DiGeorge综合征

多达60%的患者有低钙血症，低钙癫痫常见。[49]Ryan AK, Goodship JA, Wilson DI, et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet. 1997;34:798-804.http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1051084&blobtype=pdfhttp://www.ncbi.nlm.nih.gov/pubmed/9350810?tool=bestpractice.com患者均应筛查血清钙及全段PTH水平。随着孩子年龄增长，低钙血症的问题逐渐淡化。[49]Ryan AK, Goodship JA, Wilson DI, et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet. 1997;34:798-804.http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1051084&blobtype=pdfhttp://www.ncbi.nlm.nih.gov/pubmed/9350810?tool=bestpractice.com

甲状旁腺功能减低

大约80%患儿有先天性心脏病。[39]Marino B, Digilio MC, Toscano A, et al. Anatomic patterns of conotruncal defects associated with deletion 22q11. Genet Med. 2001;3:45-48.http://www.ncbi.nlm.nih.gov/pubmed/11339377?tool=bestpractice.com圆锥动脉干畸形例如主动脉弓离断B型及共同动脉干是最具特征性的，但法洛四联症、室间隔缺损及其他心脏畸形同样常见。[98]Goldmuntz E, Clark BJ, Mitchell LE, et al. Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol. 1998:32;492-498.http://www.ncbi.nlm.nih.gov/pubmed/9708481?tool=bestpractice.com[99]Van Mierop LH, Kutsche LM. Cardiovascular anomalies in DiGeorge syndrome and importance of neural crest as a possible pathogenetic factor. Am J Cardiol. 1986;58:133-137.http://www.ncbi.nlm.nih.gov/pubmed/3728313?tool=bestpractice.com

腭部疾病最常见的是腭咽闭合不全，导致鼻音及发音不清。[51]Goldberg R, Motzkin B, Marion R, et al. Velo-cardio-facial syndrome: a review of 120 patients. Am J Med Genet. 1993;45:313-319.http://www.ncbi.nlm.nih.gov/pubmed/8434617?tool=bestpractice.com[52]Zori RT, Boyar FZ, Williams NW, et al. Prevalence of 22q11 region deletions in patients with velopharyngeal insufficiency. Am J Med Genet. 1998;77:8-11.http://www.ncbi.nlm.nih.gov/pubmed/9557885?tool=bestpractice.com语言治疗可能会有帮助，但一些患儿需要手术治疗。通常，其他患儿的手术效果不如22qDS显著。腭裂及黏膜下裂发生于20%的儿童，可通过常规手术方式治疗。

唇腭裂

四分之三的患儿有至少一种牙齿异常，多数是下颌第一前磨牙发育不良或牙釉质浑浊。[106]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;106:e46-e51.http://www.ncbi.nlm.nih.gov/pubmed/18554940?tool=bestpractice.com有腭裂者还可有与之相关的其他牙齿问题。牙齿发育不全和多生牙与22qDS无关。

患儿有患精神分裂症、双向情感障碍和抑郁症风险。[55]Bassett AS, Chow EW. 22q11 deletion syndrome: a genetic subtype of schizophrenia. Biol Psychiatry. 1999;46:882-891.http://www.ncbi.nlm.nih.gov/pubmed/10509171?tool=bestpractice.com22qDS人群中精神分裂症风险可高达20%。

精神分裂症

一项关于22qDS听力损失的研究证实高频感音神经性或混合型听力丧失常见。携带有COMTMet等位基因的儿童受影响程度小，提示该修饰基因具有保护作用。[110]Zarchi O, Attias J, Raveh E, et al. A comparative study of hearing loss in two microdeletion syndromes: velocardiofacial (22q11.2 deletion) and Williams (7q11.23 deletion) syndromes. J Pediatr. 2011;158:301-306.http://www.ncbi.nlm.nih.gov/pubmed/20846670?tool=bestpractice.com

听力损失评估

同其他染色体改变导致的疾病一样，高达20%患儿有某种类型的甲状腺疾病。[100]Bassett AS, Chow EW, Husted J, et al. Clinical features of 78 adults with 22q11 deletion syndrome. Am J Med Genet A. 2005;138A:307-313.http://www.ncbi.nlm.nih.gov/pubmed/16208694?tool=bestpractice.com桥本氏甲状腺炎及Graves病已被观察到。[101]Choi JH, Shin YL, Kim GH, et al. Endocrine manifestations of chromosome 22q11.2 microdeletion syndrome. Horm Res. 2005;63:294-299.http://www.ncbi.nlm.nih.gov/pubmed/15995343?tool=bestpractice.com高达46%患儿可见更多甲状腺微小异常。[102]Stagi S, Lapi E, Gambineri E, et al. Thyroid function and morphology in subjects with microdeletion of chromosome 22q11 (del(22)(q11)). Clin Endocrinol (Oxf). 2010;72:839-844.http://www.ncbi.nlm.nih.gov/pubmed/19863572?tool=bestpractice.com

原发性甲状腺功能减退

呼吸道病毒感染的几率增加。[58]Kobrynski LJ, Sullivan KE. Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet. 2007;370:1443-1452.http://www.ncbi.nlm.nih.gov/pubmed/17950858?tool=bestpractice.com不论是否存在免疫缺陷均会发生。细菌感染应及时给予适当抗生素治疗。

