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

We report the case of a fetus aborted at gestation week 20 because of hydra nencephalic-hydrocephalic syndrome. The fetus was the third pregnancy of a nonconsanguineous couple whose first child exhibited congenital hydranencep halic-hydrocephalic syndrome associated with muscle histology findings cons istent with mitochondrial cytopathy and deficiency of complexes III and IV of the respiratory chain and whose second pregnancy had terminated in an el ective abortion on detection of progressive hydrocephalus at gestation week 19. The third pregnancy had a normal course according to obstetric and ult rasonography examinations performed at gestation weeks 5, 10, and 15, and n egative results were obtained in standard serologic and polymerase chain re action (PCR) tests for prenatal infections of the mother. However, the ultr asonography examination at gestation week 18 revealed hydrocephalus, in res ponse to which the parents requested an abortion, which was performed at ge station week 20; the fetus was male and with no evident external malformati ons. Histopathologic studies of the brain and medulla oblongata revealed pr oliferative vasculopathy (glomeruloid vessels, intracytoplasmic inclusions, and microcalcifications) and intracytoplasmic inclusions in the voluntary muscle. Microbiologic and PCR tests of hepatic and spleen tissue were negat ive for prenatal infections. In view of the precedent of a sister with mito chondrial dysfunction, these findings raise the possibility that at least s ome cases of familial syndrome of congenital hydranencephalic-hydrocephalic syndrome with proliferative vasculopathy can be attributed to alterations in the mitochondrial respiratory chain.