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01-07-2013 | Original Article

Defining new guidelines for screening the 22q11.2 deletion based on a clinical and dysmorphologic evaluation of 194 individuals and review of the literature

Authors: Fabíola P. Monteiro, Társis P. Vieira, Ilária C. Sgardioli, Miriam C. Molck, Ana Paula Damiano, Josiane Souza, Isabella L. Monlleó, Marshall I. B. Fontes, Agnes C. Fett-Conte, Têmis M. Félix, Gabriela F. Leal, Erlane M.Ribeiro, Claudio E. M. Banzato, Clarissa de R. Dantas, Iscia Lopes-Cendes, Vera Lúcia Gil-da-Silva-Lopes

Published in: European Journal of Pediatrics | Issue 7/2013

Abstract

The 22q11.2 deletion is the most frequent interstitial deletion in humans and presents a wide phenotypic spectrum, with over 180 clinical manifestations described. Distinct studies have detected frequencies of the deletion ranging from 0 % to 75 %, depending on the studied population and selection criteria adopted. Due to the lack of consensus in this matter, several studies have been conducted aiming to define which patients would be eligible for screening; however, the issue is still up for debate. In order to contribute to the delineation of possible clinical and dysmorphologic guidelines to optimize decision making in the clinical setting, 194 individuals with variable features of the 22q11.2 deletion syndromes (22q11.2DS) were evaluated. Group I, clinical suspicion of 22q11.2DS with palatal anomalies; Group II, clinical suspicion without palatal anomalies; Group III, cardiac malformations associated with the 22q11.2DS; and Group IV, juvenile-onset schizophrenia. Multiplex ligation-dependent probe amplification was used for screening the 22q11.2 deletion, which was detected in 45 patients (23.2 %), distributed as such: Group I, 35/101 (34.7 %); Group II, 4/18 (22.2 %); Group III, 6/52 (11.5 %); and Group IV, 0/23 (0 %). Clinical data were analyzed by frequency distribution and statistically. Based on the present results and on the review of the literature, we propose a set of guidelines for screening patients with distinct manifestations of the 22q11.2DS in order to maximize resources. In addition, we report the dysmorphic features which we found to be statistically correlated with the presence of the 22q11.2DS.

Adachi M, Tachibana K, Masuno M, Makita Y, Maesaka H, Okada T, Hizukuri K, Imaizumi K, Kuroki Y, Kurahashi H, Suwa S (1998) Clinical characteristics of children with hypoparathyroidism due to 22q11.2 microdeletion. Eur J Pediatr 157(1):34–38PubMedCrossRef

Agergaard P, Hebert A, Sørensen KM, Ostergaard JR, Olesen C (2011) Can clinical assessment detect 22q11.2 deletions in patients with cardiac malformations? A review. Eur J Med Genet 54(1):3–8PubMedCrossRef

Amati F, Conti E, Novelli A, Bengala M, Diglio MC, Marino B, Giannotti A, Gabrielli O, Novelli G, Dallapiccola B (1999) Atypical deletions suggest five 22q11.2 critical regions related to the DiGeorge/velo-cardio-facial syndrome. Eur J Hum Genet 7(8):903–909PubMedCrossRef

Amati F, Mari A, Digilio MC, Mingarelli R, Marino B, Giannotti A, Novelli G, Dallapiccola B (1995) 22q11 deletions in isolated and syndromic patients with Tetralogy of Fallot. Hum Genet 95(5):479–482PubMedCrossRef

Arinami T, Ohtsuki T, Takase K, Shimizu H, Yoshikawa T, Horigome H, Nakayama J, Toru M (2001) Screening for 22q11 deletions in a schizophrenia population. Schizophr Res 52(3):167–170PubMedCrossRef

Bartsch O, Nemecková M, Kocárek E, Wagner A, Puchmajerová A, Poppe M, Ounap K, Goetz P (2003) DiGeorge/velocardiofacial syndrome: FISH studies of chromosomes 22q11 and 10p14, and clinical reports on the proximal 22q11 deletion. Am J Med Genet A 117A(1):1–5PubMedCrossRef

Bashir MA, Hodgkinson PD, Montgomery T, Splitt M (2008) 22q11 Deletion in children with cleft lip and palate—is routine screening justified? J Plast Reconstr Aesthet Surg 61(2):130–132PubMedCrossRef

Bassett AS, Chow EW (2008) Schizophrenia and 22q11.2 deletion syndrome. Curr Psychiatry Rep 10(2):148–157PubMedCrossRef

Bassett AS, Hodgkinson K, Chow EW, Correia S, Scutt LE, Weksberg R (1998) 22q11 deletion syndrome in adults with schizophrenia. Am J Med Genet 81(4):328–337PubMedCrossRef

10.

