DiGeorge Syndrome (22q11.2 Deletion Syndrome)

  1. Overview and Genetics
  2. Molecular Basis: TBX1 and Pharyngeal Pouch Development
  3. Cardiac Defects: Conotruncal Anomalies
  4. Immune Deficiency: Thymic Hypoplasia and T-Cell Dysfunction
  5. Hypocalcemia and Hypoparathyroidism
  6. Palatal Anomalies and Speech
  7. Neurodevelopmental and Psychiatric Features
  8. Diagnosis
  9. Management and Monitoring
  10. Key Research Papers
  11. Featured Videos
  12. Connections

Overview and Genetics

DiGeorge syndrome — now most precisely called 22q11.2 deletion syndrome (22q11DS) — is the most common microdeletion syndrome in humans, affecting approximately 1 in 2,000 to 4,000 live births. Over its history it accumulated a confusing collection of clinical names: DiGeorge syndrome (after the physician Angelo DiGeorge, who in 1965 described children with absent thymus, hypoparathyroidism, and cardiac defects), velocardiofacial syndrome (Shprintzen syndrome, named for the palate, heart, and face triad described in the 1970s), conotruncal anomaly face syndrome, and CATCH-22 (an acronym coined in the 1990s for Cardiac defects, Abnormal face, Thymic hypoplasia, Cleft palate, and Hypocalcemia, all linked to chromosome 22). Molecular genetic work in the late 1980s and early 1990s revealed that all of these apparently distinct syndromes are caused by the same interstitial deletion on the long arm of chromosome 22, centered on band q11.2. Today, 22q11.2 deletion syndrome is the preferred unified term, though DiGeorge syndrome and velocardiofacial syndrome remain widely used in clinical settings and literature.

The deletion is most commonly 3 megabases (Mb) in length, spanning a region flanked by low-copy repeat sequences (LCRs) that predispose to recurrent rearrangement through a mechanism called non-allelic homologous recombination (NAHR). A smaller nested deletion of approximately 1.5 Mb also occurs and typically produces a milder phenotype. Roughly 90% of cases are de novo — a new deletion arising during the formation of an egg or sperm, not inherited from either parent — but approximately 10% are inherited from a parent who also carries the deletion. Inheritance follows an autosomal dominant pattern: a carrier parent has a 50% chance of transmitting the deletion to each child. Parental phenotype in familial cases can range from subclinical (a parent discovered only when their child is diagnosed) to significantly affected, illustrating the extreme variability that characterizes this condition. Because a mildly affected or unaware parent can transmit the deletion to a severely affected child, genetic testing of both parents is recommended whenever a child is diagnosed.

22q11DS is not a rare curiosity of academic genetics — it is encountered across virtually every pediatric subspecialty. A cardiologist sees it in the operating room during neonatal heart surgery. A neonatologist encounters it in a baby with unexplained low calcium and seizures on day two of life. A speech pathologist notices it in a child with hypernasal speech and a history of recurrent ear infections. A psychiatrist diagnoses it after evaluating a young adult with new-onset psychosis. Understanding the full clinical spectrum of 22q11DS, its molecular basis, and the principles of its multidisciplinary management is essential for any clinician or family touched by this condition.

Molecular Basis: TBX1 and Pharyngeal Pouch Development

The critical gene within the 22q11.2 region whose haploinsufficiency (loss of one functional copy) drives most features of the syndrome is TBX1, a member of the T-box family of transcription factors. TBX1 is expressed during embryonic development in the pharyngeal endoderm, mesoderm, and surface ectoderm of the pharyngeal arches — precisely the tissues that give rise to the structures most affected in 22q11DS. The pharyngeal apparatus, which begins developing in the fourth week of gestation, consists of a series of arches, pouches, clefts, and membranes that generate some of the most anatomically complex structures in the body: the bones of the face and jaw, the great vessels of the heart, the thymus, the parathyroid glands, the middle ear and Eustachian tube, and the palate. TBX1 orchestrates the coordinated signals — including interactions with retinoic acid, fibroblast growth factors, and sonic hedgehog pathway components — that guide pharyngeal pouch cells toward their correct fates.

