Alterations of the fetal extracellular matrix in the nuchal oedema of Down's syndrome

Abstract

Elevations in the lateral and dorsal neck region are known to be highly correlated with chromosomal aberrations in human fetuses. However, the morphology of the elevations is poorly described. Only in the case of Turner's syndrome has lymphatic vessel formation been shown to be deficient leading to swellings in the nuchal area. In Down's syndrome, non-echogenic nuchal oedemata can be visualized in ultrasound scan between the 10th and 15th week of gestation. In the present study, alterations in the extracellular matrix (ECM) of the skin in trisomy 21 fetuses were found to be the morphological basis of the nuchal oedema. The distribution of collagen type VI differs from that in normal fetuses, both in nuchal and leg skin. Collagen VI forms a denser mesh in trisomy 21 than in normal fetal skin, hyaluronan (HA) being the main glycosaminoglycan (GAG) component as judged from the appearance of the TEM precipitate after fixation in the presence of tannic acid. Nuchal oedema in Down's syndrome is therefore found to be an interstitial oedema. The interstitial fluid is bound to HA, leading to a swelling of the fetal dermis. No cysts or dilated vessels were found in the oedematous tissue. The presence of a high amount of HA during development can influence the behaviour of migrating cell populations, which might have a bearing on the pathogenesis of Down's syndrome.