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Embryonic holoprosencephaly: pathology and phenotypic variability


  • Shigehito Yamada

    Corresponding author
    1. Congenital Anomaly Research Center and
    2. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan
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  • Shigehito Yamada received the 2005 Young Investigator’s Award of the Japanese Teratology Society for the research described in this paper. Grant information and grant numbers: Grant sponsor: Japanese Ministry of Education, Culture, Sports, Science and Technology; Grant number: 13557001, 13470003; Grant sponsor: Japanese Ministry of Health, Labour and Welfare; Grant number: 14A-4.

Shigehito Yamada, MD, Congenital Anomaly Research Center, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan. Email:


ABSTRACT  Holoprosencephaly (HPE) is one of the major brain anomalies caused by the failure of cleavage of the prosencephalon during the early stage of development. Over 200 cases of HPE in the Kyoto Collection of Human Embryos were observed grossly and histologically, with special emphasis on the anomalies of the brain, face and eye. The facial anomalies of HPE human embryos after Carnegie stage (CS) 18 could be classified into cyclopia, synophthalmia, ethmocephaly, cebocephaly, and premaxillary agenesis, similarly as the classical classification for postnatal cases. On the other hand, HPE embryos at CS 13–17 showed some characteristic facies which are different from those in older embryos. In the present paper, pathology and phenotypic variability in HPE embryos were discussed from the embryopathological point of view. Recently, the molecular mechanism of HPE has been clarified by the techniques of gene manipulation, and various HPE genes have been identified by gene analysis of familial HPE cases. HPE is one of the major CNS anomalies which have been extensively studied and provides a clue to the mechanisms of normal and abnormal development of craniofacial structures.