Baumer A, Dutly F, Balmer D, Riegel M, Tükel T, Krajewska-Walasek M, Schinzel AA (1998) High level of unequal meiotic crossovers at the origin of the 22q11. 2 and 7q11.23 deletions. Hum Mol Genet 7(5):887–894PubMedCrossRef

11.

Beauchesne LM, Warnes CA, Connolly HM, Ammash NM, Grogan M, Jalal SM, Michels VV (2005) Prevalence and clinical manifestations of 22q11.2 microdeletion in adults with selected conotruncal anomalies. J Am Coll Cardiol 45(4):595–598PubMedCrossRef

12.

Boorman JG, Varma S, Ogilvie CM (2001) Velopharyngeal incompetence and chromosome 22q11 deletion. Lancet 357(9258):774PubMedCrossRef

13.

Borgmann S, Luhmer I, Arslan-Kirchner M, Kallfelz HC, Schmidtke J (1999) A search for chromosome 22q11.2 deletions in a series of 176 consecutively catheterized patients with congenital heart disease: no evidence for deletions in non-syndromic patients. Eur J Pediatr 158(12):958–963PubMedCrossRef

14.

Botto LD et al (2003) A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics 112(1 Pt 1):101–107PubMedCrossRef

15.

Brunet A, Gabau E, Perich RM, Valdesoiro L, Brun C, Caballín MR, Guitart M (2006) Microdeletion and microduplication 22q11.2 screening in 295 patients with clinical features of DiGeorge/velocardiofacial syndrome. Am J Med Genet A 140(22):2426–2432PubMed

16.

Carlson C, Sirotkin H, Pandita R, Goldberg R, McKie J, Wadey R, Patanjali SR, Weissman SM, Anyane-Yeboa K, Warburton D, Scambler P, Shprintzen R, Kucherlapati R, Morrow BE (1997) Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients. Am J Hum Genet 61(3):620–629PubMedCrossRef

17.

Carotti A, Digilio MC, Piacentini G, Saffirio C, Di Donato RM, Marino B (2008) Cardiac defects and results of cardiac surgery in 22q11.2 deletion syndrome. Dev Disabil Res Rev 14(1):35–42PubMedCrossRef

18.

Cayler GG (1969) Cardiofacial syndrome. Congenital heart disease and facial weakness, a hitherto unrecognized association. Arch Dis Child 44:69–75PubMedCrossRef

19.

Chessa M, Butera G, Bonhoeffer P, Iserin L, Kachaner J, Lyonnet S, Munnich A, Sidi D, Bonnet D (1998) Relation of genotype 22q11 deletion to phenotype of pulmonary vessels in Tetralogy of Fallot and pulmonary atresia-ventricular septal defect. Heart 79(2):186–190PubMed

20.

Cuneo BF (2001) 22q11.2 deletion syndrome: DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes. Curr Opin Pediatr 13(5):465–472PubMedCrossRef

21.

Derbent M, Yilmaz Z, Baltaci V, Saygili A, Varan B, Tokel K (2003) Chromosome 22q11.2 deletion and phenotypic features in 30 patients with conotruncal heart defects. Am J Med Genet A 116A(2):129–135PubMedCrossRef

22.

DiGeorge AM (1968) Congenital absence of the thymus and its immunologic consequences: concurrence with congenital hypoparathyroidism. Birth Defects Orig Ser Art IV(1):116–121

23.

Drew LJ, Crabtree GW, Markx S, Stark KL, Chaverneff F, Xu B, Mukai J, Fenelon K, Hsu PK, Gogos JA, Karayiorgou M (2011) The 22q11.2 microdeletion: fifteen years of insights into the genetic and neural complexity of psychiatric disorders. Int J Dev Neurosci 29(3):259–281PubMedCrossRef

24.

