vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v15i6.1656vsp-1697Research ArticleОБЗОРЫ ЛИТЕРАТУРЫLITERATURE REVIEWСиндром делеции 22q11.2: симптомы, диагностика, лечение22q11.2 Deletion Syndrome: Symptoms, Diagnosis, Treatmenthttps://orcid.org/0000-0002-2209-7531Намазова-БарановаЛ. С.Namazova-BaranovaLeyla S.

доктор медицинских наук, профессор, академик РАН, заместитель директора НЦЗД по научной работе, директор НИИ педиатрии Адрес: 119991, Ломоносовский пр-т, д. 2, стр. 1, тел.: +7 (499) 783-27-93

Moscow, Russian Federation

namazova@nczd.ruhttps://orcid.org/0000-0002-8740-2728ГинтерО. В.GinterOlga V.

Москва, Российская Федерация

Moscow, Russian Federation

ПолунинаТ. А.PoluninaTatyana A.

Москва, Российская Федерация

Moscow, Russian Federation

https://orcid.org/0000-0002-7780-6737ДавыдоваИ. В.DavydovaIrina V.

Москва, Российская Федерация

Moscow, Russian Federation

СавостьяновК. В.SavostyanovKirill V.

Москва, Российская Федерация

Moscow, Russian Federation

ПушковА. А.PushkovAlexandr A.

Москва, Российская Федерация

Moscow, Russian Federation

ЖурковаН. В.JourkovaNatalya V.

Москва, Российская Федерация

Moscow, Russian Federation

МосьпанТ. Я.MospanTatyana Y.

Москва, Российская Федерация

Moscow, Russian Federation

Научный центр здоровья детей Первый Московский государственный медицинский университет им. И.М. Сеченова Российский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияScientific Center of Children’s Health Sechenov First Moscow State Medical University Pirogov Russian National Research Medical UniversityRussian FederationНаучный центр здоровья детейРоссияScientific Center of Children’s HealthRussian FederationНаучный центр здоровья детей Первый Московский государственный медицинский университет им. И.М. СеченоваРоссияScientific Center of Children’s Health Sechenov First Moscow State Medical UniversityRussian Federation201629122016156590595Copyright © Намазова-Баранова Л.С., Гинтер О.В., Полунина Т.А., Давыдова И.В., Савостьянов К.В., Пушков А.А., Журкова Н.В., Мосьпан Т.Я., 20162016Намазова-Баранова Л.С., Гинтер О.В., Полунина Т.А., Давыдова И.В., Савостьянов К.В., Пушков А.А., Журкова Н.В., Мосьпан Т.Я.Namazova-Baranova L.S., Ginter O.V., Polunina T.A., Davydova I.V., Savostyanov K.V., Pushkov A.A., Jourkova N.V., Mospan T.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/1697

Статья посвящена анализу последствий хромосомной аномалии в результате делеции участка длинного плеча хромосомы 22. Это приводит к многообразным клиническим проявлениям: врожденным порокам сердца, аномалиям развития крупных сосудов, врожденным порокам челюстно-лицевой области, а также эндокринным и иммунным нарушениям. Синдром делеции 22q11.2 — del 22q11.2 (22q11DS) — может проявляться более чем 180 различными физическими, функциональными и психическими ассоциациями, что оказывает влияние на здоровье и качество жизни пациента уже с рождения. Постановка клинического диагноза и ранняя диагностика играют существенную роль в оптимизации лечения, а осведомленность и понимание патологических процессов при del 22q11.2 однозначно предполагают использование принципов мультидисциплинарного лечения. В данной статье описано современное научное понимание синдрома делеции 22q11.2, основанное на опыте зарубежных и отечественных авторов. Описаны основные клинические симптомы, диагностика и рекомендации по обследованию и лечению данной категории больных.

The article analyzes the consequences of chromosomal abnormalities caused by the deletion of a small piece of chromosome 22. This syndrome results in diverse clinical manifestations: congenital heart defects, abnormalities in the large vessels, congenital defects in the maxillofacial area, as well as the endocrine and immune disorders. 22q11.2 deletion syndrome — del 22q11.2 (22q11DS) may have more than 180 different physical, functional and mental associations that affect the patient’s health and quality of life since very birth. Clinical diagnosis and early diagnostics are essential to optimize treatment, and awareness and understanding of the pathological processes in del 22q11.2 definitely involve the use of the multidisciplinary treatment principles. The article describes the modern scientific understanding of 22q11.2 deletion syndrome based on the experience of foreign and Russian authors. The basic clinical symptoms, diagnosis and recommendations for screening and treatment of this kind of patients are described.

