Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

DiGeorge Syndrome Treatment & Management

  • Author: Erawati V Bawle, MD, FAAP, FACMG; Chief Editor: Harumi Jyonouchi, MD  more...
 
Updated: May 17, 2016
 

Approach Considerations

A multidisciplinary team best cares for individuals with 22q11.2DS; however, one physician (usually the primary physician) must take the lead and provide a medical home for the patient. The primary physician also must monitor growth and development. A system-by-system approach results in the best outcome.

Management of 22q11.2DS includes the following:

  • Calcium supplementation: For hypoparathyroidism-associated hypocalcemia; vitamin D supplementation may also be needed
  • Surgery: Cardiovascular surgery, cleft palate repair, and, for congenital anterior glottic webs, tracheotomy or surgical reconstruction
  • Immunodeficiency: Therapies include thymus transplantation and adoptive transfer of mature T cells (ATMTC) for individuals with complete DiGeorge syndrome and appropriate prophylaxis measures and monitoring autoimmune complications for incomplete or partial DiGeorge syndrome.

Helpful clinical guideline summaries include those from the Joint Council of Allergy, Asthma and Immunology (Practice parameter for the diagnosis and management of primary immunodeficiency[51] ) and the British Committee for Standards in Haematology ([1] Transfusion guidelines for neonates and older children; [2] amendments and corrections to the transfusion guidelines for neonates and older children[52] ).

Contraception

For patients with chromosome 22q11.2 deletion syndrome, gynecologic evaluation and contraceptive education should be instituted at age 12-18 years and after age 18 years.

Follow-up

Consensus guidelines for follow-up finalized in 2010 at the International 22q11.2 Deletion Syndrome Meeting[53] for use by the international community are an excellent resource.

Next

Transfusion and Immunization in Immunodeficient Patients

The utmost care must be taken to avoid the use of nonirradiated blood products in patients with 22q11.2DS. In the presence of significant T-cell defects, transfusions with nonirradiated blood may prove fatal secondary to a graft versus host response initiated by donor lymphocytes contaminated in blood products. If a blood transfusion is necessary in infancy, use only cytomegalovirus-negative, irradiated blood products.

Do a complete blood count (CBC) at diagnosis and again at age 1-5 years. If absolute lymphopenia is present, consult an immunologist. Follow the immunologist's recommendations regarding follow-up for future immunologic issues and for immunizations.

Live vaccines are typically contraindicated in patients with 22q11.2DS and in household members of such patients because of the risk of shedding of live organisms. Adverse events and fatal reactions have been well documented after severely immunocompromised patients with 22q11.2DS have received live vaccines[54] ; however, a few studies have shown that live viral vaccines (LVVs) may be safe in select populations affected by the syndrome.

Azzari et al evaluated the safety and immunogenicity of measles-mumps-rubella (MMR) vaccine in children with DGS and found no severe adverse reactions in the 14 patients studied.[55] Patients and control subjects experienced the same frequency of seroconversion for measles and rubella. The mean titers of anti-measles or anti-rubella antibodies were the same in patients and controls, and no decrease in CD4 cells was detected after immunization.

In a study of 53 patients at Texas Children’s Hospital with partial 22q11.2DS, no significant adverse events were recorded in the 25 who received an LVV.[56]

Similarly, a retrospective analysis by Perez et al of 59 patients with 22q11.2DS who received LVV for varicella (32 patients) and MMR (52 patients) found that the incidence of adverse effects was comparable to that reported in the general population. All of the side effects were mild.[57]

Previous
Next

Management of Hypoparathyroidism and Hypocalcemia

Obtain a serum calcium level at diagnosis and repeat at ages 1-5, 6-11, 12-18, and over 18 years. If the patient is found to be hypocalcemic, begin calcium supplementation after proper tests (simultaneous serum calcium and serum parathyroid hormone [PTH] levels) are performed. Vitamin D supplementation may become necessary.