The third and fourth pharyngeal pouches are particularly dependent on TBX1 signaling. Under normal conditions, cells from the third pouch migrate to form the thymus (centrally and inferiorly) and the inferior parathyroid glands, while fourth pouch derivatives contribute the superior parathyroid glands. When TBX1 is haploinsufficient, these migrations are disrupted: the thymus may be hypoplastic (reduced in size), ectopic (located in an abnormal position), or in the most severe cases completely absent; the parathyroid glands are similarly reduced or absent, leading to hypoparathyroidism. The neural crest cells that migrate from the dorsal neural tube into the pharyngeal arches are also TBX1-dependent for their proper guidance, and it is the disruption of these cells' migration that leads to the conotruncal cardiac defects characteristic of the syndrome — the outflow tract of the heart (which generates the aorta, pulmonary artery, and their separation by the aortopulmonary septum) is shaped by neural crest-derived mesenchyme that requires TBX1 signaling in the surrounding pharyngeal tissue.

Beyond TBX1, the 22q11.2 region contains approximately 40 to 50 protein-coding genes, and several others contribute to specific aspects of the phenotype. DGCR8 encodes a component of the microprocessor complex that processes precursor microRNAs, and reduced DGCR8 dosage is believed to contribute to the neurodevelopmental and psychiatric features of 22q11DS, including the elevated risk for schizophrenia. CRKL encodes an adaptor protein involved in intracellular signaling downstream of growth factor receptors and contributes to cardiac and craniofacial development. HIRA is a chromatin remodeling factor involved in histone deposition and gene regulation. The phenotypic variability of 22q11DS — even among individuals with identical deletions — likely reflects the contributions of modifier genes outside the deleted region, environmental factors during development, and epigenetic differences, making straightforward genotype-phenotype prediction impossible in clinical practice.

Cardiac Defects: Conotruncal Anomalies

Congenital heart disease is the most common major structural anomaly in 22q11DS, occurring in approximately 75% of affected individuals. The characteristic defects are conotruncal anomalies — malformations of the cardiac outflow tract and great vessels that reflect failed neural crest migration during the third to fifth weeks of gestation. The most frequent individual defects, in approximate order of prevalence, are: ventricular septal defect (VSD, particularly of the conoventricular or outlet type), tetralogy of Fallot (pulmonary stenosis + VSD + overriding aorta + right ventricular hypertrophy), interrupted aortic arch (type B — interruption between the left subclavian and left carotid arteries, virtually pathognomonic for 22q11DS when found), truncus arteriosus (failure of the aortopulmonary septum to divide the common trunk into separate aorta and pulmonary artery), and pulmonary atresia with VSD. Right-sided aortic arch is also strongly associated with 22q11DS and may occur either as an isolated finding or in combination with one of the above defects.

The clinical importance of the cardiac lesions cannot be overstated. Tetralogy of Fallot and interrupted aortic arch both require surgical correction in the neonatal or early infant period. Interrupted aortic arch in particular is a ductal-dependent lesion — adequate circulation to the lower body depends on patency of the ductus arteriosus, which begins to close spontaneously in the first days of life. When the ductus closes in a baby with interrupted aortic arch, lower body perfusion collapses, causing profound metabolic acidosis, shock, and death if not urgently treated. Prostaglandin E1 infusion to keep the ductus open is initiated immediately upon suspicion of a ductal-dependent lesion, and surgical repair follows as soon as the child is stabilized. Fetal echocardiography is now widely performed when 22q11DS is detected prenatally or when conotruncal defects are identified on routine anatomy ultrasound, allowing planning for delivery at a center equipped for neonatal cardiac surgery.

An important vascular anomaly that does not require surgery in infancy but carries significant long-term implications is aberrant right subclavian artery, which occurs in a minority of 22q11DS patients and may cause dysphagia lusoria (difficulty swallowing from esophageal compression) in childhood or adulthood. Vascular ring anomalies associated with right aortic arch can similarly produce tracheoesophageal compression. Even patients without overt structural heart disease should be evaluated for aortic root dilation and vascular anomalies, as 22q11DS is associated with an increased prevalence of aortic abnormalities that may progress with age. Cardiology follow-up is lifelong, not only for surgical patients but for all individuals with 22q11DS.

