- Author: Erawati V Bawle, MD, FAAP, FACMG; Chief Editor: Harumi Jyonouchi, MD more...
DiGeorge syndrome (DGS) is one of a group of phenotypically similar disorders—including velocardiofacial syndrome (VCFS, or Shprintzen syndrome) and conotruncal anomaly face (CTAF) syndrome—that share a microdeletion of the region, known as the DGS critical region, on chromosome 22 at band 22q11.2 (see the image below). These overlapping conditions are now termed as a 22q11.2 deletion syndrome (22q11.2DS) and in the rest of the article will be referred to as 22q11.2DS.
Although the prognosis for 22q11.2DS varies widely, depending largely on the nature and degree of involvement of different organs, many adults live long and productive lives.
Signs and symptoms
Patients with 22q11.2 DS usually have characteristic facies. Common features include the following (see the images below) :
Retrognathia or micrognathia
High and broad nasal bridge
Narrow palpebral fissures
Asymmetrical crying face
Low-set, malformed ears
Congenital heart defects, either a cleft palate or incompetence of the soft palate, and immune deficiencies are common. Patients may have short stature and occasional instances of growth hormone deficiency. Renal, pulmonary, gastrointestinal (GI), skeletal, and ophthalmologic abnormalities can also occur.
Children and adults with 22q11.2DS have high rates of behavioral, psychiatric, and communication disorders. In children, these include attention-deficit/hyperactivity disorder, anxiety, autism, and affective disorders. Adults have a high rate of psychotic disorders, particularly schizophrenia.
See Clinical Presentation for more detail.
Chromosomal microarray analysis (CMA) or array comparative genomic hybridization (aCGH)
Fluorescent in situ hybridization (FISH)
TBX1 gene studies
Multiplex ligation-dependent probe amplification (MLPA)
Additional laboratory tests
Complete blood cell (CBC) count
Serum calcium and parathyroid hormone (PTH) studies
Evaluation of T-cell count and function
Reverse-transcriptase polymerase chain reaction (RT PCR) assay to assess thymic T-cell out for detection of TCR excision circles (TREC)
Antibody response studies
Imaging studies used in the diagnosis of thymic and cardiovascular abnormalities in 22q11.2DS include the following:
Magnetic resonance imaging (MRI)
Computed tomography (CT) scanning
Angiography and magnetic resonance angiography (MRA)
See Workup for more detail.
Congenital heart defect
If a heart murmur and or other signs of a heart defect are present, consult a cardiologist right away, especially in the neonatal period.
Begin calcium supplementation after proper tests (simultaneous serum calcium and serum PTH levels) are performed. Vitamin D supplementation may become necessary.
Early thymus transplantation (ie, before the onset of infectious complications) may promote successful immune reconstitution for subjects with complete absence of thymus (1% of 22q11.2DS subjects). A potential alternative treatment, adoptive transfer of mature T cells (ATMTC) through bone marrow transplantation has emerged as a successful therapy for 22q11.2DS.
For subjects with thymic hypoplasia, prophylactic antibiosis and antifungals are helpful for the first year of life. Management of autoimmune complications are important for older subjects.
Cleft palate can be repaired with surgical modalities.
Glottic web can be managed with surgical reconstruction or tracheotomy.
Early intervention services
Monitor neurodevelopment and speech development, and refer the patient for educational therapies.
22q11.2DS (DiGeorge syndrome, or DGS) has a wide range of clinical features, including the following:
Congenital heart defects
Cognitive, behavioral, and psychiatric problems
Increased susceptibility to infections due to thymic aplasia or hypoplasia
Some collectively refer to these by the acronym CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, and hypocalcemia resulting from 22q11.2 deletion). This designation has not been in use recently. See the image below. (See DDx and Workup.)
22q11.2DS encompasses the following phenotypically similar disorders—including DiGeorge syndrome:
Velocardiofacial syndrome (VCFS, or Shprintzen syndrome)
Cayler cardiofacial syndrome (asymmetric crying facies)
Conotruncal anomaly face (CTAF) syndrome
Some cases of autosomal dominant Opitz G/BBB syndrome
These syndromes were described as separate entities based on their prominent features and prior to the discovery that the microdeletion of the DGS critical region, on band chromosome 22 at band 22q11.2 was the underlying cause in most of them.