Driscoll DA, Salvin J, Sellinger B, Budarf ML, McDonald-McGinn DM, Zackai EH, Emanuel BS (1993) Prevalence of 22q11 microdeletions in DiGeorge and velocardiofacial syndromes: implications for genetic counselling and prenatal diagnosis. J Med Genet 30(10):813–817PubMedCrossRef

25.

Edelmann L, Pandita RK, Spiteri E, Funke B, Goldberg R, Palanisamy N, Chaganti RS, Magenis E, Shprintzen RJ, Morrow BE (1999) A common molecular basis for rearrangement disorders on chromosome 22q11. Hum Mol Genet 8(7):1157–1167PubMedCrossRef

26.

Fernandez L, Lapunzina P, Arjona D, Lopez Pajares I, Garcia-Guereta L, Elorza D, Burgueros M, De Torres ML, Mori MA, Palomares M, Garcia-Alix A, Delicado A (2005) Comparative study of three diagnostic approaches (FISH, STRs and MLPA) in 30 patients with 22q11.2 deletion syndrome. Clin Genet 68:373–378PubMedCrossRef

27.

Fokstuen S, Arbenz U, Artan S, Dutly F, Bauersfeld U, Brecevic L, Fasnacht M, Röthlisberger B, Schinzel A (1998) 22q11.2 deletions in a series of patients with non-selective congenital heart defects: incidence, type of defects and parental origin. Clin Genet 53(1):63–69PubMedCrossRef

28.

Giannotti A, Digilio MC, Marino B, Mingarelli R, Dallapiccola B (1994) Cayler cardiofacial syndrome and del 22q11: part of the CATCH22 phenotype. Am J Med Genet 53:303–304PubMedCrossRef

29.

Gioli-Pereira L, Pereira AC, Bergara D, Mesquita S, Lopes AA, Krieger JE (2008) Frequency of 22q11.2 microdeletion in sporadic non-syndromic Tetralogy of Fallot cases. Int J Cardiol 126(3):374–378PubMedCrossRef

30.

Goldmuntz E, Clark BJ, Mitchell LE, Jawad AF, Cuneo BF, Reed L, McDonald-McGinn D, Chien P, Feuer J, Zackai EH, Emanuel BS, Driscoll DA (1998) Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol 32(2):492–498PubMedCrossRef

31.

Goodship J, Cross I, LiLing J, Wren C (1998) A population study of chromosome 22q11 deletions in infancy. Arch Dis Child 79(4):348–351PubMedCrossRef

32.

Gothelf D, Frisch A, Munitz H, Rockah R, Aviram A, Mozes T, Birger M, Weizman A, Frydman M (1997) Velocardiofacial manifestations and microdeletions in schizophrenic inpatients. Am J Med Genet 72(4):455–461PubMedCrossRef

33.

Halder A, Jain M, Chaudhary I, Kabra M (2010) Prevalence of 22q11.2 microdeletion in 146 patients with cardiac malformation in a referral hospital of North India. BMC Med Genet 11:101PubMedCrossRef

34.

Hay BN (2007) Deletion 22q11: spectrum of associated disorders. Semin Pediatr Neurol 14(3):136–139PubMedCrossRef

35.

Hofbeck M, Rauch A, Buheitel G, Leipold G, von der Emde J, Pfeiffer R, Singer H (1998) Monosomy 22q11 in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. Heart 79(2):180–185PubMed

36.

Horowitz A, Shifman S, Rivlin N, Pisanté A, Darvasi A (2005) A survey of the 22q11 microdeletion in a large cohort of schizophrenia patients. Schizophr Res 73(2–3):263–267PubMedCrossRef

37.

Insel TR (2010) Rethinking schizophrenia. Nature 468(7321):187–193PubMedCrossRef

38.

Iserin L, de Lonlay P, Viot G, Sidi D, Kachaner J, Munnich A, Lyonnet S, Vekemans M, Bonnet D (1998) Prevalence of the microdeletion 22q11 in newborn infants with congenital conotruncal cardiac anomalies. Eur J Pediatr 157(11):881–884PubMedCrossRef

39.

Jalali GR, Vorstman JA, Errami A, Vijzelaar R, Biegel J, Shaikh T, Emanuel BS (2008) Detailed analysis of 22q11.2 with a high density MLPA probe set. Hum Mutat 29(3):433–440PubMedCrossRef

40.

