Cyclopia: An epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research

Cyclopia is characterized by the presence of a single eye, with varying degrees of doubling of the intrinsic ocular structures, located in the middle of the face. It is the severest facial expression of the holoprosencephaly (HPE) spectrum. This study describes the prevalence, associated malformations, and maternal characteristics among cases with cyclopia. Data originated in 20 Clearinghouse (ICBDSR) affiliated birth defect surveillance systems, reported according to a single pre-established protocol. A total of 257 infants with cyclopia were identified. Overall prevalence was 1 in 100,000 births (95%CI: 0.89-1.14), with only one program being out of range. Across sites, there was no correlation between cyclopia prevalence and number of births (r=0.08; P=0.75) or proportion of elective termination of pregnancy (r=-0.01; P=0.97). The higher prevalence of cyclopia among older mothers (older than 34) was not statistically significant. The majority of cases were liveborn (122/200; 61%) and females predominated (male/total: 42%). A substantial proportion of cyclopias (31%) were caused by chromosomal anomalies, mainly trisomy 13. Another 31% of the cases of cyclopias were associated with defects not typically related to HPE, with more hydrocephalus, heterotaxia defects, neural tube defects, and preaxial reduction defects than the chromosomal group, suggesting the presence of ciliopathies or other unrecognized syndromes. Cyclopia is a very rare defect without much variability in prevalence by geographic location. The heterogeneous etiology with a high prevalence of chromosomal abnormalities, and female predominance in HPE, were confirmed, but no effect of increased maternal age or association with twinning was observed.Fil: Orioli, Ieda Maria. Instituto de Biologia; Brasil. Instituto Nacional de Genética Médica Populacional; BrasilFil: Amar, Emmanuelle. Rhone-alps Registry Of Birth Defects Remera; FranciaFil: Bakker, Marian K.. University of Groningen; Países BajosFil: Bermejo Sánchez, Eva. Instituto de Salud Carlos III; Brasil. Centro de Investigación Biomédica En Red de Enfermedades Raras; BrasilFil: Bianchi, Fabrizio. Consiglio Nazionale delle Ricerche; ItaliaFil: Canfield, Mark A.. Texas Department Of State Health Services; Estados UnidosFil: Clementi, Maurizio. Università di Padova; ItaliaFil: Correa, Adolfo. Centers for Disease Control and Prevention; BrasilFil: Csáky Szunyogh, Melinda. National Center for Healthcare Audit and Inspection; HungríaFil: Feldkamp, Marcia L.. Utah Department Of Health; Estados Unidos. University Of Utah Health Sciences; Estados UnidosFil: Landau, Danielle. Soroka University Medical Center; IsraelFil: Leoncini, Emanuele. Centre Of The International Clearinghouse For Birth Defects Surveillance And Research; ItaliaFil: Li, Zhu. Peking University Health Science Center; ChinaFil: Lowry, R. Brian. Alberta Congenital Anomalies Surveillance System; CanadáFil: Mastroiacovo, Pierpaolo. Centre Of The International Clearinghouse For Birth Defects Surveillance And Research; ItaliaFil: Morgan, Margery. the Congenital Anomaly Register for Wales; Reino UnidoFil: Mutchinick, Osvaldo M.. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Rissmann, Anke. Otto-von-Guericke-Universität Magdeburg; AlemaniaFil: Ritvanen, Annukka. National Institute For Health And Welfare; FinlandiaFil: Scarano, Gioacchino. General Hospital G. Rummo Benevento; ItaliaFil: Szabova, Elena. Slovak Medical University; EslovaquiaFil: Castilla, Eduardo Enrique. Instituto Nacional de Genética Médica Populacional; Brasil. Centro de Educación Medica E Invest.clinicas; Argentina. Fundación Oswaldo Cruz; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin