• Clinical and Experimental Pediatrics
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• v.45 no.10
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• pp.1288-1291
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• 2002

Fetal valproate syndrome has been described as a distinctive pattern of minor anomalies of the face and digits. This pattern has not been delineated completely but appears to involve brachycephaly with a high forehead, shallow orbit, ocular hypertelorism, small nose, small mouth, low set posteriorly rotated ears, long overlapping fingers and toes, and hyperconvex fingernail. Cleft palate and congenital heart disease have occasionally been described in babies exposed to valproate during embryogenesis. We report a neonate born from an epileptic mother receiving sodium valproate during pregnancy. This neonate presented with characteristic facial abnormalities, both elbow contractures, and overlapping of right first and second toe, forth and fifth toe, and left first and second toe. This case raises the possibility that these abnormal appearances might be caused by intrauterine valproate exposure.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.389-396
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• 2020

Valproic acid is a clinically used mood stabilizer and antiepileptic drug. Valproic acid has been suggested as a teratogen associated with the manifestation of neurodevelopmental disorders, such as fetal valproate syndrome and autism spectrum disorders, when taken during specific time window of pregnancy. Previous studies proposed that prenatal exposure to valproic acid induces abnormal proliferation and differentiation of neural progenitor cells, presumably by inhibiting histone deacetylase and releasing the condensed chromatin structure. Here, we found valproic acid up-regulates the transcription of T-type calcium channels by inhibiting histone deacetylase in neural progenitor cells. The pharmacological blockade of T-type calcium channels prevented the increased proliferation of neural progenitor cells induced by valproic acid. Differentiated neural cells from neural progenitor cells treated with valproic acid displayed increased levels of calcium influx in response to potassium chloride-induced depolarization. These results suggest that prenatal exposure to valproic acid up-regulates T-type calcium channels, which may contribute to increased proliferation of neural progenitor cells by inducing an abnormal calcium response and underlie the pathogenesis of neurodevelopmental disorders.