title: Prenatal diagnosis of 24 cases of microduplication 22q11.2: an investigation of phenotype-genotype correlations.
abstract: OBJECTIVE
  Microduplication 22q11.2 is primarily characterized by a highly variable clinical phenotype, which ranges from apparently normal or slightly dysmorphic features (in the presence or absence of learning disorders) to severe malformations with profound mental retardation. Hence, genetic counseling is particularly challenging when microduplication 22q11.2 is identified in a prenatal diagnosis. Here, we report on 24 prenatal cases of microduplication 22q11.2.
  
  
  METHODS
  Seventeen of the cases were also reanalyzed by microarray analysis, in order to determine copy number variations (CNVs, which are thought to influence expressivity). We also searched for possible correlations between fetal phenotypes, indications for invasive prenatal diagnosis, inheritance, and pregnancy outcomes.
  
  
  RESULTS
  Of the 24 cases, 15 were inherited, six occurred de novo, and three were of unknown origin. Termination of pregnancy occurred in seven cases and was mainly decided on the basis of ultrasound findings. Moreover, additional CNVs were found in some patients and we try to make a genotype-phenotype correlation.
  
  
  CONCLUSIONS
  We discuss the complexity of genetic counseling for microduplication 22q11.2 and comment on possible explanations for the clinical heterogeneity of this syndrome. In particular, we assessed the co-existence of additional CNVs and their contribution to phenotypic variations in chromosome 22q11.2 microduplication syndrome.
authors.affiliation: Unité de Cytogénétique, Département de Génétique, Hôpital Robert Debré-AP-HP, CHU Paris, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Dupont
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Grati
authors.forename: Kwong Wai
authors.initials: KW
authors.lastname: Choy
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jaillard
authors.forename: Jérôme
authors.initials: J
authors.lastname: Toutain
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Maurin
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Martínez-Conejero
authors.forename: Claire
authors.initials: C
authors.lastname: Beneteau
authors.forename: Aurélie
authors.initials: A
authors.lastname: Coussement
authors.forename: Denise
authors.initials: D
authors.lastname: Molina-Gomes
authors.forename: Nina
authors.initials: N
authors.lastname: Horelli-Kuitunen
authors.forename: Azzedine
authors.initials: A
authors.lastname: Aboura
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Tabet
authors.forename: Justine
authors.initials: J
authors.lastname: Besseau-Ayasse
authors.forename: Bettina
authors.initials: B
authors.lastname: Bessieres-Grattagliano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Simoni
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ayala
authors.forename: Brigitte
authors.initials: B
authors.lastname: Benzacken
authors.forename: François
authors.initials: F
authors.lastname: Vialard
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D058674:Chromosome Duplication / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis; D004062:DiGeorge Syndrome / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology; D011296:Prenatal Diagnosis / Q000379:methods*