Meckel-Gruber syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features and survival in Europe.

I Barisic, L Boban, Maria Loane, E Garne, D Wellesley, E Calzolari, Helen Dolk, MC Addor, JEH Bergman, P Braz, ES Draper, M Haeusler, B Khoshnood, K Klyngsoyr, A Pierini, A Queisser-Luft, J Rankin, A Rissmann, C Verellen-Dumoulin

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Abstract

Meckel–Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3±2.6 (range 11–36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.
LanguageEnglish
Pages746-752
Number of pages7
JournalEuropean Journal of Human Genetics
Volume23
Early online date3 Sep 2014
DOIs
Publication statusPublished - 2015

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Prenatal Diagnosis
Cross-Sectional Studies
Pregnancy
Survival
Encephalocele
Population
Registries
Nervous System Malformations
Cystic Kidney Diseases
Polydactyly
Kidney
Fetal Death
Liver
Live Birth
Genetic Testing
Counseling
Epidemiologic Studies
Early Diagnosis
Autopsy
Central Nervous System

Cite this

Barisic, I ; Boban, L ; Loane, Maria ; Garne, E ; Wellesley, D ; Calzolari, E ; Dolk, Helen ; Addor, MC ; Bergman, JEH ; Braz, P ; Draper, ES ; Haeusler, M ; Khoshnood, B ; Klyngsoyr, K ; Pierini, A ; Queisser-Luft, A ; Rankin, J ; Rissmann, A ; Verellen-Dumoulin, C. / Meckel-Gruber syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features and survival in Europe. In: European Journal of Human Genetics. 2015 ; Vol. 23. pp. 746-752.
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abstract = "Meckel–Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9{\%}) terminations of pregnancy after prenatal diagnosis, 13 (6.8{\%}) fetal deaths, 33 (17.3{\%}) live births. In addition to cystic kidneys (97.7{\%}), encephalocele (83.8{\%}) and polydactyly (87.3{\%}), frequent features include other central nervous system anomalies (51.4{\%}), fibrotic/cystic changes of the liver (65.5{\%} of cases with post mortem examination) and orofacial clefts (31.8{\%}). Various other anomalies were present in 64 (37{\%}) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2{\%}) are diagnosed prenatally at 14.3±2.6 (range 11–36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.",
author = "I Barisic and L Boban and Maria Loane and E Garne and D Wellesley and E Calzolari and Helen Dolk and MC Addor and JEH Bergman and P Braz and ES Draper and M Haeusler and B Khoshnood and K Klyngsoyr and A Pierini and A Queisser-Luft and J Rankin and A Rissmann and C Verellen-Dumoulin",
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Barisic, I, Boban, L, Loane, M, Garne, E, Wellesley, D, Calzolari, E, Dolk, H, Addor, MC, Bergman, JEH, Braz, P, Draper, ES, Haeusler, M, Khoshnood, B, Klyngsoyr, K, Pierini, A, Queisser-Luft, A, Rankin, J, Rissmann, A & Verellen-Dumoulin, C 2015, 'Meckel-Gruber syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features and survival in Europe.', European Journal of Human Genetics, vol. 23, pp. 746-752. https://doi.org/10.1038/ejhg.2014.174

Meckel-Gruber syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features and survival in Europe. / Barisic, I; Boban, L; Loane, Maria; Garne, E; Wellesley, D; Calzolari, E; Dolk, Helen; Addor, MC; Bergman, JEH; Braz, P; Draper, ES; Haeusler, M; Khoshnood, B; Klyngsoyr, K; Pierini, A; Queisser-Luft, A; Rankin, J; Rissmann, A; Verellen-Dumoulin, C.

In: European Journal of Human Genetics, Vol. 23, 2015, p. 746-752.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Meckel-Gruber syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features and survival in Europe.

AU - Barisic, I

AU - Boban, L

AU - Loane, Maria

AU - Garne, E

AU - Wellesley, D

AU - Calzolari, E

AU - Dolk, Helen

AU - Addor, MC

AU - Bergman, JEH

AU - Braz, P

AU - Draper, ES

AU - Haeusler, M

AU - Khoshnood, B

AU - Klyngsoyr, K

AU - Pierini, A

AU - Queisser-Luft, A

AU - Rankin, J

AU - Rissmann, A

AU - Verellen-Dumoulin, C

PY - 2015

Y1 - 2015

N2 - Meckel–Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3±2.6 (range 11–36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.

AB - Meckel–Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3±2.6 (range 11–36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.

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U2 - 10.1038/ejhg.2014.174

DO - 10.1038/ejhg.2014.174

M3 - Article

VL - 23

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EP - 752

JO - European Journal of Human Genetics

T2 - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

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