делеция 22q11.2детисиндромхромосомахромосомные болезни22q11.2 deletionchildrensyndromechromosomechromosomal diseaseReferencesBotto LD, May K, Fernhoff PM, et al. A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics. 2003;112(1 Pt 1): 101–107. doi: 10.1542/peds.112.1.101.Botto LD, May K, Fernhoff PM, et al. A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics. 2003;112(1 Pt 1): 101–107. doi: 10.1542/peds.112.1.101.Delio M, Guo T, McDonald-McGinn DM, et al. Enhanced maternal origin of the 22q11.2 deletion in velocardiofacial and DiGeorge syndromes. Am J Hum Genet. 2013;92(3):439– 447. doi: 10.1016/j.ajhg.2013.01.018.Delio M, Guo T, McDonald-McGinn DM, et al. Enhanced maternal origin of the 22q11.2 deletion in velocardiofacial and DiGeorge syndromes. Am J Hum Genet. 2013;92(3):439– 447. doi: 10.1016/j.ajhg.2013.01.018.McDonald-McGinn DM, Tonnesen MK, Laufer-Cahana A, et al. Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net. Genet Med. 2001; 3(1):23–29. doi: 10.109700125817-200101000-00006.McDonald-McGinn DM, Tonnesen MK, Laufer-Cahana A, et al. Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net. Genet Med. 2001; 3(1):23–29. doi: 10.109700125817-200101000-00006.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.e331–339.e331. doi: 10.1016/j.jpeds.2011.02.039.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.e331–339.e331. doi: 10.1016/j.jpeds.2011.02.039.Repetto GM, Guzman ML, Delgado I, et al. Case fatality rate and associated factors in patients with 22q11 microdeletion syndrome: a retrospective cohort study. BMJ Open. 2014;4(11):e0050415. doi: 10.1136/bmjopen-2014-005041.Repetto GM, Guzman ML, Delgado I, et al. Case fatality rate and associated factors in patients with 22q11 microdeletion syndrome: a retrospective cohort study. BMJ Open. 2014;4(11):e0050415. doi: 10.1136/bmjopen-2014-005041.McDonald-McGinn DM, Minugh-Purvis N, Kirschner RE, et al. The 22q11.2 deletion in African-American patients: an underdiagnosed population? Am J Med Genet A. 2005;134(3):242–246. doi: 10.1002/ajmg.a.30069.McDonald-McGinn DM, Minugh-Purvis N, Kirschner RE, et al. The 22q11.2 deletion in African-American patients: an underdiagnosed population? Am J Med Genet A. 2005;134(3):242–246. doi: 10.1002/ajmg.a.30069.Tenas Du Montcel S, Mendizabai H, Ayme S, et al. Prevalence of 22q11 microdeletion. J Med Genet. 1996;33(8):719. doi: 10.1136/jmg.33.8.719.Tenas Du Montcel S, Mendizabai H, Ayme S, et al. Prevalence of 22q11 microdeletion. J Med Genet. 1996;33(8):719. doi: 10.1136/jmg.33.8.719.sign.ac.uk [Internet]. Scottish Intercollegiate Guidelines Network. World Wide Web 2011 [cited 2016 Oct 19]. Available from: http://www.sign.ac.uk/.sign.ac.uk [Internet]. Scottish Intercollegiate Guidelines Network. World Wide Web 2011 [cited 2016 Oct 19]. Available from: http://www.sign.ac.uk/.Harbour R, Miller J. A new system for grading recommendations in evidence based guidelines. BMJ. 2001;323(7308):334–336. doi: 10.1136/bmj.323.7308.334.Harbour R, Miller J. A new system for grading recommendations in evidence based guidelines. BMJ. 2001;323(7308):334–336. doi: 10.1136/bmj.323.7308.334.DiGeorge AM. Congenital absence of the thymus and its immunologic consequences: concurrence with congenital hypoparathyroidism. In: Bergma D, Good RA, editors. Immunologic deficiency diseases in man. New York: The National Foundation; 1968. p. 116– 121.DiGeorge AM. Congenital absence of the thymus and its immunologic consequences: concurrence with congenital hypoparathyroidism. In: Bergma D, Good RA, editors. Immunologic deficiency diseases in man. New York: The National Foundation; 1968. p. 116– 121.Scambler PJ, Carey AH, Wyse RK, et al. Microdeletions within 22q11 associated with sporadic and familial DiGeorge syndrome. Genomics. 