DiGeorge syndrome was originally described as a developmental field defect in the third and fourth branchial pouches, often presenting in the neonatal period with hypocalcemia and severe immune deficiency. Later, conotruncal heart defects in DiGeorge syndrome were included. Velocardiofacial syndrome, on the other hand, was initially recognized as a syndrome of palatal defects, conotruncal heart defects, and characteristic facial features. (See Pathophysiology and Etiology.)
Immunologic classification of partial versus complete 22q11.2DS
Thymic hypoplasia or aplasia leading to defective T-cell function is one of the main features of 22q11.2DS. Depending on the T-cell proliferative responses to mitogens, the immunologic features of 22q11.2DS can be classified as partial or complete. Patients with partial 22q11.2DS have a below-normal proliferative response to mitogens, and the immune parameters may improve with time. Interleukin (IL)–7 may play a critical role in T-cell homeostasis in patients with partial 22q11.2DS. However, in subjects with thymic hypoplasia, despite compensatory increase of T-cell numbers, TCR repertoire is reported to be decreased than normal controls.
Patients with complete 22q11.2DS are rare and have no T-cell responses to mitogens. These patients usually have very few detectable T cells in peripheral blood (1-2%) and usually require treatment of thymic transplant or hematopoietic stem cell transplantation. (See Treatment and Medication.)
Although 22q11.2DS is categorized as a T-lymphocyte immunodeficiency, B-lymphocyte defects also occur. A review of 1023 patients with DGS revealed that 6% of patients older than 3 years had hypogammaglobulinemia and that 3% of patients with DGS were receiving immunoglobulin replacement therapy.
The result of the 22q11.2 deletion is a range of embryonic developmental disruptions involving the head, neck, brain, skeleton, and kidneys. Portions of the heart, head and neck, thymus, and parathyroids derive from the third and fourth pharyngeal pouches, and a developmental field defect results from the chromosomal microdeletion. This, in turn, leads to hypocalcemia and variable T-cell deficiency. A combined T- and B-cell deficiency in part results from lack of T-helper cell function as seen in cases of complete 22q11.2DS.
The syndrome is caused by a microdeletion of band 22q11.2. The long arm of chromosome 22 (at q11) is prone to a microdeletion because of the presence of nonallelic, flanking, low-copy repeat deoxyribonucleic acid (DNA) sequences labeled A-D. These sequences lead to meiotic nonallelic crossing over between the 2 copies of chromosome 22 during spermatogenesis or oogenesis.
The most common deletion present in 85% of individuals is 3 million base pair (Mb) in size, extends from A to D, and encompasses approximately 40 genes and 4 micro RNAs. Among them is the TBX1 gene, suspected to play a major role in many of the typical features of this syndrome. However, which other genes must be deleted remains unknown, and no genotype-phenotype correlation has been elucidated. The remaining 15% of affected individuals have atypical smaller deletions.
Among other genes mapped in the deleted region that have been implicated in the pathogenesis of 22q11.2DS include HIRA (a transcriptional corepressor of cell cycle–dependent histone gene transcription and mammalian homologue of the yeast Hir1p and Hir2p proteins) and UFD1L (homologue of a highly conserved yeast gene involved in the degradation of ubiquitinated genes).
Disease mechanism of immunodeficiency
The characteristic immunodeficiency in 22q11.2DS is a mild to moderate defect in T-cell lineage caused by thymic hypoplasia in subjects with incomplete DGS. Naïve T-cell production is usually reduced with resultant low TREC (T-cell receptor excision circles) detected by PCR. Only a small fraction of patients present with marked impairment of T-cell function associated with a complete absence of thymus/T-cells, and severe systemic infections, consistent with severe combined immunodeficiency phenotype. Improvement with age in T-cell functions and numbers may be attributed to homeostatic T-cell proliferation secondary to limited T-cell production.
Variable secondary humoral defects, including hypogammaglobulinemia and selective antibody deficiency, may be present.
Disease mechanism of autoimmune diseases
Impaired T-cell production may predispose patients with 22q11.2 deletion to autoimmune diseases. In a cohort of 195 patients with 22q11.2DS, various autoimmune diseases, including juvenile rheumatoid arthritis, idiopathic thrombocytopenic purpura, and autoimmune hemolytic anemia, were each more prevalent than in the age-matched general population. No specific pattern of autoimmune disease appears to be associated with 22q11.2 deletion.
