Congenital hydranencephalic-hydrocephalic syndrome with proliferative vasculopathy: a possible relation with mitochondrial dysfunction

Abstract

We report the case of a fetus aborted at gestation week 20 because of hydranencephalic-hydrocephalic syndrome. The fetus was the third pregnancy of a nonconsanguineous couple whose first child exhibited congenital hydranencephalic-hydrocephalic syndrome associated with muscle histology findings consistent with mitochondrial cytopathy and deficiency of complexes III and IV of the respiratory chain and whose second pregnancy had terminated in an elective abortion on detection of progressive hydrocephalus at gestation week 19. The third pregnancy had a normal course according to obstetric and ultrasonography examinations performed at gestation weeks 5, 10, and 15, and negative results were obtained in standard serologic and polymerase chain reaction (PCR) tests for prenatal infections of the mother. However, the ultrasonography examination at gestation week 18 revealed hydrocephalus, in response to which the parents requested an abortion, which was performed at gestation week 20; the fetus was male and with no evident external malformations. Histopathologic studies of the brain and medulla oblongata revealed proliferative vasculopathy (glomeruloid vessels, intracytoplasmic inclusions, and microcalcifications) and intracytoplasmic inclusions in the voluntary muscle. Microbiologic and PCR tests of hepatic and spleen tissue were negative for prenatal infections. In view of the precedent of a sister with mitochondrial dysfunction, these findings raise the pos sibility that at least some cases of familial syndrome of congenital hydranencephalic-hydrocephalic syndrome with proliferative vasculopathy can be attributed to alterations in the mitochondrial respiratory chain.