1991;10(1):201–206. doi: 10.1016/0888-7543(91)90501-5.Scambler PJ, Carey AH, Wyse RK, et al. Microdeletions within 22q11 associated with sporadic and familial DiGeorge syndrome. Genomics. 1991;10(1):201–206. doi: 10.1016/0888-7543(91)90501-5.Demczuk S, Desmaze C, Aikem M, et al. Molecular cytogenetic analysis of a series of 23 DiGeorge syndrome patients by fluorescence in situ hybridization. Ann Genet. 1994;37(2):60-65.Demczuk S, Desmaze C, Aikem M, et al. Molecular cytogenetic analysis of a series of 23 DiGeorge syndrome patients by fluorescence in situ hybridization. Ann Genet. 1994;37(2):60-65.Gong W, Emanuel BS, Collins J, et al. A transcription map of the DiGeorge and velo- cardio-facial syndrome minimal critical region on 22q11. Hum Mol Genet. 1996;5(6):789– 800. doi: 10.1093/hmg/5.6.789.Gong W, Emanuel BS, Collins J, et al. A transcription map of the DiGeorge and velo- cardio-facial syndrome minimal critical region on 22q11. Hum Mol Genet. 1996;5(6):789– 800. doi: 10.1093/hmg/5.6.789.Kinouchi A, Mori K, Ando M, Takao A. Facial appearance of patients with conotruncal anomalies. Pediatr Jpn. 1976; 17(1):84–87.Kinouchi A, Mori K, Ando M, Takao A. Facial appearance of patients with conotruncal anomalies. Pediatr Jpn. 1976; 17(1):84–87.Shprintzen RJ. The name game. Perspectives of the ASHA Special Interest Groups. 1998;8:7–11. doi: 10.1044/ssod8.1.7.Shprintzen RJ. The name game. Perspectives of the ASHA Special Interest Groups. 1998;8:7–11. doi: 10.1044/ssod8.1.7.Bailey JA, Yavor AM, Viggiano L, et al. Human-specific duplication and mosaic transcripts: the recent paralogous structure of chromosome 22. Am J Hum Genet. 2002;70(1):83–100. doi: 10.1086/338458.Bailey JA, Yavor AM, Viggiano L, et al. Human-specific duplication and mosaic transcripts: the recent paralogous structure of chromosome 22. Am J Hum Genet. 2002;70(1):83–100. doi: 10.1086/338458.Babcock M, Pavlicek A, Spiteri E, et al. Shuffling of genes within low-copy repeats on 22q11 (LCR22) by Alu-mediated recombination events during evolution. Genome Res. 2003;13(12):2519–2532. doi: 10.1101/gr.1549503.Babcock M, Pavlicek A, Spiteri E, et al. Shuffling of genes within low-copy repeats on 22q11 (LCR22) by Alu-mediated recombination events during evolution. Genome Res. 2003;13(12):2519–2532. doi: 10.1101/gr.1549503.Yagi H, Furutani Y, Hamada H, et al. Role of TBX1 in human del22q11.2 syndrome. Lancet. 2003;362(9393):1366–1373. doi: 10.1016/S0140-6736(03)14632-6.Yagi H, Furutani Y, Hamada H, et al. Role of TBX1 in human del22q11.2 syndrome. Lancet. 2003;362(9393):1366–1373. doi: 10.1016/S0140-6736(03)14632-6.Guna A, Butcher NJ, Bassett AS. Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms. J Neurodev Disord. 2015;7(1):18. doi: 10.1186/s11689-015-9113-x.Guna A, Butcher NJ, Bassett AS. Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms. J Neurodev Disord. 2015;7(1):18. doi: 10.1186/s11689-015-9113-x.Zhang Z, Huynh T, Baldini A. Mesodermal expression of Tbx1 is necessary and sufficient for pharyngeal arch and cardiac outflow tract development. Development. 2006;133(18):3587–3595. doi: 10.1242/dev.02539.Zhang Z, Huynh T, Baldini A. Mesodermal expression of Tbx1 is necessary and sufficient for pharyngeal arch and cardiac outflow tract development. Development. 