Investigation of the epidemiology and prenatal diagnosis of holoprosencephaly in the North of England.

OBJECTIVE: This study was undertaken to provide epidemiologic data on the prevalence of holoprosencephaly and to assess the sensitivity of routine ultrasonographic screening in a low-risk population.

STUDY DESIGN: A population-based register of congenital abnormalities was used to identify reported cases of holoprosencephaly between 1985 and 1998. Sources included fetal losses, termination for fetal anomaly, stillbirths, and live births. Prenatal diagnoses and pregnancy outcomes were determined.

RESULTS: Sixty-eight cases of holoprosencephaly were found among 531,686 births. The total prevalence (including pregnancy terminations) was 1.2 cases/10,000 registered births, and the birth prevalence (affected live births and stillbirths at >24 weeks' gestation) was 0.49 cases/10,000 births. Prenatal diagnosis was achieved in 71% of cases, rising to 86% during the second half of the study period; the mean gestational age at diagnosis was 19.8 weeks' gestation. Chromosomal abnormalities (75% of which were trisomy 13) were present in 38% of cases in which a karyotype was established. All those with aneuploidy (80% diagnosed prenatally) had other nonfacial anomalies; additional anomalies were also common in the euploid group (61% diagnosed prenatally), with 90% having facial abnormalities and 70% having other abnormalities.

CONCLUSION: The prevalence of holoprosencephaly in second-trimester pregnancies was about 1 in 8000. Prenatal detection reached 86% with a routine anomaly scanning program. The etiology could usually be determined, which has important implications for recurrence risks.