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11 - Genetic counseling

Published online by Cambridge University Press:  11 August 2009

By
Donna M. McDonald-McGinn  and
Elaine H. Zackai
Edited by
Kieran C. Murphy  and
Peter J. Scambler
Elaine H. Zackai
Affiliation:
22q and You Center, The Children's Hospital of Philadelphia, PA, USA
Kieran C. Murphy
Affiliation:
Education and Research Centre, Royal College of Surgeons of Ireland
Peter J. Scambler
Affiliation:
Institute of Child Health, University College London
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Summary

The 22q11.2 deletion has been identified in the majority of patients with DiGeorge syndrome (de la Chapelle et al., 1981; Kelley et al., 1982; Scambler et al., 1991; Driscoll et al., 1992a), velo-cardio-facial syndrome (VCFS) (Driscoll et al., 1992b, 1993) and conotruncal anomaly face syndrome (Burn et al., 1993; Matsouka et al., 1994) and in some patients with autosomal dominant Opitz G/BBB syndrome (McDonald-McGinn et al., 1995; Fryburg et al., 1996; LaCassie & Arriaza, 1996) and Cayler cardiofacial syndrome (Giannotti et al., 1994; Bawle et al., 1998). These diagnoses were originally described as individual entities by a number of subspecialists who were concentrating on one particular area of interest. For example, Dr. Angelo DiGeorge, an endocrinologist, first reported the combination of hypoparathyroidism and immune deficiency in children and this syndrome later came to bear his name. However, those syndromes are now collectively referred to by their chromosomal etiology – the 22q11.2 deletion. This phenomenon was previously likened to the old adage of a group of nearsighted veterinarians trying to identify an elephant by each examining a separate part (Figure 11.1). Each person was accurate in describing his own area of interest, but none was able to see the big picture. So too is the case with the 22q11.2 deletion. It was not until Fluorescence in situ hybridization (FISH) studies were available and we could identify a submicroscopic deletion in these patients that the etiology of the previously described separate entities was elucidated.

Keywords

22q11.2 deletionanatomic abnormalitycontiguous deletion syndromeDiGeorge syndrome, BBB syndromegenetic counselinggenetic inheritance
Type
Chapter
Information
Velo-Cardio-Facial Syndrome
A Model for Understanding Microdeletion Disorders
 , pp. 200 - 218
Publisher: Cambridge University Press
Print publication year: 2005