Immune Deficiency: Thymic Hypoplasia and T-Cell Dysfunction

The thymus is the primary organ of T-cell maturation: immature T-cell precursors migrate from the bone marrow to the thymus, where they undergo an elaborate educational process (positive and negative selection) that produces the functional, self-tolerant T-cell repertoire that defends the body against infections and cancers while avoiding attacks on normal tissues. In 22q11DS, the thymus develops abnormally as a consequence of TBX1 haploinsufficiency disrupting the third pharyngeal pouch — the structure from which the thymus arises. The degree of thymic involvement ranges enormously across patients, from subtle thymic hypoplasia with a mildly reduced T-cell count to complete thymic aplasia with a severe combined immunodeficiency (SCID)-like picture.

In clinical practice, the great majority of 22q11DS patients fall at the mild-to-moderate end of the spectrum. They have a smaller-than-normal thymus, a reduced but not absent T-cell count (particularly naive T cells, which depend on the thymus for production), and recurrent sinopulmonary infections — particularly recurrent otitis media, sinusitis, pneumonia, and upper respiratory infections — that improve gradually as the thymus compensates over the first years of life. Many children with 22q11DS look immunologically indistinguishable from healthy peers by school age, though they may remain mildly lymphopenic and more susceptible to infection than average. Antibody responses are generally intact (B cells are thymus-independent), but some patients also have IgA deficiency or poor vaccine responses, warranting assessment of specific antibody titers to tetanus, diphtheria, and pneumococcal antigens after age-appropriate vaccination.

At the severe end of the spectrum, a small fraction of patients — perhaps 1-2% — have complete DiGeorge syndrome, defined as the near-total or total absence of thymic tissue, with T-cell counts similar to those seen in SCID. These patients are profoundly immunocompromised from birth and will develop life-threatening opportunistic infections (Pneumocystis jirovecii pneumonia, disseminated fungal infection, severe viral illness) without intervention. Complete DiGeorge syndrome is managed with thymic transplantation — implantation of thymic tissue from a postnatal donor (typically cultured thymus slices from a cardiac surgery donor) into the patient's thigh muscles, where it can establish a new site of T-cell education. This approach, pioneered at Duke University by Dr. M. Louise Markert, has shown remarkable success in reconstituting functional T-cell immunity in patients who would otherwise not survive infancy. Patients with complete DiGeorge syndrome must avoid all live vaccines (MMR, varicella, rotavirus, live attenuated influenza) until T-cell reconstitution is documented, and they require prophylaxis against Pneumocystis with trimethoprim-sulfamethoxazole from diagnosis.

An additional immune complexity in 22q11DS is a paradoxical tendency toward autoimmune disease despite the T-cell deficiency. Juvenile idiopathic arthritis, autoimmune thyroiditis, idiopathic thrombocytopenic purpura (ITP), and hemolytic anemia occur at elevated rates. The mechanism likely involves impaired thymic negative selection (with a smaller thymus, fewer self-reactive T cells are deleted) and dysregulated regulatory T-cell development, allowing autoreactive B and T cells to escape into the periphery. This autoimmune susceptibility should be kept in mind when evaluating patients with 22q11DS who develop unexplained arthritis, cytopenias, or thyroid dysfunction.

Hypocalcemia and Hypoparathyroidism

Hypocalcemia in 22q11DS results from hypoparathyroidism — absent or insufficient parathyroid glands, which are derived from the third and fourth pharyngeal pouches and therefore dependent on the same TBX1-orchestrated developmental program as the thymus. The parathyroid glands normally regulate serum calcium by secreting parathyroid hormone (PTH), which stimulates calcium release from bone, increases renal calcium reabsorption, and promotes activation of vitamin D (calcitriol) in the kidney, which in turn increases intestinal calcium absorption. When PTH is absent or insufficient, all three of these mechanisms fail simultaneously: serum calcium falls and phosphorus rises (hypocalcemia with hyperphosphatemia is the biochemical signature of hypoparathyroidism).