A study by Matarazzo et al indicated that in children with syndromic hypoparathyroidism, subcutaneous recombinant human PTH (rhPTH) therapy used in place of calcium and vitamin D supplementation can effectively treat hypocalcemia while sparing patients the side effects of calcium and vitamin D. In this 2.5-year, self-controlled trial, involving 6 pediatric patients (including 2 with DiGeorge syndrome), rhPTH therapy enabled 2 patients to end treatment with calcium and vitamin D, 3 patients to stop calcium therapy, and 2 patients to reduce vitamin D treatment. In 4 of the patients, fewer tetanic episodes occurred during rhPTH treatment than during conventional therapy.[58]

Previous
Next

Immunologic Therapy

Several therapies have been used to treat immunodeficiency associated with 22q11.2DS. Cases of immune reconstitution have been reported following transplantation of human leukocyte antigen (HLA) ̶ identical bone marrow, peripheral blood mononuclear cells, and fetal thymus. However, some of the patients treated may have had partial DGS, which can improve on its own, so results in certain cases may have been coincidental.

Thymus transplantation

Early thymus transplantation (ie, before the onset of infectious complications) may promote successful immune reconstitution. (Goldsobel et al reported disappointing results for thymus transplantation, but a significant number of patients in their study were lost to follow-up.[59] ) Because T-cell function may improve in patients with partial 22q11.2DS, thymus transplantation is indicated only for patients with complete 22q11.2 DS, phenotypically similar to SCID.[30, 60, 61, 62, 63]

In a study by Markert et al of 5 patients with complete 22q11.2DS who were treated with allogeneic, cultured, postnatal thymus tissue, 4 patients displayed immune reconstitution with T-cell proliferative responses to mitogens.[64]

In a follow-up study, Markert and colleagues reviewed 54 patients with complete 22q11.2DS who were enrolled in protocols for thymus transplantation and found that 1 year after transplantation, 25 of 25 subjects tested had developed polyclonal T-cell repertoires and proliferative responses to mitogens. Additionally, transplantation was fairly well tolerated; the most common adverse events were hypothyroidism and enteritis.[60]

At the time of the study’s publication, at which point posttransplant follow-up had been as long as 13 years, 33 of the 44 subjects who received a transplant were alive (75%). All deaths were reported to have occurred within 12 months of thymic transplantation.

Bone marrow transplantation

Adoptive transfer of mature T cells (ATMTC) through bone marrow transplantation has emerged as a successful therapy for complete 22q11.2DS, providing a potential alternative to thymic transplantation. Compared with thymic transplant, ATMTC is thought to be an easier procedure to accomplish and is available at more centers; however, there are differences in the nature of the T-cell reconstitution that results. Predictably, more naïve T cells and recent thymic emigrants are present in patients treated with thymus transplant.[65]

There are no significant differences in mortality between the 2 procedures, but the number of patients is too limited to conclude that the techniques are equally effective. Adoptive transfer will likely be pursued as a reasonable treatment for patients with 22q11.2DS who require immune reconstitution when thymus transplant is not available.[61]

Previous
Next

Growth and Development

Physical growth

Monitor growth in patients with 22q11.2DS. Feeding difficulties and failure to thrive are common in these patients, especially in those with a significant cleft palate. Occasionally, placement of a nasogastric or gastrostomy tube is necessary for feeding during the first 6-12 months of life. The tube provides adequate nutrition to prevent serious growth failure. Later, monitor the patient for growth hormone deficiency, which may manifest as significantly short stature or deceleration of rate of growth in height.

Psychomotor development

Also monitor the child’s development. If there is a developmental delay, refer the patient for physical therapy, occupational therapy, and speech therapy evaluations. The patient should also be referred to a psychologist in order to be screened for learning and behavioral problems, starting at age 4 years and then again at ages 6-11, 12-18, and over 18 years.

Previous
Next

Cleft Palate and Airway Correction

If present, cleft palate can be repaired with surgical modalities.[2] As patients with 22q11.2DS grow older, correction of hypernasal speech becomes important; this can be performed initially with speech therapy, but surgery may be required.[66, 67] Consult a reconstructive surgeon experienced in treating velopharyngeal incompetence (VPI). Avoid adenoidectomy, as it may worsen the VPI.

