Summary
The DiGeorge anomaly, originally considered a clinical paradigm for isolated thymus deficiency, has now been redefined as a member of a group of disorders that share in common a chromosome deletion resulting in monosomy 22q11 (CATCH-22 or DGA/VCFS). In addition to the thymus defect, conotruncal heart anomalies, dysmorphism, hypoparathyroidism, and cleft palate are prominent features. Despite the emphasis on thymus involvement in DGA, a clinically significant thymus defect is found only in a small percentage of these patients problably occurring in less than 5% of the cases. Maldescent of the thymus, however, is extremely common, leading to an absence of mediastinal thymic tissue in nearly all cases.
The basic embryological fault in these disorders is an inadequate development of the facial neural-crest tissues, resulting in defective organogenesis of pharyngeal pouch derivatives that receive cephalic neural-crest contribution to the mesenchmyme. The causes for this maldevelopment are both genetic and extragenetic in origin and the genetic lesions act in concert with random environmental events to produce the ultimate clinical picture.
The modern research approaches now available have cleared away most of the confusion clouding the clinical and theoretical aspects of DGA and related disorders, providing the clinician with useful landmarks to assess and treat these intriguing clinical challenges.
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References
Cooper, M. D., Peterson, R. D. A., and Good, R. A. (1966), Nature 205, 143–146.
Miller, J. F. A. P. (1961), Lancet ii, 748–749.
Archer, O. K. and Pierce, J. C. (1961), Fed. Proc. 20, 751–763.
DiGeorge, A. M. (1965), J. Pediatr. 67, 907.
Belohradsky, B. H. (1985), Ergeb. Inn. Med. Kinderheilkd. 54, 36–105.
Conley, M. E., Beckwith, J. B., Mancer, J. F. K., and Tenckhoff, L. (1979), J. Pediatr. 94, 883–890.
DiGeorge, A. M. (1968), in Birth Defects Original Article Series IV, Bergsma, D., ed., The National Foundation, New York, NY, pp. 116–121.
De la Chapelle, A., Herva, R., Koivisto, M., and Aula, P. (1981), Hum. Genet. 57, 253–256.
Shprintzen, R. J., Goldberg, R. B., Young, D., and Wolford, L. (1981), Pediatr. 67, 167–172.
Kinouchi, A., Mori, K., Ando, M., and Takao, A. (1976), Pediatr. Jpn. 17, 84.
Wilson, D. I., Burn, J., Scambler, P., and Goodship, J. (1993), J. Med. Genet. 30, 852–856.
Goldmuntz, E. and Emanuel, B. S. (1997), Circ. Res. 80, 437–443.
Greenberg, F. (1993), J. Med. Genet. 30, 803–806.
Levy-Mozziconacci, A., Wernert, F., Scambler, P. Rouault, F., Metras, D., Kreitman, B., et al. (1994), Eur. J. Pediatr. 153, 813–820.
Demczuk, S. and Aurias, A. (1995), Ann. Genet. 38, 59–76.
Ryan, A. K., Godship, J. A., Wilson, D. I., Philip, N., Levy, A., Seidel, H., et al. (1997), 34, J. Med. Genet. 798–804.
Lammer, E. J. and Opitz, J. M. (1986), Am. J. Med. Genet. 2, 113–127.
Le Douarin, N. M. (1986), Ann. NY Acad. Sci. 486, 66–86.
Bockman, D. E. and Kirby, M. L. (1984), Science 223, 498–500.
Kalter, H. and Warkany, J. (1961), Am. J. Pathol. 38, 1–21.
Johnson, S., Knight, R., Marmer, D. J., and Steele, R. W. (1981), Pediatr. Res. 15, 908–911.
Ammann, A. J., Wara, D. W., Barrett, D. J., and Stiehm, E. R. (1982), Am. J. Dis. Child. 136, 906–908.
Okishima, T., Eizuru, Y., Minamishima, Y., Ohdo, S., and Hayakawa, K. (1984), Cong. Anom. 25, 29–44.
Oster, G., Kilburn, H. H., and Siegal, F. P. (1983), Clin. Immunol. Immunopathol. 28,128–134.
Carey, A. H., Roach, S., Williamson, R., Dumanski, J. P., Nordenskjold, M., Collins, V. P., et al. (1990), Genomics 7, 1–8.
Fibison, W. J., Budarf, M., McDermid, H., Greenberg, F., and Emanuel, B. (1990), Am. J. Hum. Genet. 46, 888–895.
Kelly, D., Goldberg, R., Wilson, D., Lindsay, E., Carey, A., Goodship, J., et al. (1993), Am. J. Med. Genet. 45, 308–312.
Augusseau, S., Jouk, S., Jalbert, P., and Prieur, M. (1986), Hum. Genet. 74, 206, 207.
Lindsay, E. A., Halford, S., Wadey, R., Scambler, P. J., and Baldini, A. (1993), Genomics 17, 403–407.
Thompson, P. W. and Davies, S. J. (1998), J. Med. Genet. 35, 789 (letter).