2006;133(18):3587–3595. doi: 10.1242/dev.02539.Papangeli I, Scambler P. The 22q11 deletion: DiGeorge and velocardiofacial syndromes and the role of TBX1. Wiley Interdiscip Rev Dev Biol. 2013;2(3):393–403. doi: 10.1002/wdev.75.Papangeli I, Scambler P. The 22q11 deletion: DiGeorge and velocardiofacial syndromes and the role of TBX1. Wiley Interdiscip Rev Dev Biol. 2013;2(3):393–403. doi: 10.1002/wdev.75.Calmont A, Ivins S, Van Bueren KL, et al. Tbx1 controls cardiac neural crest cell migration during arch artery development by regulating Gbx2 expression in the pharyngeal ectoderm. Development. 2009;136(18):3173–3183. doi: 10.1242/dev.028902.Calmont A, Ivins S, Van Bueren KL, et al. Tbx1 controls cardiac neural crest cell migration during arch artery development by regulating Gbx2 expression in the pharyngeal ectoderm. Development. 2009;136(18):3173–3183. doi: 10.1242/dev.028902.Cioffi S, Martucciello S, Fulcoli FG, et al. Tbx1 regulates brain vascularization. Hum Mol Genet. 2014;23(1):78–89. doi: 10.1093/hmg/ddt400.Cioffi S, Martucciello S, Fulcoli FG, et al. Tbx1 regulates brain vascularization. Hum Mol Genet. 2014;23(1):78–89. doi: 10.1093/hmg/ddt400.Sellier C, Hwang VJ, Dandekar R, et al. Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome. PLoS ONE. 2014;9(8):e103884. doi: 10.1371/journal.pone.0103884.Sellier C, Hwang VJ, Dandekar R, et al. Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome. PLoS ONE. 2014;9(8):e103884. doi: 10.1371/journal.pone.0103884.Guris DL, Fantes J, Tara D, et al. Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome. Nat Genet. 2001;27(3):293– 298. doi: 10.1038/85855.Guris DL, Fantes J, Tara D, et al. Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome. Nat Genet. 2001;27(3):293– 298. doi: 10.1038/85855.Racedo SE, McDonald-McGinn DM, Chung JH, et al. Mouse and human CRKL is dosage sensitive for cardiac outflow tract formation. Am J Hum Genet. 2015;96(2):235–244. doi: 10.1016/j.ajhg.2014.12.025.Racedo SE, McDonald-McGinn DM, Chung JH, et al. Mouse and human CRKL is dosage sensitive for cardiac outflow tract formation. Am J Hum Genet. 2015;96(2):235–244. doi: 10.1016/j.ajhg.2014.12.025.Bedeschi MF, Colombo L, Mari F, et al. Unmasking of a recessive SCARF2 mutation by a 22q11.12 de novo deletion in a patient with Van den Ende–Gupta syndrome. Mol Syndromol. 2010;1(5): 239–245. doi: 10.1159/000328135.Bedeschi MF, Colombo L, Mari F, et al. Unmasking of a recessive SCARF2 mutation by a 22q11.12 de novo deletion in a patient with Van den Ende–Gupta syndrome. Mol Syndromol. 2010;1(5): 239–245. doi: 10.1159/000328135.Bassett AS, Caluseriu O, Weksberg R, et al. Catechol-O-methyl transferase and expression of schizophrenia in 73 adults with 22q11 deletion syndrome. Biol Psychiatry. 2007;61(10):1135–1140. doi: 10.1016/j.biopsych.2006.07.038.Bassett AS, Caluseriu O, Weksberg R, et al. Catechol-O-methyl transferase and expression of schizophrenia in 73 adults with 22q11 deletion syndrome. Biol Psychiatry. 2007;61(10):1135–1140. doi: 10.1016/j.biopsych.2006.07.038.Peyvandi S, Lupo PJ, Garbarini J, et al. 22q11.2 deletions in patients with conotruncal defects: data from 1,610 consecutive cases. Pediatr Cardiol. 2013;34(7):1687–1694. doi: 10.1007/s00246-013-0694-4.Peyvandi S, Lupo PJ, Garbarini J, et al. 22q11.2 deletions in patients with conotruncal defects: data from 1,610 consecutive cases. Pediatr Cardiol. 2013;34(7):1687–1694. doi: 10.1007/s00246-013-0694-4.Keyte AL, Alonzo-Johnsen M, Hutson MR. Evolutionary and developmental origins of the cardiac neural crest: building a divided outflow tract. Birth Defects Res C Embryo Today. 2014;102(3): 309–323. doi: 10.1002/bdrc.21076.Keyte AL, Alonzo-Johnsen M, Hutson MR. Evolutionary and developmental origins of the cardiac neural crest: building a divided outflow tract. Birth Defects Res C Embryo Today. 