Neurogenetic syndromes

22q11.2 deletion syndrome (DiGeorge / velocardiofacial syndrome)

The most common chromosomal microdeletion syndrome — congenital heart disease, immune deficiency, hypocalcaemia, learning difficulties and a high lifetime risk of psychiatric illness, with screening for psychosis from adolescence.

22q11.2 deletion syndrome is the most common chromosomal microdeletion in humans, affecting about 1 in 2,000 to 1 in 4,000 live births. It is caused by a typically 3-Mb deletion on the long arm of chromosome 22 that removes around 50 genes, including TBX1 — whose role in pharyngeal-arch development underlies most of the physical findings (congenital heart disease in 60–80%, palatal anomalies, thymic hypoplasia with T-cell immunodeficiency, parathyroid hypoplasia with hypocalcaemia, distinctive facial features). Neurodevelopmentally, it carries one of the highest known monogenic / genomic risks for serious psychiatric illness: about 30% of adults with 22q11.2DS develop psychosis (often a schizophrenia-spectrum disorder) by the third decade. Intellectual disability is mild in most cases (mean IQ ~70), with specific weaknesses in mathematics and visuospatial reasoning. Modern care is multidisciplinary, lifelong, and increasingly emphasises early identification of psychiatric prodrome from adolescence onwards.

At a glance

Cause: ~3-Mb deletion on chromosome 22q11.2 (including TBX1); most are de novo, ~10% inherited
Heart: Congenital heart disease in 60–80% — tetralogy of Fallot, interrupted aortic arch, VSD, truncus arteriosus
Common features: Palatal anomalies, T-cell immunodeficiency, hypocalcaemia, learning difficulties, characteristic facies, renal anomalies
Psychiatric risk: Schizophrenia-spectrum disorder in ~30% of adults; anxiety, ADHD, autism, OCD common in childhood
Surveillance: Lifelong: cardiology, immunology, ENT, calcium, endocrine, developmental + psychiatric from adolescence

What it is

22q11.2 deletion syndrome is the unifying diagnosis behind several conditions that were originally described separately — DiGeorge syndrome (the cardiac–thymic–parathyroid picture in infancy), velocardiofacial syndrome (the speech, palatal and facial features), and conotruncal anomaly face syndrome. They are all caused by the same recurrent microdeletion on chromosome 22, made possible by the unusual segmental-duplication architecture of that region. The full syndrome is variable; not every child has heart disease, immune deficiency or psychiatric illness, but every child needs structured multisystem surveillance because any of these features can be missed in isolation.

How it presents

Presentations span the lifespan:

Newborn — heart murmur or duct-dependent congenital heart disease; hypocalcaemic seizures; infections related to T-cell deficiency; nasal regurgitation from palatal incompetence
Infant — feeding difficulties (palatal, swallowing); failure to thrive; recurrent infections; delayed motor and speech milestones
Toddler — characteristic facial features (long face, hooded eyelids, tubular nose, small mouth, prominent nasal root); hypernasal speech, language delay
School-age — specific learning difficulties (especially mathematics, visuospatial); ADHD; anxiety; social communication differences
Adolescent — emerging psychiatric symptoms (anxiety, mood disorder, prodromal psychosis); educational challenges intensify
Adult — schizophrenia-spectrum disorder in about 30%; early-onset Parkinson's disease in a small minority

Diagnosis

Diagnostic testing is by chromosomal microarray (CMA), MLPA, or targeted FISH for 22q11.2. Whole-exome and whole-genome sequencing detect the deletion if a single-nucleotide approach is used (whole-genome sequencing is best). Most children today are diagnosed by CMA performed because of congenital heart disease or developmental delay; a meaningful minority are diagnosed in adulthood for the first time after a psychiatric presentation.

Surveillance

The International 22q11.2 Deletion Syndrome Consortium guidelines (most recent comprehensive update 2023) recommend a structured lifelong surveillance schedule:

Cardiology — echocardiogram at diagnosis; lifelong follow-up if structural lesion present
Immunology — T-cell subsets in infancy; lifelong vaccination guidance (live vaccines individualised)
Calcium — measure at diagnosis, with intercurrent illness, before any surgery (anaesthetic risk), and during adolescence (high-risk period for symptomatic hypocalcaemia)
ENT — palate assessment; hearing; adenoidectomy contraindicated in many because it worsens velopharyngeal incompetence
Endocrine — growth, puberty, thyroid; calcium / parathyroid annually
Renal — ultrasound once (renal anomalies in 30%)
Developmental — neurodevelopmental assessment at school entry; tailored learning support; speech and language therapy
Mental health — anxiety and ADHD screening throughout childhood; structured psychiatric screening from age 12 (annual) using validated tools like the Structured Interview for Prodromal Syndromes; early intervention services if prodromal psychosis identified

Treatment by manifestation

No curative treatment exists. Care is symptom-driven and multidisciplinary:

Congenital heart disease — surgical / catheter-based correction in infancy where indicated, with cardiology follow-up for life
Hypocalcaemia — calcium and active vitamin D (calcitriol or alfacalcidol); regular monitoring
Immune deficiency — IVIG in severe cases; antibiotic prophylaxis; careful vaccination programme
Palatal anomalies — speech and language therapy; pharyngoplasty if needed
Learning difficulties — individualised education plan; mathematics-specific intervention
ADHD — stimulant medications safe and effective; psychiatric monitoring
Anxiety and mood disorders — CBT first-line; SSRIs with careful monitoring
Prodromal psychosis — early intervention referral; second-generation antipsychotics if psychosis emerges; clozapine in treatment-resistant cases (acceptable but careful neutrophil monitoring given baseline immune issues)

Prognosis

With modern multidisciplinary care, life expectancy is shortened only modestly compared with the unaffected population — driven primarily by the cardiac and psychiatric outcomes. Most adults are independent or semi-independent. The mental-health outcomes — particularly the 30% schizophrenia-spectrum risk — drive most of the long-term morbidity, which is why early identification and intervention from mid-adolescence is now central to 22q11.2DS care.

How an educational review can help

Families navigating 22q11.2DS often have many appointments across many specialties and find it hard to see the whole picture. An educational review can pull the cardiac, immune, endocrine, developmental and psychiatric strands together against the 2023 international guidelines, and help you prepare focused questions about the right surveillance schedule, the timing of psychiatric screening, and the educational plan.

It is an educational second opinion — not a diagnosis, treatment or prescription — and it does not replace the care of your child's own clinicians.

Selected sources

Boot E, Óskarsdóttir S et al. Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome. Genet Med. 2023; 25: 1605–1631.
Boot E et al. Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome. Genet Med. 2023; 25: 1605–1631.
Schneider M et al. Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome. Am J Psychiatry. 2014; updated 2023.
Bassett AS et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011 / 2024 update.

Last reviewed: 2026-05-27

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