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References

Bawle, E. V., Conard, J., Dyke, D. L.et al. (1998) Letter to the Editor: seven new cases of Cayler cardiofacial syndrome with chromosome 22q11.2 deletion, including a familial case. Am. J. Med. Genet., 79, 406–10.Google Scholar
Bergoffen, J., Punnett, H., Campbell, T. J.et al. (1993) Diaphragmatic hernia in tetrasomy 12p mosaicism. J. Pediatr., 122 (4), 603–6.Google Scholar
Burn, J., Takao, A., Wilson, D.et al. (1993) Conotruncal anomaly face syndrome is associated with a deletion within chromosome 22. J. Med. Genet., 30, 822–4.Google Scholar
Consegave, M. W., Seip, J. R., Belchis, D. A.et al. (1996) Association of a mosaic chromosomal 22q11 deletion with hypoplastic left heart syndrome. Am. J. Cardiol., 77, 1023–5.Google Scholar
Cormier-Daire, V., Iserin, L., Theophile, D.et al. (1995) Upper limb malformations in DiGeorge syndrome. Am. J. Med. Genet., 56, 39–41.Google Scholar
Chapelle, A., Herva, R., Koivisto, M.et al. (1981) A deletion in chromosome 22 can cause DiGeorge syndrome. Hum. Genet., 57, 253–6.Google Scholar
Devriendt, K., Swillen, A., Fryns, J. P.et al. (1996) Renal and urological tract malformations caused by a 22q11 deletion. J. Med. Genet., 33, 349.Google Scholar
Devriendt, K., Smet, L., Boeck, K.et al. (1997) DiGeorge syndrome and unilateral symbrachydactyly. Genet. Counsec., 8, 345–7.Google Scholar
Digilio, M. C., Giannotti, A., Marino, B.et al. (1997) Radial aplasia and chromosome 22q11 deletion. J. Med. Genet., 34, 942–4.Google Scholar
Driscoll, D. A., Budarf, M. L. & Emanuel, B. S. (1992a) A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11. Am. J. Hum. Genet., 50, 924–33.Google Scholar
Driscoll, D. A., Spinner, N. B., Budarf, M. L.et al. (1992b) Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome. Am. J. Med. Genet., 44, 261–8.Google Scholar
Driscoll, D. A., Salvin, J., Sellinger, B.et al. (1993) Prevalence of 22q11 microdeletions in DGS and VCFS: implications for genetic counseling and prenatal diagnosis. J. Med. Genet., 30, 813–17.Google Scholar
Driscoll, D. A., Chen, P., Li, M.et al. (1995a) Familial 22q11 deletions: phenotypic variability and determination of deletion boundaries by FISH. Am. J. Hum. Genet., 57, 92 (abstr).Google Scholar
Driscoll, D. A., Randall, P., McDonald-McGinn, D. M. et al. (1995b) Are 22q11.2 chromosomal deletions a major cause of isolated cleft palate? 52nd Annual Meeting, American Cleft Palate-Craniofacial Association, Tampa, FL.
Edelman, L., Pandita, R. K. & Morrow, B. E. (1999) Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome. Am. J. Hum. Genet., 64, 1076–86.Google Scholar
Eicher, P. S., McDonald-McGinn, D. M., Fox, C. A.et al. (2000) Dysphagia in children with a 22q11.2 deletion: unusual pattern found on modified barium swallow. J. Pediatr., 137 (2), 158–64.Google Scholar
Emanuel, B. S., Budarf, M. L., Shaikh, T., et al. (1998) Blocks of duplicated sequence define the endpoints of DGS/VCFS 22q11.2 deletions. Am. J. Hum. Genet., 63, A11(abstr).Google Scholar
Fraser, F. C. (1980) The genetics of cleft lip and palate: Yet another look. In Pratt, R. M. & Christiansen, R. L., eds., Current Research Trends in Prenatal Craniofacial Development. Amsterdam: Elsevier Publishers.
Freeman, S. B., Taft, L. F., Dooley, K. J.et al. (1998) Population-based study of congenital heart defects in Down syndrome. Am. J. Med. Genet., 80 (3), 213–17.Google Scholar
Fryburg, J. S., Lin, K. Y. & Golden, E. F. (1996) Chromosome 22q11.2 deletion in a boy with Opitz oculo-genito-laryngeal syndrome. Am. J. Med. Genet., 62, 274–5.Google Scholar
Gerdes, M., Solot, C., Wang, P. P.et al. (1999) Cognitive and behavioral profile of preschool children with chromosome 22q11.2 microdeletion. Am. J. Med. Genet., 85 (2), 127–33.Google Scholar
Giannotti, A., Diglio, M. C., Marino, B.et al. (1994) Cayler cardiofacial syndrome and del 22q11: part of the CATCH22 phenotype. Am. J. Med. Genet., 30, 807–12.Google Scholar
