Epidemiology of holoprosencephaly and phenotypic characteristics of affected children: New York state, 1984–1989

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Abstract
Holoprosencephaly is a congenital defect of the median structures of the brain and face. The epidemiology is poorly known due to the paucity of population‐based studies. This study describes the epidemiology of holoprosencephaly in a large population, using cases identified through the New York State Congenital Malformations Registry, and born in 1984–1989. We describe the craniofacial abnormalities present, their frequency, and their cooccurrence, and we examine the correspondence between the severity of craniofacial abnormalities, chromosomal abnormalities, and severity of the brain defect. Liveborn cases totaled 78, yielding a prevalence of 4.8 per 100,000 live births. Prevalence among girls was nearly double that in boys, and was 4.2 times higher among infants of mothers under age 18 compared to infants of older mothers. Only 9.8% of all cases had no craniofacial abnormalities other than the brain defect. Eye malformations were present in 76.8%, nose malformations in 69.5%, ear malformations in 50%, and oral clefts in 41.5%. These malformations arise at different times during gestation. The variability in patterns of cooccurrence suggests variability in the developmental pathways and/or timing of developmental derangements which result in holoprosencephaly. This, in turn, is consistent with a model of multiple causes. Children with alobar holoprosencephaly tended to have the most severe craniofacial anomalies, but the correspondence was not 100%. Craniofacial phenotype does not consistently discriminate between cytogenetically normal and abnormal cases. Am. J. Med. Genet. 73:217–226, 1997.