Karayiorgou M, Gogos JA (2004) The molecular genetics of the 22q11-associated schizophrenia. Brain Res Mol Brain Res 132(2):95–104PubMedCrossRef

41.

Karayiorgou M, Morris MA, Morrow B, Shprintzen RJ, Goldberg R, Borrow J, Gos A, Nestadt G, Wolyniec PS, Lasseter VK et al (1995) Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proc Natl Acad Sci U S A 92(17):7612–7616PubMedCrossRef

42.

Khositseth A, Tocharoentanaphol C, Khowsathit P, Ruangdaraganon N (2005) Chromosome 22q11 deletions in patients with conotruncal heart defects. Pediatr Cardiol 26(5):570–573PubMedCrossRef

43.

Kitsiou-Tzeli S et al (2004) Detection of 22q11.2 deletion among 139 patients with Di George/velocardiofacial syndrome features. In Vivo 18(5):603–608PubMed

44.

Kobrynski LJ, Sullivan KE (2007) Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 370:1443–1452PubMedCrossRef

45.

Maeda J, Yamagishi H, Matsuoka R, Ishihara J, Tokumura M, Fukushima H, Ueda H, Takahashi E, Yoshiba S, Kojima Y (2000) Frequent association of 22q11.2 deletion with Tetralogy of Fallot. Am J Med Genet 92(4):269–272PubMedCrossRef

46.

Matsuoka R, Takao A, Kimura M, Imamura S, Kondo C, Joh-o K, Ikeda K, Nishibatake M, Ando M, Momma K (1994) Confirmation that the conotruncal anomaly face syndrome is associated with a deletion within 22q11.2. Am J Med Genet 53:285–289PubMedCrossRef

47.

McDonald-McGinn DM, Driscoll DA, Bason L, Christensen K, Lynch D, Sullivan K, Canning D, Zavod W, Quinn N, Rome J (1995) Autosomal dominant “Opitz” GBBB syndrome due to a 22q11.2 deletion. Am J Med Genet 59(1):103–113PubMedCrossRef

48.

McDonald-McGinn DM, Kirschner R, Goldmuntz E, Sullivan K, Eicher P, Gerdes M, Moss E, Solot C, Wang P, Jacobs I, Handler S, Knightly C, Heher K, Wilson M, Ming JE, Grace K, Driscoll D, Pasquariello P, Randall P, Larossa D, Emanuel BS, Zackai EH (1999) The Philadelphia story: the 22q11.2 deletion: report on 250 patients. Genet Couns 10:11–24PubMed

49.

McDonald-McGinn DM, LaRossa D, Goldmuntz E, Sullivan K, Eicher P, Gerdes M, Moss E, Wang P, Solot C, Schultz P, Lynch D, Bingham P, Keenan G, Weinzimer S, Ming JE, Driscoll D, Clark BJ 3rd, Markowitz R, Cohen A, Moshang T, Pasquariello P, Randall P, Emanuel BS, Zackai EH (1997) The 22q11.2 deletion: screening, diagnostic workup, and outcome of results; report on 181 patients. Genet Test 1(2):99–108PubMedCrossRef

50.

McDonald-McGinn DM, Tonnesen MK, Laufer-Cahana A, Finucane B, Driscoll DA, Emanuel BS, Zackai EH (2001) Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net! Genet Med 3:23–29PubMedCrossRef

51.

McElhinney DB, Driscoll DA, Levin ER, Jawad AF, Emanuel BS, Goldmuntz E (2003) Chromosome 22q11 deletion in patients with ventricular septal defect: frequency and associated cardiovascular anomalies. Pediatrics 112(6 Pt 1):e472PubMedCrossRef

52.

McQuade L, Christodoulou J, Budarf M, Sachdev R, Wilson M, Emanuel B, Colley A (1999) Patient with a 22q11.2 deletion with no overlap of the minimal DiGeorge syndrome critical region (MDGCR). Am J Med Genet 86(1):27–33PubMedCrossRef

53.

Mingarelli R et al (1996) The search for hemizygosity at 22qll in patients with isolated cleft palate. J Craniofac Genet Dev Biol 16(2):118–121PubMed

54.

