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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2014

Open Access 01-12-2014 | Research article

Intergenerational and intrafamilial phenotypic variability in 22q11.2 Deletion syndrome subjects

Authors: Emilia Cirillo, Giuliana Giardino, Vera Gallo, Pamela Puliafito, Chiara Azzari, Rosa Bacchetta, Fabio Cardinale, Maria Pia Cicalese, Rita Consolini, Silvana Martino, Baldassarre Martire, Cristina Molinatto, Alessandro Plebani, Gioacchino Scarano, Annarosa Soresina, Caterina Cancrini, Paolo Rossi, Maria Cristina Digilio, Claudio Pignata

Published in: BMC Medical Genetics | Issue 1/2014

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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.
Appendix
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Metadata
Title
Intergenerational and intrafamilial phenotypic variability in 22q11.2 Deletion syndrome subjects
Authors
Emilia Cirillo
Giuliana Giardino
Vera Gallo
Pamela Puliafito
Chiara Azzari
Rosa Bacchetta
Fabio Cardinale
Maria Pia Cicalese
Rita Consolini
Silvana Martino
Baldassarre Martire
Cristina Molinatto
Alessandro Plebani
Gioacchino Scarano
Annarosa Soresina
Caterina Cancrini
Paolo Rossi
Maria Cristina Digilio
Claudio Pignata
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2014
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-15-1

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