The most dangerous manifestation is neonatal hypocalcemic tetany or seizures, which can present in the first 24 to 72 hours of life. The newborn's calcium demands are high (calcium is actively transported across the placenta during fetal life, and this supply suddenly stops at birth), and if PTH is absent or inadequate, serum calcium may fall precipitously in the first days. Clinical features include jitteriness, irritability, prolonged QTc on ECG (calcium stabilizes cardiac membrane potential), muscular twitching, facial twitching (Chvostek sign), carpopedal spasm (Trousseau sign), and in severe cases generalized seizures. Any neonate found to have hypocalcemia without an obvious explanation (prematurity, maternal diabetes, hypomagnesemia) should have 22q11DS considered in the differential, especially if there is also a cardiac defect or lymphopenia.

Neonatal hypocalcemia in 22q11DS is treated with intravenous calcium gluconate in acute settings, followed by oral calcium and active vitamin D supplementation (calcitriol, the active form of vitamin D, bypasses the renal activation step that requires PTH). Long-term management involves oral calcium carbonate or calcium citrate supplements combined with calcitriol to maintain serum calcium in the low-normal range — targeting the lower end of normal rather than true normal, because over-treatment risks hypercalciuria, nephrocalcinosis, and kidney stones. PTH levels should be measured serially because some patients show partial recovery of parathyroid function over time, while others have persistently undetectable PTH and require lifelong supplementation.

An important clinical nuance is that hypoparathyroidism in 22q11DS is frequently latent or intermittent. Some patients are normocalcemic under baseline conditions but develop hypocalcemia during physiological stress — illness, surgery, prolonged fasting, or periods of rapid bone growth. This latent form often goes unrecognized for years, only surfacing when a teenager with 22q11DS presents with paresthesias, muscle cramps, or seizures during a febrile illness or sports training. Measuring serum calcium, phosphorus, PTH, and 25-hydroxyvitamin D at least annually — and before any elective surgical procedure — is standard of care across all ages. Surgeons and anesthesiologists caring for 22q11DS patients should be alerted to the potential need for perioperative calcium monitoring and supplementation.

Palatal Anomalies and Speech

Structural and functional palatal anomalies occur in approximately 70% of individuals with 22q11DS and represent one of the most clinically significant non-cardiac features of the syndrome because of their profound impact on feeding, speech, and quality of life from early infancy onward. The spectrum of palatal involvement ranges from overt cleft palate (a structural gap in the hard or soft palate visible on clinical examination) to submucous cleft palate (intact mucosa overlying a structural defect in the bony or muscular palate, detected only with palpation or nasopharyngoscopy) to velopharyngeal insufficiency (VPI) without any visible palatal cleft.

Velopharyngeal insufficiency is the most functionally important palatal abnormality in 22q11DS. The velopharynx is the junction between the soft palate (velum) and the posterior pharyngeal wall; during speech and swallowing, the velum normally elevates and contacts the posterior pharyngeal wall to close off the nasal cavity from the oral cavity. When the velum is structurally short, the pharynx is abnormally wide, or the palatal muscles (which are partly derived from neural crest cells disrupted by TBX1 haploinsufficiency) function poorly, the velopharyngeal mechanism closes incompletely, producing a characteristic abnormality called hypernasal speech. In hypernasal speech, air and sound energy that should be directed into the oral cavity escape into the nasal cavity, giving speech a distinctively resonant, nasal quality that is often the first clue that brings a child with 22q11DS to medical attention. Associated features include nasal air emission (audible nasal escape of air during pressure consonants like p, b, t, d, k, g) and compensatory articulation errors as the child learns to produce consonants in ways that avoid the leaking velopharynx (glottal stops substituted for oral stop consonants are classic).