The frequency of autoimmune disorders in patients with partial 22q11.2DS was reviewed by Tison et al in a large cohort of pediatric patients, and in that review, cytopenias and hypothyroidism were reported to be the most common autoimmune conditions. Autoimmunity was found in 10 (8.5%) of 130 patients, a frequency similar to that seen in a previous study in a different institution. Children with high or normal naive CD4 T-cell counts early in childhood had a lower risk of autoimmune disease.
Association with Graves disease has been reported sporadically.[8, 9] Other associated diseases include immune cytopenias, immune thrombocytopenic purpura, juvenile rheumatoid arthritis–like polyarthritis, autoimmune uveitis, and severe eczema.
DiGeorge syndrome and velocardiofacial syndrome (VCFS) have also been found to be significantly associated with asthma but not with allergic rhinitis.
Disease mechanisms of neuropsychiatric disorders
The 22q11.2 microdeletion is the strong known genetic risk factor for schizophrenia and has been implicated with microRNA (miRNA)-mediated dysregulation. Primary candidate genes for this condition are DiGeorge syndrome critical region gene 8 (DGCR8), which encodes a component of the microprocessor complex essential for miRNA biogenesis and miR-185. miR-185 is reported to be down-regulated in brains of schizophrenia patients and also is reported to be down-regulated in patients with 22q11.2 DiGeorge syndrome.
Mode of inheritance
The occurrence of 22q11.2DS is sporadic in more than 90% of cases, being the result of de novo (noninherited) deletions. About 10% have inherited the deletion from a parent as an autosomal dominant condition. Sibling involvement has been observed only if a chromosome 22 deletion has been found in a parent. The hereditary cases show no predilection in inheritance from the mother or father, and an affected person has a 50% chance of transmitting the condition to his or her child. Wide intrafamily and interfamily variability in clinical manifestations is seen.
Estimates of the incidence of 22q11.2DS range from 1 per 2000 to 1 per 4000 persons in the general population of the United States, as well as internationally. It is a frequent cause of cleft palate and congenital heart defects.
Although 22q11.2DS is a congenital condition, the age at diagnosis largely depends on its severity and on the types of birth defects it causes. Thus, patients with more serious cardiac defects or hypocalcemia are diagnosed in the neonatal period. Recurrent infections usually present in patients older than 3-6 months.
Some individuals without hypocalcemia who have normal immune function, mild cardiac defects, and minimal facial anomalies may remain undiagnosed until late childhood. Late diagnosis into adulthood continues to be reported, especially in persons with isolated mild symptoms. Prenatal diagnosis in fetuses with a congenital heart anomaly has been made frequently and should be offered to a pregnant woman at risk of carrying a fetus with this syndrome.
The prognosis for 22q11.2DS varies widely, depending largely on the nature and degree of involvement of different organs, and many adults live long and productive lives.
The most common cause of mortality in 22q11.2DS is a congenital heart defect and the second most common is severe immune deficiency. Mortality is higher in infancy because of the severity of these 2 conditions. Infants with thymus aplasia present with severe immunodeficiency and typically die of sepsis, which usually results from bacterial or fungal infections.
In a large European collaborative study, 558 patients with 22q11.2DS were evaluated using a questionnaire. Eight percent of the patients died, with more than half of the deaths occurring within the first month of life and the majority happening within 6 months of birth. Of the patients who survived, 62% had only mild learning problems or were developmentally normal. All but one of the deaths was attributable to congenital heart disease.
Genetic counseling is essential to educate parents regarding the recurrence risk of 22q11.2DS. In addition, the families of patients with clinically significant immunodeficiency should be educated regarding the potential complications from exposure to live-attenuated vaccines that include rotavirus vaccine, MMR vaccine, and chicken pox vaccine.
Patients' families often feel alone after the syndrome is diagnosed. Because of its rarity, most parents have neither heard of this disorder nor do they know anyone who has it to whom they can turn to for support. Support groups and other resources are of invaluable help in this regard. Many written educational materials are available through various organizations, including those listed below.
