Valproic acid embryopathy: report of two siblings with further expansion of the phenotypic abnormalities and a review of the literature

Am J Med Genet. 2001 Jan 15;98(2):168-75.

Abstract

Fetal Valproate Syndrome (FVS) results from prenatal exposure to valproic acid (VPA). It is characterized by a distinctive facial appearance, a cluster of minor and major anomalies, and central nervous system dysfunction. In this study, two siblings who were exposed to monotherapy with VPA are described with documentation of long-term follow up. Both children had craniofacial findings, multiple systemic and orthopedic abnormalities, an overgrowth pattern, and developmental deficits. The literature from 1978-2000 is reviewed. A total of 69 cases that were solely exposed to VPA with adequate phenotypic description were identified. The clinical manifestations of FVS encompass a wide spectrum of abnormalities including consistent facial phenotype, multiple systemic and orthopedic involvement, central nervous system dysfunction, and altered physical growth. The facial appearance is characterized by a small broad nose, small ears, flat philtrum, a long upper lip with shallow philtrum, and micro/retrognathia. In this review, 62% of the patients had musculoskeletal abnormalities, 30% had minor skin defects, 26% had cardiovascular abnormalities, 22% had genital abnormalities, and 16% had pulmonary abnormalities. Less frequently encountered abnormalities included brain, eye, kidney, and hearing defects. Neural tube defects were seen in 3% of the sample. Twelve percent of affected children died in infancy and 29% of surviving patients had developmental deficits/mental retardation. Although 15% of patients had growth retardation, an overgrowth pattern was seen in 9%. The data from this comprehensive review especially the developmental outcome should be added to the teratogenic risk, that arises in association with the use of VPA during pregnancy.

Publication types

  • Case Reports
  • Comparative Study
  • Review

MeSH terms

  • Abnormalities, Drug-Induced / etiology*
  • Abnormalities, Multiple / chemically induced*
  • Adult
  • Anticonvulsants / adverse effects*
  • Epilepsy / drug therapy
  • Face / abnormalities
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Limb Deformities, Congenital / chemically induced
  • Male
  • Neural Tube Defects / chemically induced
  • Nuclear Family
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Valproic Acid / adverse effects*

Substances

  • Anticonvulsants
  • Valproic Acid