Speech evaluation by a craniofacial/cleft palate team speech-language pathologist using perceptual rating scales and nasometry is standard for all children with 22q11DS. Nasopharyngoscopy (passage of a flexible endoscope through the nose to visualize the velopharynx during speech) or multiview videofluoroscopy (X-ray video of the soft palate moving during speech, combined with a barium bolus) is used to characterize the anatomy and movement of the velopharyngeal mechanism when surgical or prosthetic intervention is being planned. Surgical treatment of VPI includes pharyngeal flap surgery (which creates a permanent tissue bridge between the soft palate and posterior pharyngeal wall, narrowing the velopharyngeal port) and sphincter pharyngoplasty (which creates a muscular ring that narrows the velopharynx). Both procedures are effective for appropriate candidates but carry risks including obstructive sleep apnea (narrowing the pharynx can obstruct the airway during sleep, particularly dangerous in patients who already have cardiac disease and marginal oxygen reserve) — making polysomnography before and after surgery important. Speech therapy alone rarely resolves VPI in 22q11DS but is essential adjunctively and for articulation remediation regardless of surgical outcome.

Neurodevelopmental and Psychiatric Features

The neurodevelopmental and psychiatric phenotype of 22q11DS is arguably the most consequential aspect of the syndrome for long-term outcomes and yet was historically the least recognized. Intellectual functioning in 22q11DS spans a broad range, with most individuals scoring in the borderline intellectual functioning or mild intellectual disability range (IQ 70-85 most common; mean IQ approximately 70-75). Full IQ scores in the average range are less common but occur, particularly in familial cases where a mildly affected parent transmitted the deletion. Cognitive strengths typically include verbal memory, facial recognition, and some aspects of social cognition, while weaknesses cluster in visual-spatial processing, working memory, abstract reasoning, arithmetic, and reading fluency. This specific cognitive profile — verbal abilities relatively preserved, nonverbal and spatial abilities impaired — is sometimes described as a nonverbal learning disability (NLD) pattern, though not all patients fit neatly into this framework.

Speech and language delays are nearly universal, present in 70-90% of children with 22q11DS. Expressive language is typically more delayed than receptive language — children understand more than they can produce, and they often present initially for evaluation of language delay rather than any medical feature. The multiple contributors to speech difficulties in 22q11DS deserve separate recognition: VPI and structural palatal anomalies disrupt articulation at the phonological level; velopharyngeal dysfunction reduces intelligibility; sensorineural and conductive hearing loss (from recurrent otitis media) reduces auditory input and feedback; hypotonia of oral musculature slows motor speech development; and the cognitive profile impairs phonological processing. Early, intensive speech-language therapy addressing all these contributors simultaneously is critical and should begin before age 2, ideally while the palate is still being evaluated for surgical intervention.

The most striking and clinically significant neurodevelopmental feature of 22q11DS is its extraordinary association with schizophrenia spectrum disorders. Approximately 25 to 30% of individuals with 22q11DS develop schizophrenia or schizoaffective disorder by adulthood, representing a risk more than 25 to 30 times that of the general population. 22q11DS is currently the single strongest known genetic risk factor for schizophrenia, and individuals with 22q11DS account for approximately 1 to 2% of all schizophrenia cases in the general population — a remarkable figure for what is considered a rare syndrome. Psychosis typically emerges in late adolescence or early adulthood (ages 17-26), often preceded by a prodromal period of social withdrawal, declining school performance, subclinical perceptual disturbances, and cognitive slippage detectable on neuropsychological testing. Early identification of the prodrome and psychosis onset, followed by prompt initiation of antipsychotic medication, is associated with better long-term outcomes and is a primary reason why annual psychiatric monitoring from adolescence is recommended for all 22q11DS patients.

Additional neurodevelopmental comorbidities include autism spectrum disorder (ASD) criteria are met on formal testing in 15-50% of patients, depending on the assessment tool and criteria applied; attention-deficit/hyperactivity disorder (ADHD); anxiety disorders (particularly social anxiety and generalized anxiety, which are extremely common and can be debilitating); and mood disorders including depression and bipolar disorder. Seizures occur in approximately 5-10% of patients, sometimes related to hypocalcemia and sometimes idiopathic. Brain MRI abnormalities are found in a minority, including periventricular white matter changes, polymicrogyria, Chiari malformation, and enlarged cisterna magna, though most patients with these incidental findings do not have correspondingly severe neurological symptoms. The contribution of reduced DGCR8 dosage to abnormal microRNA processing in developing cortical neurons is actively investigated as a mechanism for the elevated schizophrenia risk.

