Le diagnostic anténatal de la délétion 22q11.2 : une étude collaborative à propos de 272 fœtus

Objective: The 22q11.2 deletion (del22q11.2) is the most common microdeletion. We performed a collaborative retrospective analysis in France of prenatal diagnoses and outcomes of fetuses carrying the del22q11.2. Methods: A total of 272 fetuses were included. Data on prenatal diagnosis, ultrasound findings, pathological features, outcomes and inheritance were analyzed. Results: The mean time of prenatal diagnosis was 25.6±6 w.g. Most of the diagnoses (86.8%) were prompted by abnormal ultrasound findings (heart defects (HDs), in 83.8% of cases). On fetal autopsy, HDs were again the most common disease feature but thymus, kidney abnormalities and facial dysmorphism were also described. The deletion was inherited in 27% of cases. Termination of pregnancy (TOP) occurred in 68.9% of cases and did not appear to depend on the inheritance status. However, an early diagnosis was associated with a higher TOP rate. Conclusion: This is the largest cohort of prenatal del22q11.2 diagnoses. As in postnatally diagnosed cases, HDs were the most frequently observed abnormalities. However, thymus and kidney abnormalities and polyhydramnios should also be screened for in the prenatal diagnosis of del22q11.2. Only the time of diagnosis appeared to be strongly associated with the pregnancy outcome: the earlier the diagnosis, the higher the TOP rate.Objectifs : La délétion 22q11.2 (del22q11.2) est la microdélétion la plus fréquente dans l’espèce humaine. Nous avons effectué, en France, une analyse rétrospective collaborative portant sur le diagnostic prénatal des fœtus porteurs de la del22q11.2. Méthodes : Un total de 272 fœtus a été inclus. Les données sur le diagnostic prénatal, les résultats de l'échographie, les caractéristiques pathologiques, l’issue de grossesse et la transmission parentale ont été analysés. Résultats : Le terme moyen du diagnostic prénatal était de 25,6 ± 6 SA. La plupart des diagnostics (86,8%) ont été réalisés suite à l’observation d’anomalies à l'échographie (anomalies cardiaques (AC), dans 83,8% des cas). Sur l’examen fœtopathologique, les AC étaient également les anomalies les plus communes, mais des anomalies thymiques et rénales et une dysmorphie faciale étaient aussi décrites. La délétion était héritée dans 27% des cas. Une interruption médicale de grossesse (IMG) a été réalisée dans 68,9% des cas. Si le recours à une IMG ne semble pas dépendre du caractère hérité ou non de l’anomalie, la précocité du diagnostic semble être associée à un taux plus élevé d’IMG. Conclusion : Il s'agit de la plus grande cohorte de diagnostics prénataux de la del22q11.2. Comme dans les cas diagnostiqués après la naissance, les AC sont les anomalies les plus fréquemment observées. Les anomalies du thymus et des reins, ainsi que l’hydramnios devraient également être recherchés en cas de suspicion de diagnostic prénatal de del22q11.2. Seul le moment du diagnostic semble être étroitement associé à l'issue de la grossesse : plus le diagnostic est précoce, plus le taux d’IMG augmente

A French collaborative survey of 272 fetuses with 22q11.2 deletion: ultrasound findings, fetal autopsies and pregnancy outcomes

International audienceObjective: The 22q11.2 deletion (del22q11.2) is one of the most common microdeletions. We performed a collaborative, retrospective analysis in France of prenatal diagnoses and outcomes of fetuses carrying the del22q11.2.Methods: A total of 272 fetuses were included. Data on prenatal diagnosis, ultrasound findings, pathological features, outcomes and inheritance were analyzed.Results: The mean time of prenatal diagnosis was 25.6 ± 6 weeks of gestation. Most of the diagnoses (86.8%) were prompted by abnormal ultrasound findings [heart defects (HDs), in 83.8% of cases]. On fetal autopsy, HDs were again the most common disease feature, but thymus, kidney abnormalities and facial dysmorphism were also described. The deletion was inherited in 27% of cases. Termination of pregnancy (TOP) occurred in 68.9% of cases and did not appear to depend on the inheritance status. However, early diagnosis was associated with a higher TOP rate.Conclusion: This is the largest cohort of prenatal del22q11.2 diagnoses. As in postnatally diagnosed cases, HDs were the most frequently observed abnormalities. However, thymus and kidney abnormalities and polyhydramnios should also be screened for in the prenatal diagnosis of del22q11.2. Only the time of diagnosis appeared to be strongly associated with the pregnancy outcome: the earlier the diagnosis, the higher the TOP rate.© 2014 John Wiley & Sons, Ltd

Prenatal diagnosis of 24 cases of microduplication 22q11.2: an investigation of phenotype-genotype correlations.

International audienceObjective - 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. Conclusion - 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

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

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