PO Box 2269
Cinnaminson, NJ 08077 USA
Telephone: 877-739-1849; email: firstname.lastname@example.org
15 Meriden Ave
Stourbridge, West Midlands; DY8 4QN United Kingdom
Telephone: 0800-389-1049; email: email@example.com
National Library of Medicine Genetics Home Reference: 22q11.2 deletion syndrome
National Center for Biotechnology Information (NCBI) Genes and Disease: DiGeorge syndrome
PO Box 874
Milltown, NJ 08850, USA
Telephone 1-866-823 7335); email: firstname.lastname@example.org
338 Spruce Street North
Timmins Ontario P4N 6N5 Canada
Telephone: 705-268-3099; email: email@example.com
Butts SC. The facial phenotype of the velo-cardio-facial syndrome. Int J Pediatr Otorhinolaryngol. 2009 Mar. 73(3):343-50. [Medline].
Nugent N, McGillivary A, Earley MJ. 22q11 chromosome abnormalities and the cleft service. J Plast Reconstr Aesthet Surg. 2010 Apr. 63(4):598-602. [Medline].
Cheng AT, Beckenham EJ. Congenital anterior glottic webs with subglottic stenosis: surgery using perichondrial keels. Int J Pediatr Otorhinolaryngol. 2009 Jul. 73(7):945-9. [Medline].
Tantibhaedhyangkul U, Davis CM, Noroski LM, Hanson IC, Shearer WT, Chinen J. Role of IL-7 in the regulation of T-cell homeostasis in partial DiGeorge syndrome. J Allergy Clin Immunol. 2009 Apr. 123(4):960-2.e2. [Medline].
Patel K, Akhter J, Kobrynski L, Benjamin Gathmann MA, Davis O, Sullivan KE. Immunoglobulin deficiencies: the B-lymphocyte side of DiGeorge Syndrome. J Pediatr. 2012 Nov. 161(5):950-3. [Medline].
Jawad AF, McDonald-Mcginn DM, Zackai E, Sullivan KE. Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). J Pediatr. 2001 Nov. 139(5):715-23. [Medline].
Tison BE, Nicholas SK, Abramson SL, Hanson IC, Paul ME, Seeborg FO, et al. Autoimmunity in a cohort of 130 pediatric patients with partial DiGeorge syndrome. J Allergy Clin Immunol. 2011 Nov. 128(5):1115-7.e1-3. [Medline].
Kawamura T, Nimura I, Hanafusa M, Fujikawa R, Okubo M, Egusa G, et al. DiGeorge syndrome with Graves' disease: A case report. Endocr J. 2000 Feb. 47(1):91-5. [Medline].
Ham Pong AJ, Cavallo A, Holman GH, Goldman AS. DiGeorge syndrome: long-term survival complicated by Graves disease. J Pediatr. 1985 Apr. 106(4):619-20. [Medline].
DePiero AD, Lourie EM, Berman BW, Robin NH, Zinn AB, Hostoffer RW. Recurrent immune cytopenias in two patients with DiGeorge/velocardiofacial syndrome. J Pediatr. 1997 Sep. 131(3):484-6. [Medline].
Lévy A, Michel G, Lemerrer M, Philip N. Idiopathic thrombocytopenic purpura in two mothers of children with DiGeorge sequence: a new component manifestation of deletion 22q11?. Am J Med Genet. 1997 Apr 14. 69(4):356-9. [Medline].
Sullivan KE, McDonald-McGinn DM, Driscoll DA, Zmijewski CM, Ellabban AS, Reed L, et al. Juvenile rheumatoid arthritis-like polyarthritis in chromosome 22q11.2 deletion syndrome (DiGeorge anomalad/velocardiofacial syndrome/conotruncal anomaly face syndrome). Arthritis Rheum. 1997 Mar. 40(3):430-6. [Medline].
Gottlieb C, Li Z, Uzel G, Nussenblatt RB, Sen HN. Uveitis in DiGeorge syndrome: a case of autoimmune ocular inflammation in a patient with deletion 22q11.2. Ophthalmic Genet. 2010 Mar. 31(1):24-9. [Medline]. [Full Text].
Archer E, Chuang TY, Hong R. Severe eczema in a patient with DiGeorge's syndrome. Cutis. 1990 Jun. 45(6):455-9. [Medline].
Staple L, Andrews T, McDonald-McGinn D, Zackai E, Sullivan KE. Allergies in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome) and patients with chronic granulomatous disease. Pediatr Allergy Immunol. 2005 May. 16(3):226-30. [Medline].
