APPENDIX 6 EPIDEMOLOGY OF CORNELIA DE LANGE SYNDROME
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1 APPENDIX 6 EPIDEMOLOGY OF CORNELIA DE LANGE SYNDROME
2 Table 1. List of European registries contributing to the study: years of data, total number of births, prenatal diagnosis policy, followup of cases and involvement of clinical geneticist in diagnosis and coding of multiple congenital anomaly and/or syndrome cases Registry Country Years of data Total births (n) Routine US (n) Upper gestational age limit for TOP (weeks) Follow up of cases Involvement of clinical geneticist diagnosis STYRIA AUSTRIA year no no ANTWERPEN BELGIUM no upper limit until the diagnosis is complete most cases some cases HAINAUT BELGIUM no upper limit 1 year most cases most cases ZAGREB CROATIA week most cases all cases ODENSE DENMARK years some cases some cases AUVERGNE FRANCE no upper limit no data no data no data PARIS FRANCE no upper limit 1 week most cases no STRASBOURG FRANCE no upper limit 2 to 5 years most cases most cases MAINZ GERMANY no upper limit 10 years most cases no SAXONY-ANHALT GERMANY no upper limit 1 year some cases no CORK AND KERRY IRELAND not legal until the diagnosis is complete some cases no DUBLIN IRELAND not legal no routine follow up no no CAMPANIA ITALY year most cases most cases EMILIA ROMAGNA ITALY week - 1 year most cases all cases ISMAC ITALY until the diagnosis is complete all cases all cases NORTH EAST ITALY ITALY adulthood most cases all cases TUSCANY ITALY year some cases some cases MALTA MALTA no data not legal 1 year most cases no NORTH NETHERLANDS NETHERLANDS until the diagnosis is complete some cases most cases POLAND POLAND until the diagnosis is complete most cases all cases WIELKOPOLSKA POLAND until the diagnosis is complete most cases all cases SOUTH PORTUGAL PORTUGAL no data no data no data ASTURIAS SPAIN years most cases no BARCELONA SPAIN days some cases no BASQUE COUNTRY SPAIN year rare defects no VAUD SWITZERLAND no upper limit until the diagnosis is complete all cases all cases CARIS WALES UK no upper limit no data no data no data GLASGOW UK no upper limit no data no data no data NORTH THAMES UK no upper limit no data most cases some cases NORTHERN REGION UK no upper limit until the diagnosis is complete most cases some cases OXFORD UK no upper limit 1 year most cases most cases TRENT UK no upper limit until the diagnosis is complete most cases most cases WESSEX UK no upper limit 1 month most cases most cases TOTAL coding
3 Table 2. Prevalence and outcome of pregnancies of Cornelia de Lange syndrome in the EUROCAT birth defect registries, for period Monitored period Total births Total No of cases LB SB TOP Birth prevalence per Eurocat Registries ,604, Figure 1. Time of diganosis of classical form of Cornelia de Lange syndrome, EUROCAT, n= ,7 40 total cases (%) ,5 21,2 10,6 0 PND at birth 1st week 1st year
4 Table 3. Major anomalies associated with CdLS TYPE OF ANOMALY NO OF CASES % NERVOUS SYSTEM Microcephaly Holoprosencephaly Other EYE EAR NECK Short neck CONGENITAL HEART DISEASE Transposition of the great vessels Ventricular septal defect Atrial septal defect Atrioventricular canal defect Fallot's tetralogy Pulmonary valve stenosis Aortic valve stenosis Coarctation of aorta Other RESPIRATORY SYSTEM Choanal atresia Lung lobar anomaly ORO-FACIAL CLEFTS Cleft palate DIGESTIVE SYSTEM Duodenal stenosis Stenosis of other parts of small intestine Diaphragmatic hernia Other ABDOMINAL WALL DEFECTS Omphalocele GENITOURINARY SYSTEM Cystic kidney disease Congenital hydronephrosis Hypospadia Indeterminate sex 1 1.1
5 Other LIMB Limb reduction Upper limb reduction Lower limb reduction Unspecified limb reduction Complete absence of the upper limb Club foot - talipes equinovarus Hip dislocation and/or dysplasia Polydactyly Syndactyly Other MUSCULO-SKELETAL SYSTEM OTHER TOTAL
6 Figure 2. Malformations in Cornelia de Lange syndrome (n=93) 80,0 73,1 60,0 45,2 % 40,0 39,8 22,6 20,0 12,9 15,1 8,6 3,2 3,2 1,1 5,4 6,5 0,0 NERVOUS SYSTEM EYE EAR HEART DEFECTS RESPIRATORY SYSTEM CLEFT PALATE DIGESTIVE SYSTEM ABDOMINAL WALL DEFECTS GENITO-URINARY SYSTEM LIMB DEFECTS MUSCULO-SKELETAL SYSTEM OTHER
7 Table 4. Descriptive epidemiologic data on children with CdLS Variable No of cases Sex M 50 F 55 Maternal age, y n=106 < 20 4 (3.8%) (12.3%) (35.9%) (32.1%) (11.3%) (0.0%) Unknown 5 (4.7 %) Paternal age, y n=106 < 20 1 (0.9%) (4.7%) (17%) (19.8%) (10.4%) (3.8%) Unknown 46 (43.4%) Birth weight n=97 (liveborn) under (14.4%) (26.8%) (33%) (17. 6%) > (4.1%) unknown 4(4.1%) Gestational age, wk n= 97 (liveborn) < (30,9%) (62.9%) 42 1 (1%) unknown 5 (5.2%) Table 5. Sex distribution, maternal and paternal age according to the birth weight in live birth children with CdLS 2,500 g Birth weight >2,500 g Total M : F 0.98 (39/40) 0.54 (7/13) 0.87 maternal age 29.1 ± ± ± 4.7 paternal age 31.3 ± ± ± 4.9 limb anomalies No of cases = 47/61 (77.1%) No of cases = 7/18 (38.9%)
8 This report was produced by a contractor for Health & Consumer Protection Directorate General and represents the views of the contractor or author. These views have not been adopted or in any way approved by the Commission and do not necessarily represent the view of the Commission or the Directorate General for Health and Consumer Protection. The European Commission does not guarantee the accuracy of the data included in this study, nor does it accept responsibility for any use made thereof.
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