2014;102(3): 309–323. doi: 10.1002/bdrc.21076.McElhinney DB, McDonald-McGinn D, Zackai EH, Goldmuntz E. Cardiovascular anomalies in patients diagnosed with a chromosome 22q11 deletion beyond 6 months of age. Pediatrics. 2001;108(6): E104. doi: 10.1542/peds.108.6.e104.McElhinney DB, McDonald-McGinn D, Zackai EH, Goldmuntz E. Cardiovascular anomalies in patients diagnosed with a chromosome 22q11 deletion beyond 6 months of age. Pediatrics. 2001;108(6): E104. doi: 10.1542/peds.108.6.e104.John AS, McDonald-McGinn DM, Zackai EH, Goldmuntz E. Aortic root dilation in patients with 22q11.2 deletion syndrome. Am J Med Genet A. 2009;149A(5):939–942. doi: 10.1002/ajmg.a.32770.John AS, McDonald-McGinn DM, Zackai EH, Goldmuntz E. Aortic root dilation in patients with 22q11.2 deletion syndrome. Am J Med Genet A. 2009;149A(5):939–942. doi: 10.1002/ajmg.a.32770.McElhinney DB, Clark BJ, III, Weinberg PM, et al. Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and branching. J Am Coll Cardiol. 2001;37(8):2114–2119. doi: 10.1016/S0735-1097(01)01286-4.McElhinney DB, Clark BJ, III, Weinberg PM, et al. Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and branching. J Am Coll Cardiol. 2001;37(8):2114–2119. doi: 10.1016/S0735-1097(01)01286-4.Федеральные клинические рекомендации по диагностике и лечению синдрома делеции 22-й хромосомы. — М.: ФНКЦ ДГОИ им. Д. Рогачева; 2014. — 12 с. [Federal’nye klinicheskie rekomendatsii po diagnostike i lecheniyu sindroma deletsii 22-i khromosomy. Moscow: FNKTs DGOI im. D. Rogacheva; 2014. 12 p. (In Russ).]Федеральные клинические рекомендации по диагностике и лечению синдрома делеции 22-й хромосомы. — М.: ФНКЦ ДГОИ им. Д. Рогачева; 2014. — 12 с. [Federal’nye klinicheskie rekomendatsii po diagnostike i lecheniyu sindroma deletsii 22-i khromosomy. Moscow: FNKTs DGOI im. D. Rogacheva; 2014. 12 p. (In Russ).]Козлова Ю.О. Разработка технологии пре- и постнатальной диагностики группы синдромов, обусловленных микроделецией 22q11.2: автореф. дис. … канд. мед. наук. — М.; 2014. — 26 с. [Kozlova YuO. Razrabotka tekhnologii pre- i postnatal’noi diagnostiki gruppy sindromov, obuslovlennykh mikrodeletsiei 22q11.2. [dissertation abstract] Moscow; 2014. 26 p. (In Russ).]Козлова Ю.О. Разработка технологии пре- и постнатальной диагностики группы синдромов, обусловленных микроделецией 22q11.2: автореф. дис. … канд. мед. наук. — М.; 2014. — 26 с. [Kozlova YuO. Razrabotka tekhnologii pre- i postnatal’noi diagnostiki gruppy sindromov, obuslovlennykh mikrodeletsiei 22q11.2. [dissertation abstract] Moscow; 2014. 26 p. (In Russ).]Weinzimer SA. Endocrine aspects of the 22q11.2 deletion syndrome. Genet Med. 2001;3(1):19–22. doi: 10.109700125817-200101000-00005.Weinzimer SA. Endocrine aspects of the 22q11.2 deletion syndrome. Genet Med. 2001;3(1):19–22. doi: 10.109700125817-200101000-00005.Garabedian M. Hypocalcemia and chromosome 22q11 microdeletion. Genet Couns. 1999;10(4):389–394.Garabedian M. Hypocalcemia and chromosome 22q11 microdeletion. Genet Couns. 1999;10(4):389–394.Choi JH, Shin YL, Kim GH, et al. Endocrine manifestations of chromosome 22q11.2 microdeletion syndrome. Horm Res. 2005; 63(6):294–299. doi: 10.1159/000086745.Choi JH, Shin YL, Kim GH, et al. Endocrine manifestations of chromosome 22q11.2 microdeletion syndrome. Horm Res. 2005; 63(6):294–299. doi: 10.1159/000086745.Cheung EN, et al. Prevalence of hypocalcemia and its associated features in 22q11.2 deletion syndrome. Clin Endocrinol (Oxf). 2014;81(2):190–196. doi: 10.1111/cen.12466.Cheung EN, et al. Prevalence of hypocalcemia and its associated features in 22q11.2 deletion syndrome. Clin Endocrinol (Oxf). 