Diagnosis

The diagnosis of 22q11DS is established by detecting the deletion at 22q11.2 using cytogenetic or molecular genetic testing. The testing landscape has evolved significantly over the past two decades, and the appropriate first-line test now depends on the clinical context. Chromosomal microarray (CMA) — also called array comparative genomic hybridization (aCGH) or SNP array — is the preferred diagnostic test for any child with unexplained intellectual disability, multiple congenital anomalies, or a clinical presentation suggesting 22q11DS. CMA simultaneously surveys the entire genome for copy number variants (deletions and duplications) at much higher resolution than conventional karyotyping, and it detects the 22q11.2 deletion with high sensitivity and specificity while also identifying other potentially relevant chromosomal variants in the same test run. For prenatal diagnosis, CMA on chorionic villus sampling (CVS) or amniocentesis fluid is the gold standard.

Historically, FISH (fluorescence in situ hybridization) with probes specific to the 22q11.2 region was the diagnostic standard and remains widely available and reliable for confirming a suspected 22q11.2 deletion when CMA is not immediately accessible. FISH detects the common 3 Mb deletion sensitively but would miss atypical deletions outside the FISH probe region — another advantage of CMA. MLPA (multiplex ligation-dependent probe amplification) targeting 22q11.2 is another molecular approach that quantifies copy number at multiple probes within the region and is both sensitive and relatively rapid.

Prenatal identification of 22q11DS occurs through several pathways. Cell-free fetal DNA (cfDNA) non-invasive prenatal testing (NIPT) screens for 22q11.2 deletion with moderate sensitivity (approximately 75-90%) and high specificity in high-risk populations, but false negatives occur and diagnostic confirmation with invasive testing is required before clinical decision-making. Fetal echocardiography performed for a conotruncal cardiac defect detected on routine anatomy ultrasound at 18-20 weeks is a common entry point — finding a conotruncal defect raises 22q11DS probability substantially, and CMA on amniocentesis should be offered. A right-sided aortic arch, even in isolation on fetal echo, warrants 22q11DS evaluation. In the newborn period, the combination of any of the following should prompt immediate genetic evaluation: conotruncal cardiac defect, neonatal hypocalcemia without clear cause, T-cell lymphopenia or thymic hypoplasia on chest imaging, cleft palate, or the characteristic facies (small jaw, low-set ears, small mouth, long face). Laboratory evaluation at the time of initial 22q11DS evaluation should include complete blood count with differential (lymphocyte count), serum calcium, phosphorus, and PTH, and echocardiography if not already performed.

Management and Monitoring

Management of 22q11DS requires a truly multidisciplinary team because the condition affects so many organ systems across the full lifespan. No single specialist can provide comprehensive care, and families benefit enormously from access to a coordinated 22q11DS clinic where genetics, cardiology, immunology, endocrinology, speech pathology, developmental pediatrics, and psychiatry work in a structured framework rather than requiring families to independently coordinate across a dozen separate departments. Established 22q11DS clinics exist at major academic medical centers in the United States (including centers at Children's Hospital of Philadelphia, University of California San Francisco, and Boston Children's Hospital) and internationally, and referral to such a clinic whenever feasible is strongly recommended.

At the time of initial diagnosis, a structured evaluation battery is indicated regardless of the presenting features: echocardiography, serum calcium and PTH, complete blood count with lymphocyte count and T-cell subset panel (CD3, CD4, CD8, CD19 counts), renal ultrasound (10-15% of patients have renal anomalies including absent kidney, horseshoe kidney, or vesicoureteral reflux), ophthalmology evaluation (posterior embryotoxon, tortuous retinal vessels, and strabismus are associated), audiometry (sensorineural and conductive hearing loss both occur), and palate evaluation by a craniofacial team. Thyroid function tests should be obtained, and spine radiographs are recommended to evaluate for cervical spine anomalies (platybasia, atlanto-axial instability, and cervical spine fusion occur and have implications for intubation during cardiac surgery). Developmental evaluation establishes a cognitive baseline and identifies early intervention needs.

