Nationwide epidemiological survey of holoprosencephaly in Japan

BACKGROUND: Holoprosencephaly (HPE) is a congenital malformation with an estimated prevalence of 0.10-6.06 per 10,000 births, but with no nationwide data specific to Japan. METHODS: This nationwide retrospective questionnaire survey was conducted from 2011 to 2013. All 467 training hospitals for perinatal and neonatal care certified by the Japan Society of Perinatal and Neonatal Medicine were contacted. The birth prevalence rate (BPR) was assessed from the primary survey and clinical characteristics from the secondary survey. RESULTS: We received valid responses from 253 hospitals in the primary survey (54.6%). Of 390,342 live births, 60 were diagnosed with HPE (23 males and 37 females), resulting in an actual BPR of 1.54 per 10,000 live births. The point estimate for HPE cases was 100 (95% confidential interval [CI]: 80.7-120), and the estimated BPR of HPE was calculated to be 0.32 per 10,000 live births (95% CI: 0.26-0.38) based on 3,117,853 live births according to the Japanese national statistics during the study period. In the secondary survey, we obtained data for 49 cases (19 males and 30 females). Of these, 20 were alobar (40.8%), 20 were semilobar (40.8%), 5 were lobar (10.4%), and 4 were of unknown types. Genetic examination was performed in 37 of the 49 HPE patients and revealed that chromosomes 13, 18, and 7 were affected in 8, 6, and 4 patients, respectively. CONCLUSION: This is the most extensive survey on holoprosencephaly to date in Japan. The estimated BPR was consistent with that reported in previous research.