2014;81(2):190–196. doi: 10.1111/cen.12466.Taylor SC, Morris G, Wilson D, et al. Hypoparathyroidism and 22q11 deletion syndrome. Arch Dis Child. 2003;88(6):520–522. doi: 10.1136/adc.88.6.520.Taylor SC, Morris G, Wilson D, et al. Hypoparathyroidism and 22q11 deletion syndrome. Arch Dis Child. 2003;88(6):520–522. doi: 10.1136/adc.88.6.520.Fung WL, Butcher NJ, Costain G, et al. Practical guidelines for managing adults with 22q11.2 deletion syndrome. Genet Med. 2015;17(8):599–609. doi: 10.1038/gim.2014.Fung WL, Butcher NJ, Costain G, et al. Practical guidelines for managing adults with 22q11.2 deletion syndrome. Genet Med. 2015;17(8):599–609. doi: 10.1038/gim.2014.Piliero LM, Sanford AN, McDonald-McGinn DM, et al. T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome. Blood. 2004;103(3):1020–11025. doi: 10.1182/blood-2003-08-2824.Piliero LM, Sanford AN, McDonald-McGinn DM, et al. T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome. Blood. 2004;103(3):1020–11025. doi: 10.1182/blood-2003-08-2824.Jyonouchi S, McDonald-McGinn DM, Bale S, et al. CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness) syndrome and chromosome 22q11.2 deletion syndrome: a comparison of immunologic and nonimmunologic phenotypic features. Pediatrics. 2009;123(5):e871– e877. doi: 10.1542/peds.2008-3400.Jyonouchi S, McDonald-McGinn DM, Bale S, et al. CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness) syndrome and chromosome 22q11.2 deletion syndrome: a comparison of immunologic and nonimmunologic phenotypic features. Pediatrics. 2009;123(5):e871– e877. doi: 10.1542/peds.2008-3400.Sullivan KE, McDonald-McGinn D, Zackai EH. CD4(+) CD25(+) T-cell production in healthy humans and in patients with thymic hypoplasia. Clin Diagn Lab Immunol. 2002;9(5):1129– 1131. doi: 10.1128/CDLI.9.5.1129-1131.2002.Sullivan KE, McDonald-McGinn D, Zackai EH. CD4(+) CD25(+) T-cell production in healthy humans and in patients with thymic hypoplasia. Clin Diagn Lab Immunol. 2002;9(5):1129– 1131. doi: 10.1128/CDLI.9.5.1129-1131.2002.Zemble R, Luning Prak E, McDonald K, et al. Secondary immunologic consequences in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Immunol. 2010;136(3):409–418. doi: 10.1016/j.clim.2010.04.011.Zemble R, Luning Prak E, McDonald K, et al. Secondary immunologic consequences in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Immunol. 2010;136(3):409–418. doi: 10.1016/j.clim.2010.04.011.Sullivan KE, McDonald-McGinn DM, Driscoll DA, et al. Juvenile rheumatoid arthritis-like polyarthritis in chromosome 22q11.2 deletion syndrome (DiGeorge anomalad/velocardiofacial syndrome/conotruncal anomaly face syndrome). Arthritis Rheum. 1997;40(3):430–436. doi: 10.1002/art.1780400307.Sullivan KE, McDonald-McGinn DM, Driscoll DA, et al. Juvenile rheumatoid arthritis-like polyarthritis in chromosome 22q11.2 deletion syndrome (DiGeorge anomalad/velocardiofacial syndrome/conotruncal anomaly face syndrome). Arthritis Rheum. 1997;40(3):430–436. doi: 10.1002/art.1780400307.Lawrence S, McDonald-McGinn DM, Zackai E, Sullivan KE. Thrombocytopenia in patients with chromosome 22q11.2 deletion syndrome. J Pediatr. 2003;143(2):277–278. doi: 10.1067/S0022-3476(03)00248-8.Lawrence S, McDonald-McGinn DM, Zackai E, Sullivan KE. Thrombocytopenia in patients with chromosome 22q11.2 deletion syndrome. J Pediatr. 2003;143(2):277–278. doi: 10.1067/S0022-3476(03)00248-8.Becker DB, Pilgram T, Marty-Grames L, et al. Accuracy in identification of patients with 22q11.2 deletion by likely care providers using facial photographs. Plast Reconstr Surg. 2004;114(6): 1367–1372. doi: 10.1097/01.prs.0000138591.20999.f1.Becker DB, Pilgram T, Marty-Grames L, et al. Accuracy in identification of patients with 22q11.2 deletion by likely care providers using facial photographs. Plast Reconstr Surg. 2004;114(6): 1367–1372. doi: 10.1097/01.prs.0000138591.20999.f1.Greenhalgh KL, Aligianis IA, Bromilow G, et al. 22q11 deletion: a multisystem disorder requiring multidisciplinary input. Arch Dis Child. 