A preterm infant with anaemia and left leg mild hemihypertrophy (Discussion and Diagnosis)

Abstract

The Case Presentation can be found on page 1192. DISCUSSION The clinical course suggested placental mesenchymal dysplasia (PMD) that was confirmed by pathological examination of the placenta. Genetic test confirmed Beckwith– Wiedemann syndrome (BWS, paternal uniparental disomy). First described in 1991 by Moscoso et al. (1), PMD is characterized by placentomegaly with multicystic ‘grapelike vesicles’, similar to a partial mole at ultrasound scan and macroscopic examinations. There is a diffuse hydropic degeneration of chorionic villi and a absence of trophoblastic proliferation (1,2). In contrast to a hydatidiform mole, PMD may coexist with a viable foetus. Final diagnosis of PMD is made by histologic examination of the placenta. Most cases of PMD in early pregnancy are diagnosed by prenatal ultrasonography done for routine prenatal checkup, although it has been associated with pre-eclampsia (3,4). The incidence of PMD is unknown. A Japanese study estimated an incidence of 0.02% of placentas examined (3,5). Recently, a Canadian review (6) with more than 95 000 placentas examined, found two cases, 0.002 ⁄%.There is a marked female predominance in PMD (3), but this is much less apparent in cases of BWS which has a ratio of 1.6 female to male compared to PMD without BWS 4.33:1. Foetal morbidity and mortality are more frequent (3), as IUGR, intrauterine foetal demise, polyhydramnios, prematurity, BWS (20–30% of cases) and anaemia–thrombocytopenia (7) secondary to placental haemolysis. It has also been associated with 13 trisomy, other mesenchymal tumours, as hepatic, vascular or pulmonary hamartomas (8), serous cystadenoma of pancreas and congenital adrenal hyperplasia, suggesting a common defect in placental and embryonic mesoderm. Pham et al. (3). stated that among all cases without BWS, 50% had IUGR and 43% had intrauterine foetal demise or neonatal death. IUGR (9) and intrauterine foetal demise are explained by hypoxia secondary to vascular thrombosis and reduced gas exchange area. Foetuses with BWS had normal weight percentiles. Aetiology of PMD remains unclear. Hypoxia and hypoperfusion may give rise to the phenotypic findings in the placenta with PMD as during hypoxia, fibroblasts are stimulated to produce increased connective tissue fibres with subsequent increased production of vascular endothelial growth factor by villous macrophages leading to angiogenesis (10). Genetically, most PMD are diploid, while 70–80% of partial moles are triploid. Some cases of PMD have been associated to androgenetic ⁄biparental mosaicism (11,12), with the hypothesis that biparent cell line gives rise to normal structures (foetus, amnion and trophoblast) and androgenetic cell line would result in the chorion and mesenchymal villi with the characteristic changes of the DMP. Such mosaicism arose as a result of failure of the maternal genome to duplicate before the first cleavage with normal duplication and segregation of the paternal genome, resulting in two daughter cells, one with normal biparental genes and another with only paternal genes that became ‘diploid’ through endoreduplication. The association with BWS could be explained because androgenetic cells express a biallelic paternal IGF2 gene from 11p15.5. Studies have shown a female predominance in cases of PMD, and it is speculated that there is a relationship with the endothelial growth factor gene deletions in the X-chromosome (5,13,14). Acta Paediatrica ISSN 0803–5253