Budarf, M. L. and Emanuel, B. S. (1997), Hum. Mol. Genet. 6, 1657–1665.
Dallipicola, B., Pizzuti, A., and Novelli, G. (1996), Am. J. Hum. Genet. 59, 70, 71.
Gottlieb, S., Hanes, S. D., Golden, J. A., Oakey, R. J., and Budarf, M. L. (1998), Hum. Mol. Genet. 7, 1497–1505.
Wilming, L. G., Snoeren, A. S., Van Rijswink, A., Grosveld, F., and Meijers, C. (1997), Hum. Mol. Genet. 6, 247–259.
Gottlieb, S., Emanuel, B. S., Driscoll, D. A., Sellinger, B., Wang, Z., Roe, R., and Budarf, M. L. (1997), Am. J. Hum. Genet. 60, 1194–1201.
Lorain, S., Quivy, J-P., Monier-Gavelle, F., Scamps, C., Lecluse, Y., Almouzni, G., and Lipinski, M. (1998), Mol. Cell. Biol. 18, 5546–5556.
Tsui, K. M., Ng, Y. Y., and Lam, T. S. (1997), Acta Paediat. Sinica 38, 52–56.
Goodship, J., Cross, I., Scambler, P., and Burn, J. (1995), J. Med. Genet. 32, 746–748.
Greenberg, F., Elder, F. F. B., Haffner, P., Northrup, H., and Ledbetter, D. H., Am. J. Hum. Genet. 43, 605–611.
Greenberg, F., Courtney K. B., Wessels, R. A., Huhta, J., Carpenter, R. J., Rich, D. C., and Ledbetter, D. H. (1988), Am. J. Med. Genet. 31, 1–4.
Schuffenhauer, S., Seidel, H., Oechsler, H., Belohradsky, B., Bernsan, U., Murken, J., and Meitinger, T. (1995), Ann. Genet. 38, 162–167.
Gottlieb, S., Driscoll, D. A., Punnett, H. H., Sellinger, B., Emanuel, B. S., and Budarf, M. L. (1998), Am. J. Hum. Genet. 62, 495–498.
Bale, P. M. and Sotelo-Avila, C. (1993), Pediatr. Pathol. 13, 181–190.
Junker, A. K. and Driscoll, D. A. (1995), J.Pediatr. 127, 231–237.
Bastian, J., Law, S., Vogler, L., Lawton, A., Herrod, H., Anderson, S., et al. (1989), J. Pediatr. 115, 391–396.
Borzy, M. S., Schulte-Wisserman, H., Gilbert, E., Horowitz, S. D., Pellett, J., and Hong, R. (1979), Clin. Immunol. Immunopathol. 12, 31–51.
Gupta, S., Aggarwal, S., and Nguyen, T. (1998), Clin. Exp. Immunol. 113, 65–71.
Haire, R. N., Buell, R. D., Litman, R. T., Ohta, Y., Fu, S. M., Honjo, T., et al. (1993), J. Exp. Med. 178, 825–834.
Hong, R. (1998), Sem. Hematol. 35, 282–290.
DiGeorge, A.M. (1987), Nelson Textbook of Pediatrics in Behrman, R. E., Vaughan, V. C., and Nelson, W. C., eds., W. B. Saunders, Philadelphia, pp. 1208–1211.
Gidding, S. S., Minciotti, A. L., and Langman, C. B. (1988), N. Engl. J. Med. 319, 1589–1591.
McCune, J. M., Loftus, R., Schmidt, D. K., Carroll, P., Webster, D., Swor-Yim, L. B., et al. (1998), J. Clin. Invest. 101, 2301–2308.
Muller, W., Peter, H. H., Kallfelz, H. C., Franz, A., and Rieger, C. H. L. (1989), Eur. J. Pediatr. 149, 96–103.
Lane, H. C., Depper, J. M., Greene, W. C., Whalen, G., and Waldmann, T. A. (1985), N. Engl. J. Med. 313, 79–84.
Archer, E., Chuang, T-Y., and Hong, R. (1990), Cutis 45, 455–459.
Markert, M. L., Hummell, D. S., Rosenblatt, H. M., Schiff, S. E., Harville, T. O., Williams, L. W., et al. (1998), J. Pediatr. 132, 15–21.
Lischner, H. W., and DiGeorge, A. M. (1969), Lancet ii, 1044–1049.
Durandy, A., LeDiest, F., Fischer, A., and Griscelli, C. (1968), J. Clin. Immunol. 6, 265–270.
Kourtis, A. P., Ibegbu, C. C., Lee, F. K., Vogler, L., Philips, K., and Nahmias, A. J. (1997), Scand. J. Immunol. 46, 281–283.
Cuneo, B. F., Langman, C. B., Ilbawi, M. N., Ramakrishnan, V., Cutilletta, A., and Driscoll, D. A. (1996), Circulation 93, 1702–1708.
