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

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Article number1
JournalBMC Medical Genetics
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 2 2014

Fingerprint

DiGeorge Syndrome
Phenotype
Genetic Fitness
Language Development Disorders
Congenital Heart Defects
Pedigree
Epigenomics
Phosphorus
Patient Selection
Parturition
Calcium
Recurrence

Keywords

  • 22q11.2 deletion syndrome
  • DiGeorge syndrome
  • Immunodeficiency
  • Phenotypic variability

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Cirillo, E., Giardino, G., Gallo, V., Puliafito, P., Azzari, C., Bacchetta, R., ... Pignata, C. (2014). Intergenerational and intrafamilial phenotypic variability in 22q11.2 Deletion syndrome subjects. BMC Medical Genetics, 15(1), [1]. https://doi.org/10.1186/1471-2350-15-1

Intergenerational and intrafamilial phenotypic variability in 22q11.2 Deletion syndrome subjects. / Cirillo, Emilia; Giardino, Giuliana; Gallo, Vera; Puliafito, Pamela; Azzari, Chiara; Bacchetta, Rosa; Cardinale, Fabio; Cicalese, Maria P.; Consolini, Rita; Martino, Silvana; Martire, Baldassarre; Molinatto, Cristina; Plebani, Alessandro; Scarano, Gioacchino; Soresina, Annarosa; Cancrini, Caterina; Rossi, Paolo; Digilio, Maria C.; Pignata, Claudio.

In: BMC Medical Genetics, Vol. 15, No. 1, 1, 02.01.2014.

Research output: Contribution to journalArticle

Cirillo, E, Giardino, G, Gallo, V, Puliafito, P, Azzari, C, Bacchetta, R, Cardinale, F, Cicalese, MP, Consolini, R, Martino, S, Martire, B, Molinatto, C, Plebani, A, Scarano, G, Soresina, A, Cancrini, C, Rossi, P, Digilio, MC & Pignata, C 2014, 'Intergenerational and intrafamilial phenotypic variability in 22q11.2 Deletion syndrome subjects', BMC Medical Genetics, vol. 15, no. 1, 1. https://doi.org/10.1186/1471-2350-15-1
Cirillo, Emilia ; Giardino, Giuliana ; Gallo, Vera ; Puliafito, Pamela ; Azzari, Chiara ; Bacchetta, Rosa ; Cardinale, Fabio ; Cicalese, Maria P. ; Consolini, Rita ; Martino, Silvana ; Martire, Baldassarre ; Molinatto, Cristina ; Plebani, Alessandro ; Scarano, Gioacchino ; Soresina, Annarosa ; Cancrini, Caterina ; Rossi, Paolo ; Digilio, Maria C. ; Pignata, Claudio. / Intergenerational and intrafamilial phenotypic variability in 22q11.2 Deletion syndrome subjects. In: BMC Medical Genetics. 2014 ; Vol. 15, No. 1.
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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.",
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AU - Cirillo, Emilia

AU - Giardino, Giuliana

AU - Gallo, Vera

AU - Puliafito, Pamela

AU - Azzari, Chiara

AU - Bacchetta, Rosa

AU - Cardinale, Fabio

AU - Cicalese, Maria P.

AU - Consolini, Rita

AU - Martino, Silvana

AU - Martire, Baldassarre

AU - Molinatto, Cristina

AU - Plebani, Alessandro

AU - Scarano, Gioacchino

AU - Soresina, Annarosa

AU - Cancrini, Caterina

AU - Rossi, Paolo

AU - Digilio, Maria C.

AU - Pignata, Claudio

PY - 2014/1/2

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N2 - 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.

AB - 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.

KW - 22q11.2 deletion syndrome

KW - DiGeorge syndrome

KW - Immunodeficiency

KW - Phenotypic variability

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