Embryology · Head and neck: pharyngeal arches

22q11.2 deletion (DiGeorge): the third and fourth pouches !

Malformation

A small piece of chromosome 22 is missing. It affects the thymus, parathyroids, heart and palate, because they all depend on the same embryonic cells.

Updated 2026-11-01

See it in 3D: Thymus · Parathyroid glands · Aortic arch · Pulmonary trunk · Soft palate

What it is

22q11.2 deletion syndrome (which includes DiGeorge and velocardiofacial syndromes) is the commonest microdeletion in humans. Loss of TBX1 and neighbouring genes disturbs the third and fourth pharyngeal pouches and the neural crest that reaches them and the heart's outflow tract. So it combines a small or absent thymus, hypocalcaemia, conotruncal heart disease and palate and facial changes.

Embryological cause

Deletion on the long arm of chromosome 22 (22q11.2), almost always new; about 10% is inherited, autosomal dominant.
TBX1 is the key gene: its loss disturbs the endoderm of pouches 3 and 4 and its signalling with the mesenchyme.
The neural crest that supplies thymic and parathyroid mesenchyme, and the crest that septates the cardiac outflow tract, fail together.
Weeks 4–6: when the pouches form, the crest migrates and the truncus arteriosus divides.

Markers

TBX1
22q11.2
Neural crest

How it presents

Conotruncal heart disease: tetralogy of Fallot, truncus arteriosus, interrupted aortic arch (especially type B), ventricular septal defect and arch anomalies.
Neonatal hypocalcaemia from hypoparathyroidism: jitteriness, tetany or seizures.
Hypoplastic thymus: frequent infections from T-cell deficiency; the complete form, with no thymus, is severe.
Cleft palate (often submucous) and velopharyngeal insufficiency, with nasal speech.
Typical face (low, rotated ears, micrognathia, bulbous nose), learning difficulties and a higher risk of schizophrenia in adulthood.

Diagnosis

Chromosomal microarray: the first-line test; it also detects atypical deletions FISH may miss.
Low serum calcium and PTH.
Low T-cell counts (CD3, CD4, CD8); chest X-ray with an absent or small thymic shadow.
Echocardiogram for the heart defect; a conotruncal defect on prenatal ultrasound is a cue to offer genetic testing.

Test yourself

Think of the answer, then tap the question to see it.

Which pharyngeal pouches fail in 22q11.2 deletion syndrome?

The third and fourth, hence the small thymus and hypoparathyroidism.

Why may a newborn with DiGeorge syndrome have seizures?

From hypocalcaemia due to hypoparathyroidism, since the parathyroids come from pouches 3 and 4.

Which heart defects are typical, and which cells link them to the syndrome?

Conotruncal defects (Fallot, truncus arteriosus, interrupted aortic arch); cardiac neural crest, which septates the outflow tract, links them.

What is the first-line genetic test?

Chromosomal microarray, which detects the 22q11.2 deletion even when atypical.

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See it in 3D

The structures of Durgical's 3D anatomy where it is found.

← All of embryology

Educational content on embryonic development; not a guide to prenatal diagnosis or to medicines in pregnancy and no substitute for a health professional's advice. No doses are given.

Sources: DiGeorge Syndrome - StatPearls - NCBI Bookshelf (StatPearls Publishing (NCBI Bookshelf), 2025); 22q11.2 deletion syndrome: MedlinePlus Genetics (National Library of Medicine (MedlinePlus), 2019); Embryology, Pharyngeal Pouch - StatPearls - NCBI Bookshelf (StatPearls Publishing (NCBI Bookshelf), 2023); Langman's Medical Embryology, 13th ed., ch. 17: Head and Neck (Wolters Kluwer, 2015).

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Representative model, for educational purposes only.