Ongoing surveillance follows an age-stratified schedule. In infancy and early childhood, the priorities are cardiac surgical follow-up, calcium monitoring (at least every 6 months or with any illness), immunology (reassessing T-cell counts and vaccine responses), speech therapy initiation before age 2, and early intervention services for developmental delay. In middle childhood, school-based accommodations, individualized education plans, hearing reassessment (annual audiometry), continued speech therapy, and endocrine surveillance (thyroid function, growth monitoring) are priorities. In adolescence, annual psychiatric screening using validated instruments for psychosis prodrome (the Structured Interview for Psychosis-Risk Syndromes, SIPS) becomes critical; neuropsychological testing to guide academic planning; bone density measurement (hypocalcemia and vitamin D supplementation require monitoring for both under- and over-supplementation effects on bone); and if puberty is delayed or incomplete, endocrinology evaluation. In adulthood, continued cardiac surveillance, psychiatric care (with medication management for a significant fraction of patients), monitoring of calcium and parathyroid status, autoimmune screening, and management of ongoing intellectual disability and social support needs are central.

Genetic counseling is essential for all patients and families. Parents of a child with 22q11DS should be offered testing themselves — if a parent carries the deletion, the 50% recurrence risk affects family planning. Prenatal diagnosis options (CVS, amniocentesis, or preimplantation genetic testing for couples pursuing IVF) should be discussed. Adults with 22q11DS who are able to have children face the same 50% transmission risk per pregnancy. The 22q11.2 Deletion Syndrome Foundation and the VCFS Educational Foundation provide patient and family support resources, and connection to these organizations should be part of every new diagnosis encounter.

Key Research Papers

  1. McDonald-McGinn DM, Sullivan KE, Marino B, et al. 22q11.2 deletion syndrome. Nat Rev Dis Primers. 2015;1:15071. PMID 27189754
  2. Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159(2):332-339.e1. PMID 21570089
  3. Scambler PJ, Carey AH, Wyse RK, et al. Microdeletions within 22q11 associated with sporadic and familial DiGeorge syndrome. Genomics. 1991;10(1):201-206. PMID 1672466
  4. Garg V, Yamagishi C, Hu T, Kathiriya IS, Yamagishi H, Srivastava D. Tbx1, a DiGeorge syndrome candidate gene, is regulated by sonic hedgehog during pharyngeal arch development. Dev Biol. 2001;235(1):62-73. PMID 11412027
  5. Markert ML, Devlin BH, Alexieff MJ, et al. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007;109(10):4539-4547. PMID 17284531
  6. Murphy KC, Jones LA, Owen MJ. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry. 1999;56(10):940-945. PMID 10530637
  7. Karayiorgou M, Morris MA, Morrow B, et al. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proc Natl Acad Sci USA. 1995;92(17):7612-7616. PMID 7638642
  8. Sullivan KE. Chromosome 22q11.2 deletion syndrome and DiGeorge syndrome. Immunol Rev. 2019;287(1):186-201. PMID 30565249
  9. Swillen A, McDonald-McGinn D. Developmental trajectories in 22q11.2 deletion. Am J Med Genet C Semin Med Genet. 2015;169C(2):172-181. PMID 25989227
  10. Zinkstok JR, Boot E, Bassett AS, et al. Neurobiological perspective of 22q11.2 deletion syndrome. Lancet Psychiatry. 2019;6(11):951-960. PMID 31526712
  11. Digilio MC, Marino B, Capolino R, Dallapiccola B. Clinical manifestations of Deletion 22q11.2 syndrome (DiGeorge/velo-cardio-facial syndrome). Images Paediatr Cardiol. 2005;7(2):23-34. PMID 22368627
  12. Campbell IM, Sheppard SE, Crowley TB, et al. What is new with 22q? An update from the 22q and You Center at the Children's Hospital of Philadelphia. Am J Med Genet A. 2018;176(11):2058-2069. PMID 30307705

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