Goldmuntz, E., Clark, B. J., Mitchell, L. E.et al. (1998) Frequency of 22q11 deletions in patients with conotruncal defects. J. Am. Coll. Cardiol., 32, 492–8.Google Scholar
Gripp, K. W., McDonald-McGinn, D. M., Driscoll, D. A.et al. (1997) Nasal dimple as part of the 22q11.2 deletion syndrome. Am. J. Med. Genet., 69, 290–2.Google Scholar
Hatchwell, E., Long, F., Wilde, J.et al. (1998) Molecular confirmation of germ line mosaicism for a submicroscopic deletion of chromosome 22q11. Am. J. Med. Genet., 78, 103–6.Google Scholar
Kawame, H., Adachi, M., Tachibana, K.et al. (2001) Graves' disease in patients with 22q11.2 deletion. J. Pediatr., 139 (6), 892–5.Google Scholar
Keenan, G. F., Sullivan, K. E., McDonald-McGinn, D. M.et al. (1997) Letter to the editor: arthritis associated with 22q11.2: more common than previously suspected. Am. J. Med. Genet., 71, 488.Google Scholar
Kelley, R. I., Zackai, E. H., Emanuel, B. S.et al. (1982) The association of the DiGeorge anomalad with partial monosomy of chromosome 22. J. Pediatr., 101, 197–200.Google Scholar
LaCassie, Y. & Arriaza, M. I. (1996) Letter to the Editor: Opitz GBBB syndrome and the 22q11.2 deletion syndrome. Am. J. Med. Genet., 62, 318.Google Scholar
Lynch, D. R., McDonald-McGinn, D., Zackai, E. H.et al. (1995) Cerebellar atrophy in a patient with velocardiofacial syndrome. J. Med. Genet., 32, 561–3.Google Scholar
Matsouka, R., Takao, A., Kimura, M.et al. (1994) Confirmation that the conotruncal anomaly face syndrome is associated with a deletion within 22q11.2. Am. J. Med. Genet., 53, 285–9.Google Scholar
McDonald-McGinn, D. M., Driscoll, D. A., Bason, L.et al. (1995) Autosomal dominant “Opitz” GBBB syndrome due to a 22q11.2 deletion. Am. J. Med. Genet., 59, 103–13.Google Scholar
McDonald-McGinn, D. M., Emanuel, B. S., Zackai, E. H. (1996) Letter to the Editor: Autosomal dominant “Opitz” GBBB syndrome due to a 22q11.2 deletion. Am. J. Med. Genet., 64, 525–6.Google Scholar
McDonald-McGinn, D. M., Driscoll, D. A., Emanuel, B. S.et al. (1996) The 22q11.2 deletion in African-American patients: an underdiagnosed population. Am. J. Hum. Genet., 59, A20.Google Scholar
McDonald-McGinn, D. M., LaRossa, D., Goldmuntz, E.et al. (1997a) The 22q11.2 deletion: screening, diagnostic workup, and outcome of results; report on 181 patients. Genetic Testing, 1, 99–108.Google Scholar
McDonald-McGinn, D. M., Driscoll, D. A., Emanuel, B. S.et al. (1997b) Detection of a 22q11.2 deletion in cardiac patients suggests a risk for velopharyngeal incompetence. Pediatrics, 99, 1–5.Google Scholar
McDonald-McGinn, D. M., Kirschner, R., Gripp, K. et al. (1999a) Craniosynostosis: another feature of the 22q11.2 deletion syndrome. American Cleft-Palate Craniofacial Association 56th Annual Meeting and Conference Symposium, Scottsdale, AZ.
McDonald-McGinn, D. M., Kirschner, R., Goldmuntz, E.et al. (1999b) The Philadelphia Story: The 22q11.2 Deletion: Report on 250 Patients. Genetic Counseling, 10 (1), 11–24.Google Scholar
McDonald-McGinn, D. M., Tonnesen, M. K., Laufer-Cahana, A.et al. (2001a) Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide fluorescence in situ hybridizationing net!Genet. Med., 3, 23–9.Google Scholar
McDonald-McGinn, D. M., Driscoll, D. A., Tonnesen, M.et al. (2001b) Parent of origin does not determine phenotype in the 22q11.2 deletion. Am. J. Hum. Genet., 69, 285 (A597).Google Scholar
McDonald-McGinn, D. M., Tonnesen, M. K., Saitta, S. et al. (2002a) The Philadelphia Story: Update on our Population of Patients with a 22q11.2 deletion. Deletion 22q11.2 Third International Meeting, Rome, Italy, June 7–8.
McDonald-McGinn, D. M., Driscoll, D. A., Saitta, S.et al. (2002b) Guidelines for prenatal detection of the 22q11.2 deletion. Am. J. Hum. Genet., 71 (4), 198 (A173).Google Scholar
Ming, J. E., McDonald-McGinn, D. M., Megerian, T. E.et al. (1997) Skeletal anomalies in patients with deletions of 22q11. Am. J. Med. Genet., 72, 210–15.Google Scholar