Momma K (2010) Cardiovascular anomalies associated with chromosome 22q11.2 deletion syndrome. Am J Cardiol 105(11):1617–1624PubMedCrossRef

55.

Momma K, Kondo C, Matsuoka R (1996) Tetralogy of Fallot with pulmonary atresia associated with chromosome 22q11 deletion. J Am Coll Cardiol 27(1):198–202PubMedCrossRef

56.

Momma K, Matsuoka R, Takao A (1999) Aortic arch anomalies associated with chromosome 22q11 deletion (CATCH 22). Pediatr Cardiol 20(2):97–102PubMedCrossRef

57.

Oh AK, Workman LA, Wong GB (2007) Clinical correlation of chromosome 22q11.2 fluorescent in situ hybridization analysis and velocardiofacial syndrome. Cleft Palate Craniofac J 44(1):62–66PubMedCrossRef

58.

Oskarsdóttir S, Persson C, Eriksson BO, Fasth A (2005) Presenting phenotype in 100 children with the 22q11 deletion syndrome. Eur J Pediatr 164(3):146–153PubMedCrossRef

59.

Ou Z, Berg JS, Yonath H, Enciso VB, Miller DT, Picker J, Lenzi T, Keegan CE, Sutton VR, Belmont J, Chinault AC, Lupski JR, Cheung SW, Roeder E, Patel A (2008) Microduplications of 22q11.2 are frequently inherited and are associated with variable phenotypes. Genet Med 10(4):267–277PubMedCrossRef

60.

Perez E, Sullivan KE (2002) Chromosome 22q11.2 deletion syndrome (DiGeorge and velocardiofacial syndromes). Curr Opin Pediatr 14(6):678–683PubMedCrossRef

61.

Portnoï MF (2009) Microduplication 22q11.2: a new chromosomal syndrome. Eur J Med Genet 52(2–3):88–93PubMedCrossRef

62.

Reish O, Finkelstein Y, Mesterman R, Nachmani A, Wolach B, Fejgin M, Amiel A (2003) Is isolated palatal anomaly an indication to screen for 22q11 region deletion? Cleft Palate Craniofac J 40(2):176–179PubMedCrossRef

63.

Ruiter EM, Bongers EM, Smeets DF, Kuijpers-Jagtman AM, Hamel BC (2003) No justification of routine screening for 22q11 deletions in patients with overt cleft palate. Clin Genet 64(3):216–219PubMedCrossRef

64.

Ryan AK, Goodship JA, Wilson DI, Philip N, Levy A, Seidel H, Schuffenhauer S, Oechsler H, Belohradsky B, Prieur M, Aurias A, Raymond FL, Clayton-Smith J, Hatchwell E, McKeown C, Beemer FA, Dallapiccola B, Novelli G, Hurst JA, Ignatius J, Green AJ, Winter RM, Brueton L, Brøndum-Nielsen K, Scambler PJ et al (1997) Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet 34(10):798–804PubMedCrossRef

65.

Sandrin-Garcia P, Abramides DV, Martelli LR, Ramos ES, Richieri-Costa A, Passos GA (2007) Typical phenotypic spectrum of velocardiofacial syndrome occurs independently of deletion size in chromosome 22q11.2. Mol Cell Biochem 303(1–2):9–17PubMedCrossRef

66.

Sandrin-Garcia P, Richieri-Costa A, Tajara EH, Carvalho-Salles AB, Fett-Conte AC (2007) Fluorescence in situ hybridization (FISH) screening for the 22q11.2 deletion in patients with clinical features of velocardiofacial syndrome but without cardiac anomalies. Genet Mol Biol 30(1):21–24CrossRef

67.

Scambler PJ, Carey AH, Wyse RK, Roach S, Dumanski JP, Nordenskjold M, Williamson R (1991) Microdeletions within 22q11 associated with sporadic and familial DiGeorge syndrome. Genomics 10(1):201–206PubMedCrossRef

68.

Shprintzen RJ, Goldberg RB, Lewin ML, Sidoti EJ, Berkman MD, Argamaso RV, Young D (1978) A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate Craniofac J 15:56–62

69.

Shprintzen RJ, Higgins AM, Antshel K, Fremont W, Roizen N, Kates W (2005) Velo-cardio-facial syndrome. Curr Opin Pediatr 17(6):725–730PubMedCrossRef

70.

