Geoffrey Machin

Five hundred consecutive cases with histologic chorioamnionitis and umbilical cord inflammation were analyzed to develop a staging system for funisitis and to correlate stage of funisitis with stage of chorioamnionitis in order to estimate the timing of various stages of funisitis. Funisitis progresses through venous involvement (with or without Wharton's jelly inflammation) to arterial involvement without Wharton's jelly and then full involvement of all three vessels and surrounding Wharton's jelly. Arterial involvement and full funisitis are strongly associated with stage III/IV chorioamnionitis, and imply a significant time interval following the onset of amniotic cavity inflammation.

Monozygotic twins (MZ) are rarely absolutely “identical.” This review discusses the types of genetic/epigenetic and prenatal environmental post‐zygotic mechanisms that cause discordance within such twin pairs. Some of these mechanisms—ranging from heterokaryotypia to skewed X‐chromosome inactivation—may cause extreme discordance, but these extremes are merely the more emphatic examples of discordance that, to some degree, underlies the majority of MZ twin pairs. Because of the entrenched misconception that MZ twins are necessarily identical, many MZ twin pairs are mistakenly designated as dizygotic (DZ). Clinical benefits to accurate zygosity determination include correct solid organ transplantation matching, if one twin requires donation for a non‐genetically mediated disease; the opportunity of preventive management for disorders that do not manifest synchronously; and better counseling to parents regarding their individually unique, and often psychologically puzzling, twin offspring. In twin pairs with complex and confusing biological origins, more detailed zygosity testing may be required. For example, intermediate trigametic and tetragametic chimeric dizygotic twins are reviewed, some of whom are, nevertheless, monochorionic (MC). Because of inter‐fetal vascular anastomoses in MC twins, genetic results from blood samples may not accurately reflect discordance in solid organs. Previously, it was thought that MZ twinning was some sort of embryological fluke. However, familial monozygotic twinning is more common than suggested by the literature. Seven new families are presented in an accompanying paper. Despite the difficulties and dangers of twin pregnancy (especially so for MC twins), human twinning persists, and continues to both challenge and fascinate parents, clinicians and geneticists.

Seven families contained 19 MZ twin pairs (2.7 pairs/family), diagnosed by low‐stringency variable number tandem repeats in DNA from placental tissue or blood. Chorion status was known in 10 pairs, 6 dichorionic, 4 monochorionic. Sex ratio was equal. Autosomal dominant inheritance is apparent.

Maternal floor infarction (MFI), massive perivillous fibrin deposition (MPVFD), and fetal thrombotic vasculopathy (FTV) are specific placental lesions with associations to recurrent adverse fetal outcomes and with maternal thrombophilia. We studied the frequency of a range of acquired and genetic maternal thrombophilias in MFI (40 cases), MPVFD (87 cases), FTV (7 cases), and FTV+MPVFD (4 cases). Thrombophilias were identified in 16 (40%), 20 (23%), 5 (71%), and 2 (50%) of these lesions, respectively. Seventy-seven percent of the identified thrombophilias were genetic, and 23% were acquired. The most common genetic thrombophilia was protein S deficiency, which constituted 14 of the 36 genetic thrombophilias (39%). We advocate full maternal thrombophilia testing when the diagnosis of MFI, MPVFD, and FTV is made by placental pathology examination. Because of the possible contribution of paternal thrombophilic mutations to the fetal genotype, it would be desirable to test the whole family as well.