Valproic acid embryopathy: report of two siblings with further expansion of the phenotypic abnormalities and a review of the literature.
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.
Kozma
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Child Development Center/Department of Pediatrics, Georgetown University Medical Center, Washington, DC 20007-3935, USA. kozmac@gunet.georgetown.edu
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000015:Abnormalities, Multiple / Q000139:chemically induced*; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D004827:Epilepsy / Q000188:drug therapy; D005145:Face / Q000002:abnormalities; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017880:Limb Deformities, Congenital / Q000139:chemically induced; D008297:Male; D009436:Neural Tube Defects / Q000139:chemically induced; D009679:Nuclear Family; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D014635:Valproic Acid / Q000009:adverse effects*
D000927:Anticonvulsants; D014635:Valproic Acid