Forstner AJ, Degenhardt F, Schratt G, Nothen MM. MicroRNAs as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review. Front Mol Neurosci. 12/2013. 6:47.
de la Morena MT, Elitson JL, Dozmorov IM, Belkaya S, Hoover AR, Anguiano E, et al. Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome. Clin Immunol. 04/2013. 147:11-22.
Ryan AK, Goodship JA, Wilson DI, Philip N, Levy A, Seidel H, et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet. 1997 Oct. 34(10):798-804. [Medline]. [Full Text].
McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore). 2011 Jan. 90(1):1-18. [Medline].
Marcinkowski M, Bauer K, Stoltenburg-Didinger G, Vogel M, Versmold H. Fatal aspergillosis with brain abscesses in a neonate with DiGeorge syndrome. Pediatr Infect Dis J. 2000 Dec. 19(12):1214-6. [Medline].
Sánchez-Velasco P, Ocejo-Vinyals JG, Flores R, Gómez-Román JJ, Lozano MJ, Leyva-Cobián F. Simultaneous multiorgan presence of human herpesvirus 8 and restricted lymphotropism of Epstein-Barr virus DNA sequences in a human immunodeficiency virus-negative immunodeficient infant. J Infect Dis. 2001 Jan 15. 183(2):338-342. [Medline].
Minakawa S, Nakano H, Takeda H, Mizukami H, Yagihashi S, Satou T, et al. Chromosome 22q11.2 deletion syndrome associated with severe eczema. Clin Exp Dermatol. 2009 Apr. 34(3):410-1. [Medline].
Furniss F, Biswas AB, Gumber R, Singh N. Cognitive phenotype of velocardiofacial syndrome: a review. Res Dev Disabil. 2011 Nov-Dec. 32(6):2206-13. [Medline].
Hacihamdioglu B, Berberoglu M, Siklar Z, Dogu F, Bilir P, Savas Erdeve S, et al. Case report: two patients with partial DiGeorge syndrome presenting with attention disorder and learning difficulties. J Clin Res Pediatr Endocrinol. 2011. 3(2):95-7. [Medline]. [Full Text].
Antshel KM, Shprintzen R, Fremont W, Higgins AM, Faraone SV, Kates WR. Cognitive and psychiatric predictors to psychosis in velocardiofacial syndrome: a 3-year follow-up study. J Am Acad Child Adolesc Psychiatry. 2010 Apr. 49(4):333-44. [Medline]. [Full Text].
Sieberer M, Runte I, Wilkening A, Pabst B, Ziegenbein M, Haltenhof H. [Spectrum of neuropsychiatric features associated with velocardiofacial syndrome (Deletion 22q11.2)]. Fortschr Neurol Psychiatr. 2006 May. 74(5):263-74. [Medline].
Klaassen P, Duijff S, Swanenburg de Veye H, Vorstman J, Beemer F, Sinnema G. Behavior in preschool children with the 22q11.2 deletion syndrome. Am J Med Genet A. 2013 Jan. 161A(1):94-101. [Medline].
Choi JH, Shin YL, Kim GH, Seo EJ, Kim Y, Park IS, et al. Endocrine manifestations of chromosome 22q11.2 microdeletion syndrome. Horm Res. 2005. 63(6):294-9. [Medline].
Markert ML, Devlin BH, Chinn IK, McCarthy EA. Thymus transplantation in complete DiGeorge anomaly. Immunol Res. 2009. 44(1-3):61-70. [Medline].
McDonald-McGinn DM, Reilly A, Wallgren-Pettersson C, et al. Malignancy in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Am J Med Genet A. 2006 Apr 15. 140(8):906-9. [Medline].
Baylis AL, Watson PJ, Moller KT. Structural and functional causes of hypernasality in velocardiofacial syndrome. A pilot study. Folia Phoniatr Logop. 2009. 61(2):93-6. [Medline].
da Silva Dalben G, Richieri-Costa A, de Assis Taveira LA. Tooth abnormalities and soft tissue changes in patients with velocardiofacial syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Aug. 106(2):e46-51. [Medline].
Forbes BJ, Binenbaum G, Edmond JC, DeLarato N, McDonald-McGinn DM, Zackai EH. Ocular findings in the chromosome 22q11.2 deletion syndrome. J AAPOS. 2007 Apr. 11(2):179-82. [Medline].
