Fetal valproate phenotype is recognisable by mid pregnancy.

Serville, F; Carles, Dominiques; Guibaud, S; Dallay, D.

doi:10.1136/jmg.26.5.348

“…In an effort to further delineate the phenotypic features of FVS, the English literature was reviewed from 1978-2000 to identify patients with FVS. Cases that did not have adequate phenotypic description were excluded [Stanley and Chambers, 1982;Oakeshott and Hunt, 1989;Lindhout et al, 1992;Hockey et al, 1996; Case 3] as well as cases that were exposed to VPA and other anticonvulsant treatment [Thomas and Buchanan, 1981;Gomez, 1981;DiLiberti et al, 1984 Cases 2,4,5;Chitayat et al, 1988 Cases 1,2;Ardinger et al, 1988 Cases 9-19;Serville et al, 1989Christianson et al, 1994Thisted and Ebbesen, 1993 Cases 12-17;Baggot et al, 1999].…”

Section: Discussionmentioning

confidence: 99%

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

Kozma

¹

2001

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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.

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“…In an effort to further delineate the phenotypic features of FVS, the English literature was reviewed from 1978–2000 to identify patients with FVS. Cases that did not have adequate phenotypic description were excluded [Stanley and Chambers, 1982; Oakeshott and Hunt, 1989; Lindhout et al, 1992; Omtzigt et al, 1992; Hockey et al, 1996; Case 3] as well as cases that were exposed to VPA and other anticonvulsant treatment [Thomas and Buchanan, 1981; Gomez, 1981; DiLiberti et al, 1984 Cases 2,4,5; Chitayat et al, 1988 Cases 1,2; Ardinger et al, 1988 Cases 9–19; Serville et al, 1989 Christianson et al, 1994 Cases 1,2; Thisted and Ebbesen, 1993 Cases 12–17; Baggot et al, 1999].…”

Section: Discussionmentioning

confidence: 99%

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

Kozma

2001

View full text Add to dashboard Cite

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.

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“…Ardinger et al (1988) verified and confirmed DiLiberti et d ' s (1984) description of FVS in 19 children prenatally exposed to VPA. The syndrome becomes apparent as early as at midgestation stage of development (Serville et al, 1989). Robert and Guibaud (1982) and their colleagues interviewed 146 mothers of infants with spina bifida in the Rhone-Alps region of France and observed an unusual number of them were epileptic and had used VPA during pregnancy.…”

Section: Human Studiesmentioning

confidence: 99%

Valproic acid‐induced congenital malformations: Clinical and experimental observations

Padmanabhan

¹

,

Abdulrazzaq

²

,

Bastaki

³

2000

Congenital Anomalies

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With a large number of epileptic women being in the childbearing age group, complications of pregnancy in epileptic patients are of concern. Epileptic women are treated with antiepileptic drugs (AED) whether they are pregnant or not. Contrary to prevailing opinion, recent data suggest that epilepsy per se contributes significantly to birth defects possibly because of the same genetic susceptibility that predisposes to epilepsy. Many of these defects closely resemble those attributed to exposure to AED. The syndromes attributed to various AED also considerably overlap with each other. Valproic acid (VPA) induces several minor and major malformations. The relative risk for spina bifida in VPA exposed pregnancies is nearly 20 times higher than that for the general population and about 10 times higher than that attributed to other anticonvulsants. Fetuses of experimental animals treated with VPA during pregnancy exhibit exencephaly unlike the human offspring in whom VPA induces spina bifida. The cranial and spinal malformations observed in humans and laboratory animals indicate that VPA has a preferentially deleterious effect on the neural crest. Several AEDs including VPA tend to lower maternal plasma folate levels. In view of the beneficial effects of periconceptional folate supplementation in prevention of neural tube defects (NTD), future research should be directed at the role of folate in the possible alleviation of VPA‐induced NTD. It is also necessary to continue prospective studies to monitor the old and new AED prescribed and to evaluate the role of interactions between drugs used in combinations.

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Fetal valproate phenotype is recognisable by mid pregnancy.

Cited by 7 publications

References 3 publications

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

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

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

Valproic acid‐induced congenital malformations: Clinical and experimental observations

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