Associated anomalies in multi-malformed infants with cleft lip and palate: An epidemiologic study of nearly 6 million births in 23 EUROCAT registries


  • How to cite this article: Calzolari E, Pierini A, Astolfi G, Bianchi F, Neville AJ, Rivieri F, and EUROCAT Working Group. 2007. Associated anomalies in multi-malformed infants with cleft lip and palate: An epidemiologic study of nearly 6 million births in 23 EUROCAT registries. Am J Med Genet Part A 143A:528–537.

  • The EUROCAT Registries that participated in the study are: Styria, Austria; Martin Haeusler, Hainaut, Belgium: Yves Gillerot, Zagreb, Croatia: Ingeborg Barisic, Odense, Denmark; Ester Garne, Paris, France; Catherine De Vigan, Strasbourg, France; Claude Stoll, Saxony-Anhalt, Germany; Simone Poetzsch, Dublin, Ireland; Bob McDonnell, Galway, Ireland; David Lillis, Campania, Italy; Gioacchino Scarano, Emilia Romagna, Italy; Elisa Calzolari, Mainz Germany; Annette Queisser-Luft, North East Italy; Romano Tenconi, Tuscany, Italy; Fabrizio Bianchi, Malta; Miriam Gatt, South Portugal; Maria Feijoo, Asturias, Spain; Carmen Mosquera-Tenreiro, Barcelona, Spain; Joaquin Salvador, Basque Country, Spain; Blanca Gener, Vaud Switzerland; Marie-Claude Addor, North Thames UK; Lenore Abramsky, North Netherlands; Hermien De Walle, Glasgow, UK; David Stone. Maria Loane, of the EUROCAT central registry, extracted the data.


We studied 5,449 cases of cleft lip (CL) with or without cleft palate (CL/P) identified between 1980 and 2000 from the EUROCAT network of 23 registers (nearly 6 million births) in 14 European countries. We investigated specific types of defect sassociated with clefts. Among CL/P cases (prevalence = 9.1 per 10,000), 1,996 (36.6%) affected only the lip (CL) and 3,453 (63.4%) involved CL and palate (CLP). A total of 3,860 CL/P cases (70.8%) occurred as isolated anomalies and 1,589 (29.2%) were associated with other defects such as multiple congenital anomalies of unknown origin (970), chromosomal (455) and recognized syndromes (164). Associated malformations were more frequent in infants who had CLP (34.0%) than in infants with CL only (20.8%). Among multi-malformed infants, 2 unrelated anomalies were found in 351 cases, 3 in 242 cases, and 4 or more in 377 cases. Among 5,449 CL/P cases, 4,719 were live births (LB) (86.6%), 203 stillbirths (SB) (3.7%), while 508 (9.3%) were terminations of pregnancy (ToP). CL/P occurred significantly more frequently in males (M/F = 1.70), especially among total isolated cases (M/F = 1.87) and CLP isolated cases (M/F = 1.92). The study confirmed that musculoskeletal, cardiovascular, and central nervous system defects are frequently associated with CL/P. An association with reduction anomalies of the brain was found. This association suggests that clinicians should seek to identify structural brain anomalies in these patients with CL/P as the potential functional consequences may be important for rehabilitation and clinical management. © 2007 Wiley-Liss, Inc.