Significance of cardiovascular malformations in cystic hygroma: a new interpretation of the pathogenesis

Am J Med Genet. 1989 Dec;34(4):489-501. doi: 10.1002/ajmg.1320340408.


Fetuses with cystic hygroma or loose skin of the neck were studied chromosomally and phenotypically to clarify the relation between neck abnormality and cardiovascular malformations. Of 12 fetuses, 9 had chromosome abnormalities: 4 with 45,X, 3 with trisomy 21, one each with trisomy 13, dup 6q. One had normal chromosomes. Two cases, in which chromosome analysis was unsuccessful, were morphologically suspected to be trisomy 13. Nine of the 12 fetuses had either bilateral cystic hygroma of the neck (7 cases) or nuchal bleb (2 cases: trisomy 13 and dup 6q). Two of the 3 remaining cases (trisomy 21) had loose skin of the neck, and one had edematous swelling of the skin of the neck. Except for the last case of trisomy 21, 11 fetuses (91.7%) had severe and/or rare cardiovascular malformations. They were divided into 3 major groups: a) spectrum of hypoplastic left heart syndrome (45,X and dup 6q), b) double outlet right ventricle, agenesis of semilunar valve (trisomy 13), and c) abnormality of atrioventricular orifice or valves (trisomy 21). One fetus with normal chromosomes had persistent left superior vena cava instead of absent right one and calcification of myocardium. Histological observation of edematous skin demonstrated the abnormal distribution of lymph vessels, including their absence. Some cases showed hypoplastic thymus. To integrate the findings of the present study and the descriptions in the literature, a pathogenesis is hypothesized in relation to migration of neural crest cells and extracellular matrix.

MeSH terms

  • Abnormalities, Multiple / pathology*
  • Chromosome Aberrations / pathology*
  • Chromosome Disorders
  • Chromosomes, Human, Pair 13
  • Down Syndrome
  • Female
  • Fetal Diseases / genetics
  • Fetal Diseases / pathology*
  • Heart Defects, Congenital / genetics
  • Heart Defects, Congenital / pathology*
  • Humans
  • Lymphangioma / genetics
  • Lymphangioma / pathology*
  • Male
  • Phenotype
  • Pregnancy
  • Trisomy