Simioni M, Vieira TP, Sgardioli IC, Freitas EL, Rosenberg C, Maurer-Morelli CV, Lopes-Cendes I, Fett-Conte AC, Gil-da-Silva-Lopes VL (2012) Insertional translocation of 15q25-q26 into 11p13 and duplication at 8p23.1characterized by high resolution arrays in a boy with congenital malformations and aniridia. Am J Med Genet A 158(11):2905–2910

71.

Sivertsen A, Lie RT, Wilcox AJ, Abyholm F, Vindenes H, Haukanes BI, Houge G (2007) Prevalence of duplications and deletions of the 22q11 DiGeorge syndrome region in a population-based sample of infants with cleft palate. Am J Med Genet A 143(2):129–134PubMed

72.

Sporn A, Addington A, Reiss AL et al (2004) 22q11 deletion syndrome in childhood onset schizophrenia: an update. Mol Psychiatry 9:225–226PubMedCrossRef

73.

Sugama S, Namihira T, Matsuoka R, Taira N, Eto Y, Maekawa K (1999) Psychiatric inpatients and chromosome deletions within 22q11.2. J Neurol Neurosurg Psychiatry 67(6):803–806PubMedCrossRef

74.

Swillen A, Devriendt K, Legius E, Eyskens B, Dumoulin M, Gewillig M, Fryns JP (1997) Intelligence and psychosocial adjustment in velocardiofacial syndrome: a study of 37 children and adolescents with VCFS. J Med Genet 34(6):453–458PubMedCrossRef

75.

Swillen A, Vogels A, Devriendt K, Fryns JP (2000) Chromosome 22q11 deletion syndrome: update and review of the clinical features, cognitive-behavioral spectrum, and psychiatric complications. Am J Med Genet 97(2):128–135PubMedCrossRef

76.

Takahashi K, Kido S, Hoshino K, Ogawa K, Ohashi H, Fukushima Y (1995) Frequency of a 22q11 deletion in patients with conotruncal cardiac malformations: a prospective study. Eur J Pediatr 154(11):878–881PubMedCrossRef

77.

Taylor SC, Morris G, Wilson D, Davies SJ, Gregory JW (2003) Hypoparathyroidism and 22q11 deletion syndrome. Arch Dis Child 88(6):520–522PubMedCrossRef

78.

Tobias ES, Morrison N, Whiteford ML, Tolmie JL (1999) Towards earlier diagnosis of 22q11 deletions. Arch Dis Child 81(6):513–514PubMedCrossRef

79.

Usiskin SI et al (1999) Velocardiofacial syndrome in childhood-onset schizophrenia. J Am Acad Child Adolesc Psychiatry 38(12):1536–1543PubMedCrossRef

80.

Wiehahn GJ, Bosch GP, du Preez RR, Pretorius HW, Karayiorgou M, Roos JL (2004) Assessment of the frequency of the 22q11 deletion in Afrikaner schizophrenic patients. Am J Med Genet B Neuropsychiatr Genet 129B(1):20–22PubMedCrossRef

81.

Yong DE, Booth P, Baruni J, Massie D, Stephen G, Couzin D, Dean JC (1999) Chromosome 22q11 microdeletion and congenital heart disease—a survey in a paediatric population. Eur J Pediatr 158(7):566–570PubMedCrossRef

Title: Defining new guidelines for screening the 22q11.2 deletion based on a clinical and dysmorphologic evaluation of 194 individuals and review of the literature
Authors: Fabíola P. Monteiro
Társis P. Vieira
Ilária C. Sgardioli
Miriam C. Molck
Ana Paula Damiano
Josiane Souza
Isabella L. Monlleó
Marshall I. B. Fontes
Agnes C. Fett-Conte
Têmis M. Félix
Gabriela F. Leal
Erlane M.Ribeiro
Claudio E. M. Banzato
Clarissa de R. Dantas
Iscia Lopes-Cendes
Vera Lúcia Gil-da-Silva-Lopes
Publication date: 01-07-2013
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Pediatrics / Issue 7/2013
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI: https://doi.org/10.1007/s00431-013-1964-0

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Defining new guidelines for screening the 22q11.2 deletion based on a clinical and dysmorphologic evaluation of 194 individuals and review of the literature

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