Gilmour DF, Downey LM, Sheridan E, Long V, Bradbury J, Inglehearn CF, et al. Familial exudative vitreoretinopathy and DiGeorge syndrome: a new locus for familial exudative vitreoretinopathy on chromosome 22q11.2?. Ophthalmology. 2009 Aug. 116(8):1522-4. [Medline].
Binenbaum G, McDonald-McGinn DM, Zackai EH, Walker BM, Coleman K, Mach AM, et al. Sclerocornea associated with the chromosome 22q11.2 deletion syndrome. Am J Med Genet A. 2008 Apr 1. 146(7):904-9. [Medline]. [Full Text].
Kokitsu-Nakata NM, Guion-Almeida ML, Richieri-Costa A. 22q11 deletion syndrome and limb anomalies: report on two Brazilian patients. Cleft Palate Craniofac J. 2008 Sep. 45(5):561-6. [Medline].
Bittel DC, Yu S, Newkirk H, Kibiryeva N, Holt A 3rd, Butler MG, et al. Refining the 22q11.2 deletion breakpoints in DiGeorge syndrome by aCGH. Cytogenet Genome Res. 2009. 124(2):113-20. [Medline]. [Full Text].
Cho EH, Park BY, Cho JH, Kang YS. Comparing two diagnostic laboratory tests for several microdeletions causing mental retardation syndromes: multiplex ligation-dependent amplification vs fluorescent in situ hybridization. Korean J Lab Med. 2009 Feb. 29(1):71-6. [Medline].
Sørensen KM, Agergaard P, Olesen C, Andersen PS, Larsen LA, Ostergaard JR, et al. Detecting 22q11.2 deletions by use of multiplex ligation-dependent probe amplification on DNA from neonatal dried blood spot samples. J Mol Diagn. 2010 Mar. 12(2):147-51. [Medline]. [Full Text].
Naqvi N, Davidson SJ, Wong D, Cullinan P, Roughton M, Doughty VL, et al. Predicting 22q11.2 deletion syndrome: a novel method using the routine full blood count. Int J Cardiol. 2011 Jul 1. 150(1):50-3. [Medline].
Knutsen AP, Baker MW, Markert ML. Interpreting low T-cell receptor excision circles in newborns with DiGeorge anomaly: importance of assessing naive T-cell markers. J Allergy Clin Immunol. 2011 Dec. 128(6):1375-6. [Medline].
de Almeida JR, James AL, Papsin BC, Weksburg R, Clark H, Blaser S. Thyroid gland and carotid artery anomalies in 22q11.2 deletion syndromes. Laryngoscope. 2009 Aug. 119(8):1495-500. [Medline].
Driscoll DA. Prenatal diagnosis of the 22q11.2 deletion syndrome. Genet Med. 2001 Jan-Feb. 3(1):14-8. [Medline].
Shefi S, Raviv G, Rienstein S, Barkai G, Aviram-Goldring A, Levron J. Fish based preimplantation genetic diagnosis to prevent DiGeorge syndrome. J Assist Reprod Genet. 2009 Jul. 26(7):411-3. [Medline]. [Full Text].
McDonald-McGinn DM, Zackai EH. Genetic counseling for the 22q11.2 deletion. Dev Disabil Res Rev. 2008. 14(1):69-74. [Medline].
Fernández L, Lapunzina P, Arjona D, López Pajares I, García-Guereta L, Elorza D, et al. Comparative study of three diagnostic approaches (FISH, STRs and MLPA) in 30 patients with 22q11.2 deletion syndrome. Clin Genet. 2005 Oct. 68(4):373-8. [Medline].
Choolani M, Ho SS, Razvi K, Ponnusamy S, Baig S, Fisk NM, et al. FastFISH: technique for ultrarapid fluorescence in situ hybridization on uncultured amniocytes yielding results within 2 h of amniocentesis. Mol Hum Reprod. 2007 Jun. 13(6):355-9. [Medline].
Funke BH, Brown AC, Ramoni MF, Regan ME, Baglieri C, Finn CT, et al. A novel, single nucleotide polymorphism-based assay to detect 22q11 deletions. Genet Test. 2007 Spring. 11(1):91-100. [Medline].
Selim MA, Markert ML, Burchette JL, Herman CM, Turner JW. The cutaneous manifestations of atypical complete DiGeorge syndrome: a histopathologic and immunohistochemical study. J Cutan Pathol. 2008 Apr. 35(4):380-5. [Medline].
