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

[22q11.2 deletion syndrome]

22 q 11 .2 deletion syndrome (22 q 11 .2 DS ) 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 22 q 11 .2 deletion .Thirty -two 22 q 11 .2 DS subjects among 26 families were enrolled .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 .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 .

Diseases
Validation

Diseases presenting "low rate" symptom

22q11.2 deletion syndrome

erythropoietic protoporphyria

junctional epidermolysis bullosa

thoracic outlet syndrome

trochlear dysplasia

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