Epidemiology of acephalus/acardius monozygotic twins: New insights into an epigenetic causal hypothesis

Abstract

Apart from a series of 10 acephalus/acardius (Ac/Ac) cases described from a pathological point of view, and the analysis of a review of published cases, we have been unable to find any epidemiological studies on Ac/Ac. Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), we present here what seems to be the first epidemiological analysis of a consecutive series of the Ac/Ac type of monozygotic twins (MZT). Among a total of 2,281,604 consecutive births, 11 cases of Ac/Ac MZT were detected, giving a frequency of 0.48 per 100,000 births. However, we consider the period 1980-1985 as the baseline for our data, as in this period voluntary termination of pregnancy was not possible in Spain, and the frequency of Ac/Ac MZT was 0.49 per 100,000 births. Nonetheless, this frequency should be considered as a minimal estimation. The characteristics of these Ac/Ac cases indicate that they are more frequent in males (sex ratio 2.67). In addition, gestational age in Ac/Ac cases was 2.41 and 3.12 weeks lower than in malformed and control twins, respectively. Similarly, their mothers are 4.54 and 4.68 years younger than mothers of separate malformed and control twins, respectively. To understand the biological basis behind the occurrence of MZT in the context of recent observations, we evaluate the hypothesis that the epigenetic processes involved in the early cleavage of the embryo, and in blastocyst formation during development, may be implicated in twinning.