title: Intergenerational and intrafamilial phenotypic variability in 22q11.2 deletion syndrome subjects.
abstract: BACKGROUND
  22q11.2 deletion syndrome (22q11.2DS) is a common microdeletion syndrome, which occurs in approximately 1:4000 births. Familial autosomal dominant recurrence of the syndrome is detected in about 8-28% of the cases. Aim of this study is to evaluate the intergenerational and intrafamilial phenotypic variability in a cohort of familial cases carrying a 22q11.2 deletion.
  
  
  METHODS
  Thirty-two 22q11.2DS subjects among 26 families were enrolled.
  
  
  RESULTS
  Second generation subjects showed a significantly higher number of features than their transmitting parents (212 vs 129, P = 0.0015). Congenital heart defect, calcium-phosphorus metabolism abnormalities, developmental and speech delay were more represented in the second generation (P < 0.05). Ocular disorders were more frequent in the parent group. No significant difference was observed for the other clinical variables. Intrafamilial phenotypic heterogeneity was identified in the pedigrees. In 23/32 families, a higher number of features were found in individuals from the second generation and a more severe phenotype was observed in almost all of them, indicating the worsening of the phenotype over generations. Both genetic and epigenetic mechanisms may be involved in the phenotypic variability.
  
  
  CONCLUSIONS
  Second generation subjects showed a more complex phenotype in comparison to those from the first generation. Both ascertainment bias related to patient selection or to the low rate of reproductive fitness of adults with a more severe phenotype, and several not well defined molecular mechanism, could explain intergenerational and intrafamilial phenotypic variability in this syndrome.
authors.forename: Emilia
authors.initials: E
authors.lastname: Cirillo
authors.forename: Giuliana
authors.initials: G
authors.lastname: Giardino
authors.forename: Vera
authors.initials: V
authors.lastname: Gallo
authors.forename: Pamela
authors.initials: P
authors.lastname: Puliafito
authors.forename: Chiara
authors.initials: C
authors.lastname: Azzari
authors.forename: Rosa
authors.initials: R
authors.lastname: Bacchetta
authors.forename: Fabio
authors.initials: F
authors.lastname: Cardinale
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cicalese
authors.forename: Rita
authors.initials: R
authors.lastname: Consolini
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: Baldassarre
authors.initials: B
authors.lastname: Martire
authors.forename: Cristina
authors.initials: C
authors.lastname: Molinatto
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Scarano
authors.forename: Annarosa
authors.initials: A
authors.lastname: Soresina
authors.forename: Caterina
authors.initials: C
authors.lastname: Cancrini
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Digilio
authors.affiliation: Department of Translational Medicine, "Federico II" University, Naples, Italy. pignata@unina.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Pignata
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D015331:Cohort Studies; D004062:DiGeorge Syndrome / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype