22q11.2 deletion syndrome (DiGeorge syndrome)

Overview

22q11.2 deletion syndrome occurs when one copy of a segment on the long arm of chromosome 22 is missing. The same molecular deletion was historically split into several syndromes—DiGeorge syndrome, velocardiofacial syndrome and others—because different specialties saw different parts of the phenotype. Genetic testing demonstrated that these labels often represent one variable condition. ^{[1] [2]}

Clinical expression ranges from subtle learning or palatal problems to complex congenital heart disease, severe immune deficiency or neonatal hypocalcemia. No single physical feature is present in every affected person. This variability is why diagnosis may occur in infancy, childhood or adulthood and why a checklist across multiple organ systems is more useful than looking for one “classic” appearance. ^{[1] [2]}

Symptoms and warning signs

Possible features include conotruncal congenital heart defects, cleft or submucosal cleft palate, velopharyngeal insufficiency and nasal speech, recurrent infections, low calcium with muscle cramps or seizures, feeding problems, kidney anomalies, hearing loss, short stature and developmental or learning differences. Adolescents and adults have increased rates of anxiety, ADHD, autism-spectrum features and psychotic disorders. ^{[1] [2]}

Diagnosis

Chromosomal microarray is a common first-line test because it detects the typical deletion and other copy-number changes. Targeted methods such as FISH, MLPA or quantitative PCR can confirm a known familial deletion, but older targeted FISH probes can miss atypical deletions outside the probe region. ^{[1] [2]}

After molecular diagnosis, baseline evaluation usually spans cardiology, calcium/parathyroid function, immune status, palate/feeding and speech, hearing, kidneys, growth and development. The exact tests depend on age and presentation. Genetic counseling clarifies recurrence risk and may prompt testing of parents because about 10% of cases are inherited while most arise de novo. ^{[1] [2]}

Major organ-system manifestations

Cardiac: tetralogy of Fallot, interrupted aortic arch, truncus arteriosus and other conotruncal defects are enriched. Immune: thymic hypoplasia causes variable T-cell deficiency, from mild immune differences to rare severe immunodeficiency. Endocrine: hypoparathyroidism can cause hypocalcemia, sometimes emerging during physiologic stress even when neonatal calcium was normal. Palate: overt or submucosal cleft and velopharyngeal dysfunction can impair feeding and speech. ^{[1] [2]}

Development, learning and mental health

Speech-language delay and learning difficulties are common and benefit from early educational and therapy support. Attention-deficit/hyperactivity disorder and autism-spectrum features occur more often than in the general population. Adolescents and adults have increased vulnerability to anxiety, depression and psychotic disorders, so mental-health screening should be proactive rather than waiting for crisis. ^{[1] [2]}

Treatment and management

There is no single treatment that replaces the missing chromosome segment. Care targets each manifestation: congenital heart disease may require surgery or catheter intervention; hypocalcemia is treated with calcium/vitamin D strategies; immune deficiency determines infection precautions, vaccination decisions and occasionally advanced immune therapy; palate and speech problems may require surgery and speech therapy. ^{[2] [3]}

Developmental, educational, hearing, feeding and mental-health services are integrated over time. Before live vaccines or blood products in patients with significant immune concerns, immune status should be clarified with the treating team. Because needs change with age, transition from pediatric to adult specialty care should be planned rather than assuming the syndrome is only a childhood condition. ^{[2] [3]}

Inheritance, family testing and pregnancy

22q11.2 deletion syndrome follows an autosomal-dominant inheritance pattern. Most affected people have a new (de novo) deletion, but MedlinePlus Genetics notes that about 10% inherit it from a parent. An affected person has a 50% chance of passing the deletion to each child, although the child’s severity cannot be predicted from the parent’s phenotype. ^{[1] [2]}

Adult care and transition

Adults continue to need follow-up for cardiac disease, calcium and thyroid problems, hearing, kidney issues and mental health, even if childhood surgery was successful. Pregnancy in an affected adult can add cardiac and calcium demands and also raises genetic-counseling questions. A portable summary of the molecular diagnosis and major organ history can improve care when moving between specialties. ^{[2] [3]}

Sources

1. MedlinePlus Genetics — 22q11.2 deletion syndrome
2. GeneReviews / NCBI Bookshelf — 22q11.2 Deletion Syndrome
3. NORD — 22q11.2 Deletion Syndrome
4. MedlinePlus Genetics — Chromosome 22

This article is based on trusted medical sources and is awaiting clinician review. It is not a substitute for personalized medical advice.