In order to establish a more competent airway in patients with 22q11.2DS, congenital anterior glottic webs can be managed with surgical reconstruction or tracheotomy.[3]

Previous
Next

Consultations

Coordinated, multidisciplinary follow-up care is necessary to ensure that patients with 22q11.2DS receive optimal medical care; the following consultations should be obtained initially and during follow up[53] :

  • Geneticist: For initial evaluation and genetic counseling; testing for 22q11.2 deletion for parents should be offered; periodic follow-up consultations are recommended to apprise the family of new developments, to reinforce the counseling and recurrence risk assessment, and to direct the family to resources in the community [46]
  • Pediatric cardiologist: For evaluation and management of cardiac disease
  • Pediatric cardiothoracic surgeon: For help in the evaluation and correction of cardiac and great vessel defects
  • Craniofacial specialist: For treatment of patients with cleft palate and feeding difficulties
  • Otolaryngologist: When recurrent otitis media occurs and may be needed to manage structural abnormalities in the airway
  • Audiologist: For hearing assessment
  • Immunologist: For evaluation of immune function and for other immunologic disorders
  • Infectious disease specialist: May assist in the management of recurrent infections
  • Ophthalmologist: For assessment of ocular malformations
  • Pediatric endocrinologist: For evaluation and management of hypocalcemia or for signs of growth hormone deficiency
  • Psychologist and psychiatrist: Starting at preschool age; psychiatric disorders are common in all patients with developmental delay; however, the association is stronger in patients with chromosome 22q11.2 deletion

Other specialists, such as an orthopedist or a nephrologist, may be needed based on the patient's signs and symptoms.

Previous
Next

Genetic Counseling and Screening

Approximately 8% of the patients with 22q11.2DS or velocardiofacial syndrome (VCFS) studied by Driscoll et al showed familial transmission of the 22q11.2 deletion.[68]

Because persons with 22q11.2 deletion have a 50% risk of transmitting it to each child, they should be offered genetic counseling, as well as fluorescent in situ hybridization (FISH) testing (by chorionic villus sampling) for prenatal detection as early as weeks 10-12 of gestation.

Studies have shown that 22q11 deletions occur in 20-30% of newborns with isolated conotruncal cardiac malformations. Therefore, screen all patients with conotruncal anomalies for 22q11 deletions, identify other family members at risk, and assess the risk in future pregnancies.

Previous
Next

Complications

Autoimmune complications are commonly seen in 22q11.2DS patients with lower T-cell numbers at initial presentation increasing the risk of autoimmune complications. Thus monitoring parameters for autoimmune hemolytic anemia, ITP, rheumatolid arthritis, autoimmune thyroiditis, etc. is required. 

Neuropsychiatric complications such as learning disabilities are aslo common and are expected to become more apparent with age. Late neuropsychiatric complications may include schizophrenia and other neuropsychiatric conditions and these complications are implicated with deletion of the DGCR8 gene that controls miRNA production.

Previous
 
 
Contributor Information and Disclosures
Author

Erawati V Bawle, MD, FAAP, FACMG Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Acknowledgements

David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Mark A Crowe, MD Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine

Mark A Crowe, MD is a member of the following medical societies: American Academy of Dermatology and North American Clinical Dermatologic Society

Disclosure: Nothing to disclose.

Daniel AC Frattarelli, MD, FAAP Senior Staff, Departments of Pediatrics and Emergency Medicine, Henry Ford Hospital

Daniel AC Frattarelli, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Clinical Pharmacology, and American Society for Clinical Pharmacology and Therapeutics

Disclosure: Nothing to disclose.

Sridhar Guduri, MD Consulting Staff, Allergy and Asthma Clinics of Ohio

Sridhar Guduri, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology and American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Iftikhar Hussain, MD Director of Allergy, Asthma, and Immunology Center, PC

Iftikhar Hussain, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American College of Physicians, American Thoracic Society, and Association of Clinical Research Professionals

Disclosure: Nothing to disclose.