胃食管反流病常见并可能导致喂养困难。[105]Rommel N, Vantrappen G, Swillen A, et al. Retrospective analysis of feeding and speech disorders in 50 patients with velo-cardio-facial syndrome. Genet Couns. 1999;10:71-78.http://www.ncbi.nlm.nih.gov/pubmed/10191432?tool=bestpractice.com反流可通过PH探针被诊断。患儿除普通治疗外，需要更多重要的干预措施以控制症状，包括胃底折叠术。

婴儿喂养障碍

过敏常见于22q11.2缺失。这可能由于胸腺产生T细胞减少，迫使T细胞稳态增殖，导致T细胞和B细胞功能异常所致。这些增殖的T细胞更可能为Th2表型，因此有助于引起过敏反应。[107]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;136:409-418.http://www.ncbi.nlm.nih.gov/pubmed/20472505?tool=bestpractice.com

多达70%患儿有角膜后胚胎环和视网膜血管异常，虽然这通常不影响视力。[109]Mansour AM, Goldberg RB, Wang FM, et al. Ocular findings in the velo-cardio-facial syndrome. J Pediatr Ophthalmol Strabismus. 1987;24:263-266.http://www.ncbi.nlm.nih.gov/pubmed/3681616?tool=bestpractice.com

虽然大多数婴幼儿可见某种程度T细胞减少，显著的T细胞缺陷不常见。[59]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;103:1020-1025.http://www.bloodjournal.org/content/103/3/1020.long?sso-checked=truehttp://www.ncbi.nlm.nih.gov/pubmed/14525774?tool=bestpractice.com所有患儿均应通过流式细胞仪测定T细胞计数以确定是否进行免疫重建。预防性应用甲氧苄啶/磺胺甲基异恶唑及避免接种活病毒疫苗往往是不必要的，除非存在T细胞缺陷（T细胞计数<600个/mm^3)和/或准备进行免疫重建。[82]Moylett EH, Wasan AN, Noroski LM, et al. Live viral vaccines in patients with partial DiGeorge syndrome: clinical experience and cellular immunity. Clin Immunol. 2004;112:106-112.http://www.ncbi.nlm.nih.gov/pubmed/15207787?tool=bestpractice.com[83]Perez EE, Bokszczanin A, McDonald-McGinn D, et al. Safety of live viral vaccines in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Pediatrics. 2003;112:e325.http://pediatrics.aappublications.org/cgi/content/full/112/4/e325http://www.ncbi.nlm.nih.gov/pubmed/14523220?tool=bestpractice.com[84]Chinen J, Rosenblatt HM, Smith EO, et al. Long-term assessment of T-cell populations in DiGeorge syndrome. J Allergy Clin Immunol. 2003;111:573-579.http://www.ncbi.nlm.nih.gov/pubmed/12642839?tool=bestpractice.com[85]Davis CM, Kancherla VS, Reddy A, et al. Development of specific T-cell responses to Candida and tetanus antigens in partial DiGeorge syndrome. J Allergy Clin Immunol. 2008;122:1194-1199.http://www.ncbi.nlm.nih.gov/pubmed/18789819?tool=bestpractice.com[86]Azzari C, Gamineri E, Resti M, et al. Safety and immunogenicity of measles-mumps-rubella vaccine in children with congenital immunodeficiency (DiGeorge syndrome). Vaccine. 2005;23:1668-1671.http://www.ncbi.nlm.nih.gov/pubmed/15705470?tool=bestpractice.com[87]Sullivan KE. Live viral vaccines in patients with DiGeorge syndrome. Clin Immunol. 2004;113:3.http://www.ncbi.nlm.nih.gov/pubmed/15380522?tool=bestpractice.com[103]Al-Sukaiti N, Reid B, Lavi S, et al. Safety and efficacy of measles, mumps, and rubella vaccine in patients with DiGeorge syndrome. J Allergy Clin Immunol. 2010;126:868-869.http://www.ncbi.nlm.nih.gov/pubmed/20810153?tool=bestpractice.com虽然缺乏大样本病例研究，目前数据提示当T细胞计数>600个/mm^3时接种活疫苗是安全的。检测淋巴细胞增殖反应也有助于鉴别是否需要免疫重建。

重症联合免疫缺陷

大约10%的患儿发生自身免疫性疾病。幼年特发性关节炎是最常见的，但血细胞减少、糖尿病和甲状腺疾病也可发生。[104]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;40:430-436.http://www.ncbi.nlm.nih.gov/pubmed/9082929?tool=bestpractice.com这些并发症是不可预测的，一旦发生给予常规方式治疗。

血小板计数比健康对照组低，但是这一发现似乎没有临床意义，且临床上血小板计数无显著缺乏。[108]Lawrence S, McDonald-McGinn DM, Zackai E, et al. Thrombocytopenia in patients with chromosome 22q11.2 deletion syndrome. 2003;143:277-278.http://www.ncbi.nlm.nih.gov/pubmed/12970648?tool=bestpractice.com对于血小板减少症不需要特殊管理。

血小板减少症的评估