Clinical features of chromosome 22q11.2 microdeletion syndrome in 208 Chilean patients

Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin‐American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines.

[1]  C. Gillberg,et al.  Autism, ADHD, mental retardation and behavior problems in 100 individuals with 22q11 deletion syndrome. , 2009, Research in developmental disabilities.

[2]  K. Sullivan,et al.  Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes , 2007, The Lancet.

[3]  B De Smedt,et al.  Intellectual abilities in a large sample of children with Velo-Cardio-Facial Syndrome: an update. , 2007, Journal of intellectual disability research : JIDR.

[4]  E. Zackai,et al.  The 22q11.2 deletion in African‐American patients: An underdiagnosed population? , 2005, American journal of medical genetics. Part A.

[5]  C. Persson,et al.  Presenting phenotype in 100 children with the 22q11 deletion syndrome , 2005, European Journal of Pediatrics.

[6]  Joe C. Adams,et al.  Full spectrum of malformations in velo-cardio-facial syndrome/DiGeorge syndrome mouse models by altering Tbx1 dosage. , 2004, Human molecular genetics.

[7]  A. Fasth,et al.  Incidence and prevalence of the 22q11 deletion syndrome: a population-based study in Western Sweden , 2004, Archives of Disease in Childhood.

[8]  Lorenzo D Botto,et al.  A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. , 2003, Pediatrics.

[9]  H. Cox,et al.  22q11 deletion: a multisystem disorder requiring multidisciplinary input , 2003, Archives of disease in childhood.

[10]  F. Vitelli,et al.  A genetic link between Tbx1 and fibroblast growth factor signaling. , 2002, Development.

[11]  B. Cuneo.  22q11.2 deletion syndrome: DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes , 2001, Current opinion in pediatrics.

[12]  M. Morishima,et al.  Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge/del22q11 syndromes , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[13]  R. CeciliaMéndez,et al.  Clinical heterogeneity of the chromosome 22q11 microdeletion syndrome , 2001 .

[14]  V. Papaioannou,et al.  DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1 , 2001, Nature Genetics.

[15]  P. Scambler,et al.  Tbx1 haploinsufficiency in the DiGeorge syndrome region causes aortic arch defects in mice , 2001, Nature.

[16]  Birgit Funke,et al.  TBX1 Is Responsible for Cardiovascular Defects in Velo-Cardio-Facial/DiGeorge Syndrome , 2001, Cell.

[17]  B. Pongpanich,et al.  Chromosome 22q11 deletion syndrome: the first three cases reported in Thailand. , 1999, Journal of the Medical Association of Thailand = Chotmaihet thangphaet.

[18]  I. Cross,et al.  A population study of chromosome 22q11 deletions in infancy , 1998, Archives of disease in childhood.

[19]  K. Devriendt,et al.  The annual incidence of DiGeorge/velocardiofacial syndrome. , 1998, Journal of medical genetics.

[20]  B. Morrow,et al.  Molecular and clinical study of 183 patients with conotruncal anomaly face syndrome , 1998, Human Genetics.

[21]  A. Green,et al.  Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. , 1997, Journal of medical genetics.

[22]  T. Takato,et al.  Craniofacial morphology of conotruncal anomaly face syndrome. , 1997, The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association.

[23]  E. Zackai,et al.  Detection of a 22q11.2 deletion in cardiac patients suggests a risk for velopharyngeal incompetence. , 1997, Pediatrics.

[24]  I. Dunham,et al.  Molecular definition of the 22q11 deletions in velo-cardio-facial syndrome. , 1995, American journal of human genetics.

[25]  A. Schinzel,et al.  The Fate of Children with Microdeletion 22q11.2 Syndrome and Congenital Heart Defect: Clinical Course and Cardiac Outcome , 2007, Pediatric Cardiology.

[26]  G. Repetto,et al.  [Clinical findings and immunologic variability in 9 patients with DiGeorge syndrome]. , 2004, Revista médica de Chile (Impresa).

[27]  I. MarleneAglony,et al.  Clinical findings and immunologic variability in 9 patients with DiGeorge syndrome , 2004 .

[28]  Ingeborg Stalmans,et al.  VEGF: A modifier of the del22q11 (DiGeorge) syndrome? , 2003, Nature Medicine.

[29]  E. Zackai,et al.  Neuropsychological profile of children and adolescents with the 22q11.2 microdeletion , 2001, Genetics in Medicine.

[30]  G. Repetto,et al.  [Clinical heterogeneity of the chromosome 22q11 microdeletion syndrome]. , 2001, Revista médica de Chile (Impresa).

[31]  E. Zackai,et al.  Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: Cast a wide FISHing net! , 2001, Genetics in Medicine.

[32]  E. Zackai,et al.  The Philadelphia story: the 22q11.2 deletion: report on 250 patients. , 1999, Genetic counseling.

[33]  K. Devriendt,et al.  Presenting symptoms and clinical features in 130 patients with the velo-cardio-facial syndrome. The Leuven experience. , 1999, Genetic counseling.

[34]  I. Naert,et al.  The Leuven experience , 1997 .