Valproate embryopathy: clinical and cognitive profile in 5 siblings.
Valproate embryopathy is a well recognized syndrome caused by prenatal exposure to the anticonvulsant valproic acid (Depakote). We report five half-siblings with the same mother (four different fathers) who all have valproate embryopathy. Valproic acid was the sole anticonvulsant in all five pregnancies, with doses ranging from 500 to 2,000 mg per day. All children were examined by a clinical geneticist and developmental pediatrician, and had formal developmental testing. Mean birth weight at term was 2,900 g (range: 2,400-3,400 g). Common features in the five children included: flat, broad nasal bridge (5/5), hypoplastic midface (4/5), apparent hypertelorism/telecanthus (4/5), smooth philtrum (4/5), thin upper lip (5/5), long thin tapering fingers (4/5), hypoplastic 5th toenails (2/5), and irregularly placed toes (2/5). Less frequent features were micro/brachycephaly (2/5), cleft palate (1/5), duplication cyst of small intestine (1/5), and hemangioma (1/5). None had neural tube defect. Neuropsychologic testing of the three children older than 4 years of age showed cognitive ability in the low normal or borderline range (mean IQ = 83; range: 75-86), with significantly lower scores in adaptive behavior and motor skills. Study of this family offers insight into the potentially high risk of valproate embryopathy in exposed pregnancies, and affords a unique opportunity to study the variability of expression and cognitive profile of the syndrome within one family.
Schorry
Elizabeth K
EK
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. Elizabeth.Schorry@cchmc.org
Oppenheimer
Sonya G
SG
Saal
Howard M
HM
D000014:Abnormalities, Drug-Induced / Q000473:pathology* / Q000523:psychology; D000015:Abnormalities, Multiple / Q000139:chemically induced / Q000473:pathology* / Q000523:psychology; D000927:Anticonvulsants / Q000009:adverse effects; D002648:Child; D002652:Child Behavior / Q000187:drug effects; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects; D002658:Developmental Disabilities / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009483:Neuropsychological Tests; D035781:Siblings; D013577:Syndrome; D014635:Valproic Acid / Q000009:adverse effects*
D000927:Anticonvulsants; D014635:Valproic Acid