing one copy of these genes, particularly TBX1, disrupts development of structures formed early in pregnancy from the pharyngeal arches: the heart's outflow vessels, the palate, the face, the thymus (immune gland) and the parathyroid glands (calcium control).

About 90% of deletions occur for the first time in the child (de novo). The remaining 10% are inherited from a parent who has the deletion, sometimes without knowing because their symptoms are mild. An affected parent has a 50% chance of passing it on in each pregnancy.

Symptoms and features

No two people are affected the same way. Features include:

Subtle facial features may include hooded eyelids, small ears, a prominent nose with a bulbous tip, and a small mouth, but these are often hard to notice.

Diagnosis

The condition may be suspected:

• before birth, when an ultrasound shows a heart defect or cleft, with confirmation by testing amniotic fluid or placental tissue
• in a newborn with a heart defect, low calcium or immune problems
• later in childhood because of speech problems, learning difficulties or nasal speech
• in adults after a child is diagnosed, or because of psychiatric illness

Testing uses a chromosomal microarray, which detects the deletion and its size, or FISH testing for the region. Parents are usually offered testing.

After diagnosis, recommended baseline checks include an echocardiogram, calcium and parathyroid hormone levels, a full blood count, immune tests (T-cell counts), kidney ultrasound, hearing and eye exams, palate and speech assessment, and developmental evaluation.

Treatment

There is no treatment for the deletion itself. Care is managed by a team, often at a 22q specialist center:

• Heart defects: surgery, often in the first months of life.
• Low calcium: calcium and active vitamin D supplements, with monitoring during illness, surgery, pregnancy and puberty, when levels can drop.
• Immune deficiency: most children need only monitoring. Live vaccines may be delayed until immune tests are checked. Rare severe cases need thymus transplantation or specialist care.
• Palate problems: speech therapy and surgery to improve palate closure.
• Feeding: specialized bottles, feeding therapy and sometimes tube feeding.
• Development and learning: early intervention, speech and occupational therapy, and an individualized education plan.
• Mental health: regular screening for anxiety, ADHD, mood changes and early signs of psychosis, with prompt treatment.
• Other: hearing aids, treatment for thyroid or autoimmune problems, and scoliosis monitoring.

Outlook

Life expectancy depends mainly on the severity of the heart defect and immune problems. Most children who survive infancy live into adulthood, and many adults work, live independently and have families. Ongoing care into adulthood is important because new issues, such as low calcium, thyroid disease and psychiatric conditions, can appear later. Genetic counseling helps families understand recurrence risks.

Frequently asked questions

Is 22q11.2 deletion syndrome the same as DiGeorge syndrome?

Yes. DiGeorge syndrome and velocardiofacial syndrome were described separately but are now known to be caused by the same 22q11.2 deletion in most cases. "22q11.2 deletion syndrome" is the preferred umbrella term.

What is the life expectancy with 22q11.2 deletion syndrome?

Most people with the condition live into adulthood. Life expectancy is reduced on average, mainly due to serious heart defects in infancy and other complications later, but many adults live long, active lives with good medical follow-up.

Is 22q11.2 deletion syndrome inherited?

Usually not. About 90% of cases are new changes in the child. In about 10%, a parent also has the deletion. Anyone with the deletion has a 50% chance of passing it to each child.

What are the first signs of 22q11.2 deletion?

In newborns, common first signs are a heart defect, low calcium causing seizures or jitteriness, feeding difficulties, and frequent infections. In older children, nasal speech, speech delay and learning problems often lead to diagnosis.

Can 22q11.2 deletion syndrome cause mental illness?

Yes. Anxiety, ADHD and autism are common in childhood, and about 1 in 4 people develop schizophrenia or another psychotic disorder, usually in late teens or adulthood. Regular mental health screening allows early treatment.