Bonilla FA, Bernstein IL, Khan DA, Ballas ZK, Chinen J, Frank MM, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005 May. 94(5 Suppl 1):S1-63. [Medline].
[Guideline] Gibson BE, Todd A, Roberts I, Pamphilon D, Rodeck C, Bolton-Maggs P, et al. Transfusion guidelines for neonates and older children. Br J Haematol. 2004 Feb. 124(4):433-53. [Medline].
Bassett AS, McDonald-McGinn DM, Devriendt K, Digilio MC, Goldenberg P, Habel A, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011 Aug. 159(2):332-9.e1. [Medline]. [Full Text].
Azzari C, Gambineri E, Resti M, Moriondo M, Betti L, Saldias LR, et al. Safety and immunogenicity of measles-mumps-rubella vaccine in children with congenital immunodeficiency (DiGeorge syndrome). Vaccine. 2005 Feb 25. 23(14):1668-71. [Medline].
Moylett EH, Wasan AN, Noroski LM, Shearer WT. Live viral vaccines in patients with partial DiGeorge syndrome: clinical experience and cellular immunity. Clin Immunol. 2004 Jul. 112(1):106-12. [Medline].
Perez EE, Bokszczanin A, McDonald-McGinn D, Zackai EH, Sullivan KE. Safety of live viral vaccines in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Pediatrics. 2003 Oct. 112(4):e325. [Medline].
Matarazzo P, Tuli G, Fiore L, Mussa A, Feyles F, Peiretti V, et al. Teriparatide (rhPTH) treatment in children with syndromic hypoparathyroidism. J Pediatr Endocrinol Metab. 2013 Aug 14. 1-7. [Medline].
Goldsobel AB, Haas A, Stiehm ER. Bone marrow transplantation in DiGeorge syndrome. J Pediatr. 1987 Jul. 111(1):40-4. [Medline].
Hong R. Thymus transplants: a look to the future. Birth Defects Orig Artic Ser. 1975. 11(1):357-60. [Medline].
Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE, et al. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007 May 15. 109(10):4539-47. [Medline]. [Full Text].
Ciupe SM, Devlin BH, Markert ML, Kepler TB. The dynamics of T-cell receptor repertoire diversity following thymus transplantation for DiGeorge anomaly. PLoS Comput Biol. 2009 Jun. 5(6):e1000396. [Medline]. [Full Text].
Markert ML, Devlin BH, Chinn IK, McCarthy EA, Li YJ. Factors affecting success of thymus transplantation for complete DiGeorge anomaly. Am J Transplant. 2008 Aug. 8(8):1729-36. [Medline]. [Full Text].
Markert ML, Boeck A, Hale LP, Kloster AL, McLaughlin TM, Batchvarova MN, et al. Transplantation of thymus tissue in complete DiGeorge syndrome. N Engl J Med. 1999 Oct 14. 341(16):1180-9. [Medline].
McGhee SA, Lloret MG, Stiehm ER. Immunologic reconstitution in 22q deletion (DiGeorge) syndrome. Immunol Res. 2009. 45(1):37-45. [Medline].
Rouillon I, Leboulanger N, Roger G, Maulet M, Marlin S, Loundon N, et al. Velopharyngoplasty for noncleft velopharyngeal insufficiency: results in relation to 22q11 microdeletion. Arch Otolaryngol Head Neck Surg. 2009 Jul. 135(7):652-6. [Medline].
Widdershoven JC, Stubenitsky BM, Breugem CC, MinkvanderMolen AB. Outcome of velopharyngoplasty in patients with velocardiofacial syndrome. Arch Otolaryngol Head Neck Surg. 2008 Nov. 134(11):1159-64. [Medline].
Driscoll DA, Spinner NB, Budarf ML, McDonald-McGinn DM, Zackai EH, Goldberg RB, et al. Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome. Am J Med Genet. 1992 Sep 15. 44(2):261-8. [Medline].
Jalbrzikowski M, Lazaro MT, Gao F, Huang A, Chow C, Geschwind DH, et al. Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder. PLoS One. 2015. 10 (7):e0132542. [Medline].
van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM. TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease: A Systematic Review. J Clin Immunol. 2015 May. 35 (4):416-30. [Medline].