Fetal anticonvulsant syndrome and mutation in the maternal MTHFR gene

J C S Dean, S J Moore, A Osborne, J Howe, P D Turnpenny

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Around 6% of infants born to mothers taking anticonvulsants have malformations, including neural tube defects, and a further proportion show developmental delay in later childhood. Three commonly used anticonvulsants, carbamazepine, phenytoin and sodium valproate, interfere with folic acid metabolism. We investigated the common 677 C > T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in samples from 57 patients and their parents and 152 controls to determine its contribution to the risk of fetal anticonvulsant syndrome. The 677 C > T mutation frequency was significantly higher in the mothers than in the controls, but there was no significant difference in 677 C > T frequency in the patients or in the fathers. Genotype frequencies in the mothers were significantly different from controls, there being an excess of 677 C > T homozygotes. Amongst the patients, there was an apparent excess of heterozygotes (not statistically significant), and the fathers were not significantly different from controls. Mutation in the MTHFR gene in a mother taking sodium valproate, phenytoin or carbamazepine during pregnancy is associated with fetal anticonvulsant syndrome in her offspring. The skewed distribution of genotypes in the affected children probably reflects the association of fetal anticonvulsant syndrome with the maternal genotype.

Original languageEnglish
Pages (from-to)216-220
Number of pages5
JournalClinical Genetics
Volume56
Publication statusPublished - 1999

Keywords

  • anticonvulsants
  • developmental delay
  • folic acid
  • malformations
  • MTHFR mutation
  • NEURAL-TUBE DEFECTS
  • RISK FACTOR
  • METHYLENETETRAHYDROFOLATE REDUCTASE
  • VALPROATE SYNDROME
  • COMMON MUTATION
  • SPINA-BIFIDA
  • CARBAMAZEPINE
  • FOLATE
  • PREGNANCY
  • EPILEPSY

Cite this

Dean, J. C. S., Moore, S. J., Osborne, A., Howe, J., & Turnpenny, P. D. (1999). Fetal anticonvulsant syndrome and mutation in the maternal MTHFR gene. Clinical Genetics, 56, 216-220.

Fetal anticonvulsant syndrome and mutation in the maternal MTHFR gene. / Dean, J C S ; Moore, S J ; Osborne, A ; Howe, J ; Turnpenny, P D .

In: Clinical Genetics, Vol. 56, 1999, p. 216-220.

Research output: Contribution to journalArticle

Dean, JCS, Moore, SJ, Osborne, A, Howe, J & Turnpenny, PD 1999, 'Fetal anticonvulsant syndrome and mutation in the maternal MTHFR gene' Clinical Genetics, vol. 56, pp. 216-220.
Dean JCS, Moore SJ, Osborne A, Howe J, Turnpenny PD. Fetal anticonvulsant syndrome and mutation in the maternal MTHFR gene. Clinical Genetics. 1999;56:216-220.
Dean, J C S ; Moore, S J ; Osborne, A ; Howe, J ; Turnpenny, P D . / Fetal anticonvulsant syndrome and mutation in the maternal MTHFR gene. In: Clinical Genetics. 1999 ; Vol. 56. pp. 216-220.
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AU - Howe, J

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AB - Around 6% of infants born to mothers taking anticonvulsants have malformations, including neural tube defects, and a further proportion show developmental delay in later childhood. Three commonly used anticonvulsants, carbamazepine, phenytoin and sodium valproate, interfere with folic acid metabolism. We investigated the common 677 C > T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in samples from 57 patients and their parents and 152 controls to determine its contribution to the risk of fetal anticonvulsant syndrome. The 677 C > T mutation frequency was significantly higher in the mothers than in the controls, but there was no significant difference in 677 C > T frequency in the patients or in the fathers. Genotype frequencies in the mothers were significantly different from controls, there being an excess of 677 C > T homozygotes. Amongst the patients, there was an apparent excess of heterozygotes (not statistically significant), and the fathers were not significantly different from controls. Mutation in the MTHFR gene in a mother taking sodium valproate, phenytoin or carbamazepine during pregnancy is associated with fetal anticonvulsant syndrome in her offspring. The skewed distribution of genotypes in the affected children probably reflects the association of fetal anticonvulsant syndrome with the maternal genotype.

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KW - developmental delay

KW - folic acid

KW - malformations

KW - MTHFR mutation

KW - NEURAL-TUBE DEFECTS

KW - RISK FACTOR

KW - METHYLENETETRAHYDROFOLATE REDUCTASE

KW - VALPROATE SYNDROME

KW - COMMON MUTATION

KW - SPINA-BIFIDA

KW - CARBAMAZEPINE

KW - FOLATE

KW - PREGNANCY

KW - EPILEPSY

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VL - 56

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JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

ER -