2003;88(6):523–524. doi: 10.1136/adc.88.6.523.Greenhalgh KL, Aligianis IA, Bromilow G, et al. 22q11 deletion: a multisystem disorder requiring multidisciplinary input. Arch Dis Child. 2003;88(6):523–524. doi: 10.1136/adc.88.6.523.Digilio MC, Pacifico C, Tieri L, et al. Audiological findings in patients with microdeletion 22q11 (di George/velocardiofacial syndrome). Br J Audiol. 1999;33(5):329–333. doi: 10.3109/03005369909090116.Digilio MC, Pacifico C, Tieri L, et al. Audiological findings in patients with microdeletion 22q11 (di George/velocardiofacial syndrome). Br J Audiol. 1999;33(5):329–333. doi: 10.3109/03005369909090116.Ford LC, Sulprizio SL, Rasgon BM. Otolaryngological mani festations of velocardiofacial syndrome: a retrospective review of 35 patients. Laryngoscope. 2000;110(3 Pt 1):362–367. doi: 10.1097/00005537-200003000-00006.Ford LC, Sulprizio SL, Rasgon BM. Otolaryngological mani festations of velocardiofacial syndrome: a retrospective review of 35 patients. Laryngoscope. 2000;110(3 Pt 1):362–367. doi: 10.1097/00005537-200003000-00006.Stransky C, Basta M, McDonald-McGinn DM, et al. Perioperative risk factors in patients with 22q11.2 deletion syndrome requiring surgery for velopharyngeal dysfunction. Cleft Palate Craniofac J. 2015;52(2):183–191. doi: 10.1597/13-206.Stransky C, Basta M, McDonald-McGinn DM, et al. Perioperative risk factors in patients with 22q11.2 deletion syndrome requiring surgery for velopharyngeal dysfunction. Cleft Palate Craniofac J. 2015;52(2):183–191. doi: 10.1597/13-206.Schneider M, Debbane M, Bassett AS, et al. Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 deletion syndrome. Am J Psychiatry. 2014;171(6):627–639. doi: 10.1176/appi.ajp.2013.13070864.Schneider M, Debbane M, Bassett AS, et al. Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 deletion syndrome. Am J Psychiatry. 2014;171(6):627–639. doi: 10.1176/appi.ajp.2013.13070864.Green T, Gothelf D, Glaser B, et al. Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome. J Am Acad Child Adolesc Psychiatry. 2009;48(11):1060-1068. doi: 10.1097/CHI.0b013e3181b76683.Green T, Gothelf D, Glaser B, et al. Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome. J Am Acad Child Adolesc Psychiatry. 2009;48(11):1060-1068. doi: 10.1097/CHI.0b013e3181b76683.Antshel KM, Fremont W, Roizen NJ, et al. ADHD, major depressive disorder, and simple phobias are prevalent psychiatric conditions in youth with velocardiofacial syndrome. J Am Acad Child Adolesc Psychiatry. 2006;45(5):596–603. doi: 10.1097/01.chi.0000205703.25453.5a.Antshel KM, Fremont W, Roizen NJ, et al. ADHD, major depressive disorder, and simple phobias are prevalent psychiatric conditions in youth with velocardiofacial syndrome. J Am Acad Child Adolesc Psychiatry. 2006;45(5):596–603. doi: 10.1097/01.chi.0000205703.25453.5a.Campbell L, Swillen A. The cognitive spectrum in velo-cardiofacial syndrome. In: Murphy KC, Scramble PJ, editors. Velo-cardiofacial syndrome: a model for understanding microdeletion disorders. Cambridge, UK: Cambridge University Press; 2005. pp. 147–164. 57. Vorstman JA, Morcus ME, Duijff SN, et al. The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry. 2006;45(9): 1104–1113. doi: 10.1097/01.chi.0000228131.56956.c1.Campbell L, Swillen A. The cognitive spectrum in velo-cardiofacial syndrome. In: Murphy KC, Scramble PJ, editors. Velo-cardiofacial syndrome: a model for understanding microdeletion disorders. Cambridge, UK: Cambridge University Press; 2005. pp. 147–164. 