Wells, T. R., Gilsanz, V., Senac, M. O., Landing, B. H., Vachon, L., and Takahashi, M. (1986), Br. J. Radiol. 59, 1065–1068.
Burke, B. A., Johnson, D., Gilbert, E. F., Drut, R. M., Ludwig, J., and Wick, M. R. (1987), Hum. Pathol. 18, 355–360.
Stiehm, E. R. (1989), 1989, Immunologic Disorders in Infants and Children in Stiehm, E. R., ed., WB Saunders, Philadelphia, pp 157–195.
Devriendt, K., Fryns, J-P., Mortier, G. A., Van Thienen, M-N., and Keymolen, K. (1998), J. Med. Genet. 35, 789, 790 (letter).
Goldmuntz, E., Clark, B. J., Mitchell, L. E., Jawad, A. F., Cuneo, B. F., Reed, L. et al. (1998), J. Am. Coll. Cardiol. 32, 492–498.
Rohn, R. D., Leffell, M. S., Leadem, P., Johnson, D., Rubio, T., and Emanuel, B. S. (1984), J. Pediatr. 105, 47–51.
Keppen, L. D., Fasules, J. W., Burks, A. W., Gollin, S. M., Sawyer, J. R., and Miller, C. H. (1988), J. Pediatr. 113, 506–508.
Maaswinkel-Mooij, P. D., Papapoulos, S. E., Gerritsen, E. J. A., Muddle, A. H., and Van de Kamp, J. J. P. (1989), Eur. J. Pediatr. 149, 179–183.
Tuvia, J., Weisselberg, B., Shif, I., and Keren, G. (1988), Eur. J. Pediatr. 147, 643, 644.
Kretschmer, R., Say, B., Brown, D., and Rosen, F. S. (1968), N. Engl. J. Med. 279, 1295–1301.
Ham Pong, A. J., Cavallo, A., Holman, G. H., and Goldman, A. S. (1985), J. Pediatr. 106, 619, 620.
Sullivan, K. E., McDonald-McGinn, D. M., Driscoll, D. A., Zmijewski, C. M., Ellabban, A. S., Reed, L., et al. (1997), Arthritis. Rheum. 40, 430–436.
August, C. S., Rosen, F. S., Filler, R. M., Janeway, C. A., Markowski, B., and Kay, H. E. M. (1968), Lancet 2, 1210, 1211.
Barrett, D. J., Wara, D. W., Ammann, A. J., and Cowan, M. J. (1980), J. Pediatr. 97, 66–71.
Cleveland, W. W., Fogel, B. J., Brown, W. T., and Kay, H. E. M. (1968), Lancet 2, 1211–1214.
Markert, M. L., Kostyu, D. D., Ward, F. E., McLaughlin, T. M., Watson, T. J., Buckley, R. H., et al. (1997), J. Immunol. 158, 998–1005.
Thong, Y. H., Robertson, E. R., Rischbieth, H. G., Smith, G. J., Binns, G. F., Cheney, K., and Pollard, A. C. (1978), Arch. Dis. Child. 53, 580–584.
Goldsobel, A. B., Haas, A., and Stiehm, E. R. (1987), J. Pediatr. 111, 40–44.
Borzy, M. S., Ridgway, D., Noya, F. J., and Shearer, W. T. (1989), J. Clin. Immunol. 9, 386–392.
Matsumoto, T., Amamato, N., Kondo, T., Nakayama, M., Takayanagi, T., and Tsuji, Y. (1998), Bone Marrow Transplant. (1998), 22, 927–930.
Bowers, D. C., Lederman, H. M., Sicherer, S. H., Winkelstein, J. A., and Chen, A. R. (1998), Lancet 352, 1983, 1984.
Reisner, Y., Kapoor, N., Kirkpatrick, D., Pollack, M. S., Cunningham-Rundles, S., Dupont, B., et al. (1983), Blood 61, 341–348.
Fischer, A., Durandy, A., De Villartay, J-P., Vilmer, E., Le Diest, F., Geruta, I., and Griscelli, C. (1986), Blood 67, 444–449.
Moen, R. C., Horowitz, S. D., Sondel, P. M., Borcherding, W. R., Trigg, M. E., Billing, R. E., and Hong, R. (1987), Blood 70, 664–669.
Filipovitch, A. H., Shapiro, R. S., Ramsay, N. K. C., Kim, T., Blazar, B., Kersey, J., and McGlave, P. (1992), Blood 80, 270–276.
Rubenstein, P., Carrier, C., Scaradavon, A., Kurtzberg, J., Adamson, J., Migliaccio, A. R., et al. (1998), N. Engl. J. Med. 339, 1565–1577.
Bristow, J. D. and Bernstein, H. S. (1998), J. Am. Coll. Cardiol. 32, 499–501.
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Hong, R. The DiGeorge anomaly. Clinic Rev Allerg Immunol 20, 43–60 (2001). https://doi.org/10.1385/CRIAI:20:1:43
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DOI: https://doi.org/10.1385/CRIAI:20:1:43