Descriptive epidemiology of holoprosencephaly and arhinencephaly in metropolitan Atlanta, 1968–1992

Abstract

We report the descriptive epidemiology of holoprosencephaly and arhinencephaly using data from the Metropolitan Atlanta Congenital Defects Program, a population-based birth defects surveillance system with multiple sources of ascertainment. From 1968-1992, we ascertained 63 cases of holoprosencephaly and arhinencephaly from approximately 734,000 births, for a birth prevalence of 0.86 per 10,000. Thirteen case infants with holoprosencephaly and four case infants with arhinencephaly were categorized as having syndromes. Of the case infants with non-syndromic holoprosencephaly, 55% had malformations not attributable to the underlying brain defect. The rate of holoprosencephaly and arhinencephaly increased from 0.58 per 10,000 during 1968-1972 to 1.2 per 10,000 during 1988-1992 (P for trend = 0.016). Rates were higher for females than for males (risk ratio = 1.45, 95% C.I. 0.88-2.41) and higher for nonwhites than for whites (risk ratio = 1.74, 95% C.I. 1.06-2.86). There was a U-shaped distribution of risk associated with maternal age with a slightly increased risk for younger women (risk ratio for maternal age < 20 years, compared with age 25-29 years = 1.68, 95% C.I. 0.77-3.62) and older women (risk ratio for maternal age > 34 years, compared with age 25-29 years = 2.30, 95% C.I. 0.93-5.7), but this was not statistically significant. The increased risk in the older age group could be largely explained by the presence of cases with autosomal trisomies. Neonatal mortality was higher for infants with malformations that were not attributable to the underlying brain defect and for infants with syndromes than for infants with isolated holoprosencephaly. This analysis is the first population-based study with long-term data on this rare defect. Further epidemiologic studies will be necessary to assess the risk factors for holo-prosencephaly and arhinencephaly.

Clinical Features and Outcomes of Holoprosencephaly in Korea

“…This prenatal diagnosis often results in the termination of pregnancy, depending on the severity of disease. The higher incidence of holoprosencephaly among females was previously reported [19,21], and our results also yielded consistent findings, although phenotypic sex was not mentioned in seven cases. The female predominance may be explained by the higher likelihood of males to abort spontaneously [21].…”

Epidemiology of central nervous system malformations in South-Eastern Hungary

“…Non-craniofacial abnormalities can occur in more than half of the cases without chromosomal abnormalities (25). The ratio was similar in our study, 4…”

“…cases were found in a series of 63 patients in the literature (25). The only case associated with maternal diabetes in our series represents a similar ratio despite the small number of cases.…”

“…The range of craniofacial abnormalities in the patients in this study extended from severe defects with cyclopia to milder forms of midfacial dysmorphic features described in the literature (25). Non-craniofacial abnormalities can occur in more than half of the cases without chromosomal abnormalities (25).…”

Holoprosencephaly—Report of two cases

“…Rassmussen et al [4] found a birth prevalence of 0.72 cases per 10,000 births in Metropolitan Atlanta from 1968 to 1992. Its incidence is increased 60-fold among studies of aborted human embryos, therefore indicating that most cases are eliminated prenatally [2].…”