Suguru Imaeda, MD Chief of Dermatology, Yale University Health Services; Chief of Dermatology, West Haven Veterans Affairs Medical Center; Assistant Professor, Department of Dermatology, Yale University School of Medicine

Suguru Imaeda, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Connecticut State Medical Society, Sigma Xi, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Elsevier Royalty Other

Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; Chief, Section of Allergy and Immunology, Washington Hospital Center; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, and Association of American Physicians

Disclosure: Alcon Consulting fee Consulting; Teva Consulting fee Consulting; Meda Honoraria Speaking and teaching; Ista Consulting fee Consulting; sunovian Consulting fee Consulting; dey Honoraria Review panel membership

Charles H Kirkpatrick, MD

Charles H Kirkpatrick is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Physicians, American Federation for Clinical Research, American Society for Clinical Investigation, and Clinical Immunology Society

Disclosure: Dyax Consulting fee Consulting

C Lucy Park, MD Head, Division of Allergy, Immunology, and Pulmonology, Associate Professor, Department of Pediatrics, University of Illinois at Chicago College of Medicine

C Lucy Park, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Medical Association, Chicago Medical Society, Clinical Immunology Society, and Illinois State Medical Society

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Patrick Htain Win MD, President/Director, Allergy, Asthma and Immunology Center, SC; Director, The Clinical Research Center of Southern Illinois, LLC

Patrick Htain Win is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, and Joint Council of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References
  1. Butts SC. The facial phenotype of the velo-cardio-facial syndrome. Int J Pediatr Otorhinolaryngol. 2009 Mar. 73(3):343-50. [Medline].

  2. 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].

  3. 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].

  4. 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].

  5. 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].

  6. 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].

  7. 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].

  8. 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].

  9. 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].

  10. 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].

  11. 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].

  12. 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].

  13. 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].

  14. Archer E, Chuang TY, Hong R. Severe eczema in a patient with DiGeorge's syndrome. Cutis. 1990 Jun. 45(6):455-9. [Medline].

  15. 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].

  16. 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.

  17. 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.

  18. 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].

  19. McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore). 2011 Jan. 90(1):1-18. [Medline].

  20. 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].

  21. 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].

  22. 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].

  23. 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].

  24. 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].

  25. 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].

  26. 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].

  27. 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].

  28. 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].

  29. Johnston PC, Donnelly DE, Morrison PJ, Hunter SJ. DiGeorge syndrome presenting as late onset hypocalcaemia in adulthood. Ulster Med J. 2008 Sep. 77(3):201-2. [Medline]. [Full Text].

  30. Markert ML, Devlin BH, Chinn IK, McCarthy EA. Thymus transplantation in complete DiGeorge anomaly. Immunol Res. 2009. 44(1-3):61-70. [Medline].

  31. 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].

  32. 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].

  33. 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].

  34. 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].

  35. 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].

  36. 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].

  37. 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].

  38. 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].

  39. 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].

  40. 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].

  41. 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].

  42. 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].

  43. 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].

  44. Driscoll DA. Prenatal diagnosis of the 22q11.2 deletion syndrome. Genet Med. 2001 Jan-Feb. 3(1):14-8. [Medline].

  45. 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].

  46. McDonald-McGinn DM, Zackai EH. Genetic counseling for the 22q11.2 deletion. Dev Disabil Res Rev. 2008. 14(1):69-74. [Medline].

  47. 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].

  48. 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].

  49. 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].

  50. 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].

  51. 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].

  52. [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].

  53. 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].

  54. Waters V, Peterson KS, LaRussa P. Live viral vaccines in a DiGeorge syndrome patient. Arch Dis Child. 2007 Jun. 92(6):519-20. [Medline]. [Full Text].

  55. 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].

  56. 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].

  57. 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].

  58. 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].

  59. Goldsobel AB, Haas A, Stiehm ER. Bone marrow transplantation in DiGeorge syndrome. J Pediatr. 1987 Jul. 111(1):40-4. [Medline].

  60. Hong R. Thymus transplants: a look to the future. Birth Defects Orig Artic Ser. 1975. 11(1):357-60. [Medline].

  61. 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].

  62. 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].

  63. 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].

  64. 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].

  65. McGhee SA, Lloret MG, Stiehm ER. Immunologic reconstitution in 22q deletion (DiGeorge) syndrome. Immunol Res. 2009. 45(1):37-45. [Medline].

  66. 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].

  67. 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].

  68. 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].

  69. 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].

  70. 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].

 
Previous
Next
 
Mother and children with 22q11.2 deletion syndrome.
An African American girl with 22q11.2 deletion syndrome.
The same child as in the previous image, showing an asymmetrical crying face.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.