title: Meckel-Gruber Syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe.
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.
authors.affiliation: Children's Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Barisic
authors.affiliation: Children's Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Ljubica
authors.initials: L
authors.lastname: Boban
authors.affiliation: EUROCAT Central Registry, University of Ulster, Ulster, Northern Ireland.
authors.forename: Maria
authors.initials: M
authors.lastname: Loane
authors.affiliation: Pediatric Department, Hospital Lillebaelt, Kolding, Denmark.
authors.forename: Ester
authors.initials: E
authors.lastname: Garne
authors.affiliation: Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Wellesley
authors.affiliation: Registro IMER, Unita di Terapia Intensiva Neonatale e Neonatologia, Azienda Ospedaliero-Universitaria di Ferrara, Ferrara, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Calzolari
authors.affiliation: EUROCAT Central Registry, University of Ulster, Ulster, Northern Ireland.
authors.forename: Helen
authors.initials: H
authors.lastname: Dolk
authors.affiliation: Registre vaudois des anomalies congénitales, Service de génétique médicale, Lausanne, Switzerland.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Addor
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jorieke Eh
authors.initials: JE
authors.lastname: Bergman
authors.affiliation: Departamento de Epidemiologia, Instituto Nacional de Saude Doutor Ricardo Jorge, Lisbon, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Braz
authors.affiliation: Department of Epidemiology Public Health, University of Leicester, Leicester, UK.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Draper
authors.affiliation: Styrian Malformation Registry, University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Haeusler
authors.affiliation: Paris Registry of Congenital Malformations, INSERM U953, Maternite de Port-Royal, Paris, France.
authors.forename: Babak
authors.initials: B
authors.lastname: Khoshnood
authors.affiliation: Department of Public Global Health and Primary Health Care, Medical Birth Registry of Norway, Norwegian Institute of Public Health, University of Bergen, Bergen, Norway.
authors.forename: Kari
authors.initials: K
authors.lastname: Klungsoyr
authors.affiliation: CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pierini
authors.affiliation: Universitätskinderklinik Mainz, Mainz, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Queisser-Luft
authors.affiliation: Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Rankin
authors.affiliation: Malformation Monitoring Centre Saxony-Anhalt, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Rissmann
authors.affiliation: Institut de Pathologie et de Génétique, Charleroi, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Verellen-Dumoulin
mesh_terms: D002925:Ciliary Motility Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality; D004677:Encephalocele / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality; D005060:Europe; D005260:Female; D005820:Genetic Testing / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D007690:Polycystic Kidney Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000706:statistics & numerical data*; D015995:Prevalence; D012174:Retinitis Pigmentosa