DiGeorge Syndrome

Why it happens

The 22q11.2 region contains about 30 to 40 genes. One important gene, TBX1, guides the development of structures from the "pharyngeal arches" in the early embryo, including the heart's outflow tract, thymus, parathyroid glands, palate and face. Missing one copy disrupts their formation, which explains why so many systems can be affected.

About 90% of deletions are new (de novo). A parent with the deletion has a 50% chance of passing it to each child. DiGeorge syndrome, velocardiofacial syndrome and conotruncal anomaly face syndrome were once thought to be separate but are now known to share this deletion. See 22q11.2 deletion syndrome.

Symptoms and features

Diagnosis

• Prenatal: suspected when an ultrasound shows certain heart defects; confirmed by testing amniotic fluid or with cell-free DNA screening followed by diagnostic testing.
• After birth: chromosomal microarray or FISH test confirms the deletion.
• Baseline checks after diagnosis: echocardiogram, calcium and parathyroid hormone levels, immune tests (T cell counts), kidney ultrasound, hearing and eye checks, and developmental assessments.
• Family testing: parents are offered testing to find out if the deletion is inherited.

Treatment

There is no cure, but each feature is treatable:

• Heart: surgery for many defects, often in infancy.
• Low calcium: calcium and active vitamin D supplements, with monitoring during illness, surgery and puberty.
• Immune system: most children need only routine monitoring and may receive live vaccines after immune testing. Children with severe T cell deficiency need specialist care, avoiding live vaccines, preventive antibiotics, and thymus tissue transplantation or bone marrow transplant.
• Palate and speech: speech therapy, palate surgery when needed.
• Feeding: feeding therapy, special bottles, treatment of reflux and constipation, sometimes a feeding tube.
• Development and education: early intervention, individualized education plans, occupational and physical therapy.
• Mental health: regular screening and early treatment of anxiety, ADHD and psychosis.

A coordinated team, often based at a specialized 22q center, helps manage the many needs over a lifetime.

Outlook

Life expectancy depends mainly on the severity of the heart defect and immune deficiency. Many people with 22q11.2 deletion live into adulthood and have jobs and families. Most adults have some ongoing health and learning needs, and lifelong medical follow-up is recommended.

Frequently asked questions

What are the symptoms of DiGeorge syndrome?

Common symptoms include heart defects, low calcium causing seizures or muscle spasms, frequent infections from a weak immune system, cleft or poorly functioning palate, feeding problems, speech delay and learning differences. Features vary widely from person to person.

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

Yes. DiGeorge syndrome, velocardiofacial syndrome and 22q11.2 deletion syndrome describe the same genetic condition. The name 22q11.2 deletion syndrome is now preferred because it describes the cause.

What is the life expectancy for DiGeorge syndrome?

Most people with DiGeorge syndrome who survive infancy live well into adulthood. Life expectancy is somewhat shorter than average, mainly because of heart disease and other medical complications. Children with severe immune deficiency need specialized treatment to survive.

Is DiGeorge syndrome inherited?

Usually not. About 90% of cases are caused by a new deletion in the child. In about 10%, the deletion is inherited from a parent, who may have mild features. An affected person has a 50% chance of passing it on to each child.