57. Vorstman JA, Morcus ME, Duijff SN, et al. The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry. 2006;45(9): 1104–1113. doi: 10.1097/01.chi.0000228131.56956.c1.Bassett AS, Chow EW, AbdelMalik P, et al. The schizophrenia phenotype in 22q11 deletion syndrome. Am J Psychiatry. 2003; 160(9):1580–1586. doi: 10.1176/appi.ajp.160.9.1580.Bassett AS, Chow EW, AbdelMalik P, et al. The schizophrenia phenotype in 22q11 deletion syndrome. Am J Psychiatry. 2003; 160(9):1580–1586. doi: 10.1176/appi.ajp.160.9.1580.Beaton EA, Simon TJ. How might stress contribute to increased risk for schizophrenia in children with chromosome 22q11.2 deletion syndrome? J Neurodev Disord. 2011;3(1):68– 75. doi:10.1007/s11689-010-9069-9.Beaton EA, Simon TJ. How might stress contribute to increased risk for schizophrenia in children with chromosome 22q11.2 deletion syndrome? J Neurodev Disord. 2011;3(1):68– 75. doi:10.1007/s11689-010-9069-9.Glaser B, Mumme DL, Blasey C, et al. Language skills in children with velocardiofacial syndrome (deletion 22q11.2). J Pediatr. 2002; 140(6):753–758. doi: 10.1067/mpd.2002.124774.Glaser B, Mumme DL, Blasey C, et al. Language skills in children with velocardiofacial syndrome (deletion 22q11.2). J Pediatr. 2002; 140(6):753–758. doi: 10.1067/mpd.2002.124774.Gerdes M, Solot C, Wang PP, et al. Cognitive and behavior profile of preschool children with chromosome 22q11.2 deletion. Am J Med Genet. 1999;85(2):127–133. doi: 10.1002/(sici)1096-8628(19990716)85:2<127::aid-ajmg6>3.3.co;2-6.Gerdes M, Solot C, Wang PP, et al. Cognitive and behavior profile of preschool children with chromosome 22q11.2 deletion. Am J Med Genet. 1999;85(2):127–133. doi: 10.1002/(sici)1096-8628(19990716)85:2<127::aid-ajmg6>3.3.co;2-6.Mills L, Gosling A, Sell D. Extending the communication phenotype associated with 22q11.2 microdeletion syndrome. Advances in Speech Language Pathology. 2006;8(1):17– 27. doi: 10.1080/14417040500459650.Mills L, Gosling A, Sell D. Extending the communication phenotype associated with 22q11.2 microdeletion syndrome. Advances in Speech Language Pathology. 2006;8(1):17– 27. doi: 10.1080/14417040500459650.Kiley-Brabeck K, Sobin C. Social skills and executive function deficits in children with the 22q11 Deletion Syndrome. Appl Neuropsychol. 2006;13(4):258–268. doi: 10.1207/s15324826an1304_7.Kiley-Brabeck K, Sobin C. Social skills and executive function deficits in children with the 22q11 Deletion Syndrome. Appl Neuropsychol. 2006;13(4):258–268. doi: 10.1207/s15324826an1304_7.McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore). 2011;90(1):1–18. doi: 10.1097/MD.0b013e3182060469.McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore). 2011;90(1):1–18. doi: 10.1097/MD.0b013e3182060469.Forbes BJ, Binenbaum G, Edmond JC, et al. Ocular findings in the chromosome 22q11.2 deletion syndrome. J AAPOS. 2007; 11(2):179–182. doi: 10.1016/j.jaapos.2006.08.006.Forbes BJ, Binenbaum G, Edmond JC, et al. Ocular findings in the chromosome 22q11.2 deletion syndrome. J AAPOS. 2007; 11(2):179–182. doi: 10.1016/j.jaapos.2006.08.006.Wu HY, Rusnack SL, Bellah RD, et al. Genitourinary malformations in chromosome 22q11.2 deletion. J Urol. 2002;168(6):2564–2565. doi: 10.1097/01.ju.0000032176.07703.23.Wu HY, Rusnack SL, Bellah RD, et al. Genitourinary malformations in chromosome 22q11.2 deletion. J Urol. 2002;168(6):2564–2565. doi: 10.1097/01.ju.0000032176.07703.23.

The authors declare that there are no conflicts of interest present.