[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Embryology](https://durgical.com/en/embryology/) › [Head and neck: pharyngeal arches](https://durgical.com/en/embryology/#a-head_neck) › 22q11.2 deletion (DiGeorge): the third and fourth pouches [Embryology](https://durgical.com/en/embryology/) · [Head and neck: pharyngeal arches](https://durgical.com/en/embryology/#a-head_neck) # 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](https://durgical.com/en/anatomy/thymus/) · [Parathyroid glands](https://durgical.com/en/anatomy/parathyroid-glands/) · [Aortic arch](https://durgical.com/en/anatomy/aortic-arch/) · [Pulmonary trunk](https://durgical.com/en/anatomy/pulmonary-trunk/) · [Soft palate](https://durgical.com/en/anatomy/soft-palate/) ## Key points - 22q11.2 deletion; key gene TBX1. - Pouches 3 and 4 fail: thymus and parathyroids. - Classic triad: conotruncal heart disease, hypocalcaemia and T-cell deficiency. - Interrupted aortic arch type B and truncus arteriosus are highly suggestive. - Diagnosis: chromosomal microarray (or FISH). ## 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. ## Memory aid Think 'pouches 3 and 4 came up empty': no thymus means no defence, no parathyroids means no calcium, and the same missing crest leaves the heart poorly divided. ## 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. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/embryology/22q11-2-deletion-the-third-and-fourth-pouches/) ## See it in 3D The structures of Durgical's 3D anatomy where it is found. - [Thymus](https://durgical.com/en/anatomy/thymus/) - [Parathyroid glands](https://durgical.com/en/anatomy/parathyroid-glands/) - [Aortic arch](https://durgical.com/en/anatomy/aortic-arch/) - [Pulmonary trunk](https://durgical.com/en/anatomy/pulmonary-trunk/) - [Soft palate](https://durgical.com/en/anatomy/soft-palate/) ## Related - [Pharyngeal pouches: tonsil, thymus, parathyroids and C cells](https://durgical.com/en/embryology/pharyngeal-pouches-tonsil-thymus-parathyroids-and-c-cells/) - [Neural crest cells and their derivatives](https://durgical.com/en/embryology/neural-crest-cells-and-their-derivatives/) - [Outflow tract: the spiral aorticopulmonary septum and neural crest](https://durgical.com/en/embryology/outflow-tract-the-spiral-aorticopulmonary-septum-and-neural-crest/) - [Tetralogy of Fallot](https://durgical.com/en/embryology/tetralogy-of-fallot/) - [Persistent truncus arteriosus](https://durgical.com/en/embryology/persistent-truncus-arteriosus/) - [Aortic arch arteries and their derivatives](https://durgical.com/en/embryology/aortic-arch-arteries-and-their-derivatives/) - [Palate: primary and secondary palate](https://durgical.com/en/embryology/palate-primary-and-secondary-palate/) - [Cleft lip and cleft palate](https://durgical.com/en/embryology/cleft-lip-and-cleft-palate/) - [Meiosis and nondisjunction: where trisomies come from](https://durgical.com/en/embryology/meiosis-and-nondisjunction-where-trisomies-come-from/) ## Related conditions - [DiGeorge syndrome (22q11.2 deletion syndrome)](https://durgical.com/en/conditions/digeorge-syndrome/) - [Hypoparathyroidism (incl. post-thyroidectomy hypocalcaemia)](https://durgical.com/en/conditions/hypoparathyroidism/) - [Hypocalcaemia](https://durgical.com/en/conditions/hypocalcaemia/) - [Tetralogy of Fallot](https://durgical.com/en/conditions/tetralogy-of-fallot/) - [Ventricular septal defect](https://durgical.com/en/conditions/ventricular-septal-defect/) [← All of embryology](https://durgical.com/en/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](https://www.ncbi.nlm.nih.gov/books/NBK549798/) (StatPearls Publishing (NCBI Bookshelf), 2025); [22q11.2 deletion syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/22q112-deletion-syndrome/) (National Library of Medicine (MedlinePlus), 2019); [Embryology, Pharyngeal Pouch - StatPearls - NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK557724/) (StatPearls Publishing (NCBI Bookshelf), 2023); Langman's Medical Embryology, 13th ed., ch. 17: Head and Neck (Wolters Kluwer, 2015). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/embryology/22q11-2-deletion-the-third-and-fourth-pouches/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/embryology/22q11-2-deletion-the-third-and-fourth-pouches/