Moss, E. M., Batshaw, M. L., Solot, C. B.et al. (1999) Psychoeducational profile of the 22q11.2 microdeletion: A complex pattern. J. Pediatr., 134, 193–8.Google Scholar
Nickel, R. E. & Magenis, R. E. (1996) Neural tube defects and deletions of 22q11. Am. J. Med. Genet., 66, 25–7.Google Scholar
Prasad, C., Quackenbush, E. J., Whiteman, D.et al. (1997) Limb anomalies in DiGeorge and CHARGE syndromes. Am. J. Med. Genet., 68, 179–81.Google Scholar
Reardon, W., Wilkes, D., Rutland, P.et al. (1997) Craniosynostosis associated with FGFR3 pro250arg mutation results in a range of clinical presentations including unisutural craniosynostosis. J. Med. Genet., 34, 632–6.Google Scholar
Russell, K. L., McDonald-McGinn, D. M., Mahle, W. et al. (2000) Congenital diaphragmatic hernia in the 22q11.2 deletion. Presentation, Second International 22q11.2 Deletion Meeting, June 22–25, Philadelphia, PA.
Ryan, A. K., Goodship, J. A., Wilson, D. I.et al. (1997) Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J. Med. Genet., 34, 798–804.Google Scholar
Sandrin-Garcia, P., Macedo, C., Martelli, L. R.et al. (2002) Recurrent 22q11.2 deletion in a sibship suggestive of parental germline mosaicism in velocardiofacial syndrome. Clin. Genet., 61, 380–3.Google Scholar
Scambler, P. J., Carey, A. H., Wyse, R. K.et al. (1991) Microdeletions within 22q11 associated with sporadic and familial DiGeorge syndrome. Genomics, 10 (1), 201–6.Google Scholar
Schinzel, A. (2001) In Catalogue of Unbalanced Chromosome Aberrations in Man. New York: Walter de Gruyter, Inc., pp. 846–57.
Shaikh, T. H., Kurahashi, H., Saitta, S. C.et al. (2000) Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis. Hum. Mol. Genet., 9, 489–501.Google Scholar
Solot, C., Knightly, C., Handler, S.et al. (2000) Communication disorders in the 22q11.2 microdeletion syndrome. J. Comm. Dis., 33, 187–204.Google Scholar
Solot, C. B., Gerdes, M., Kirschner, R. E.et al. (2001) Communication issues in 22q11.2 deletion syndrome: children at risk. Genet. Med., 3, 67–71.Google Scholar
Sullivan, K. E., McDonald-McGinn, D. M., Driscoll, D. A.et al. (1997) JRA-like polyarthritis in chromosome 22q11.2 deletion syndrome (DiGeorge anomalad/velocardiofacial syndrome/conotruncal anomaly face syndrome). Arthritis Rheumatism, 40, 430–6.Google Scholar
Sullivan, K. E., Jawad, A. F., Randall, P.et al. (1998) The frequency and severity of immunodeficiency in chromosome 22q11.2 deletion syndromes (DiGeorge syndrome/Velocardiofacial syndrome). Clin. Immunol. Immunopathol., 86, 141–6.Google Scholar
Sullivan, K. E., McDonald-McGinn, D., Driscoll, D. A.et al. (1999) Longitudinal analysis of lymphocyte function and numbers in the first year of life in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/Velocardiofacial syndrome). Clin. Diagn. Lab. Immunol., 6, 906–11.Google Scholar
Thompson, J. S. & Thompson, M. W. (1986) Genetics in Medicine, 4th Edn. Philadelphia, PA: W. B. Saunders Company.
Tonnesen, M., McDonald-McGinn, D. M., Valverde, K.et al. (2001) Affected parents with a 22q11.2 deletion: the need for basic and ongoing educational health, and supportive counseling. Am. J. Hum. Genet., 69 (4), 223 (A241).Google Scholar
Wang, P., Solot, C., Gerdes, M.et al. (1998) Developmental presentation of 22q11.2 deletion. Dev. Behav. Pediatr., 19, 342–5.Google Scholar
Weinzimer, S. A., McDonald-McGinn, D. M., Driscoll, D. A.et al. (1998) Growth hormone deficiency in patients with a 22q11.2 deletion: expanding the phenotype. Pediatrics, 101, 929–32.Google Scholar
Wilson, D. I., Cross, I. E., Goodship, J. A.et al. (1992) A prospective cytogenetic study of 36 cases of DiGeorge syndrome. Am. J. Hum. Genet., 51, 957–63.Google Scholar
Wu, H-Y., Rusnack, S. L., Bellah, R. D.et al. (2002) Genitourinary malformations in chromosome 22q11.2 deletion. J. Urology, 168, 2564–5.Google Scholar

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