topiramate and Abnormalities--Multiple

2q23.1 microdeletion syndrome is a recently characterized chromosomal aberration disorder uncovered through array comparative genomic hybridization (array CGH). Although the cardinal feature is intellectual disability (ID), neurodevelopmental features of the syndrome have not been systematically reviewed. We present a 5-year-old boy with severe psychomotor developmental delay/ID, progressive microcephaly with brain atrophy, growth retardation, and several external anomalies. He manifested intractable epilepsy, effectively treated with combined antiepileptic drug therapy including topiramate. Array CGH demonstrated a de novo interstitial deletion of approximately 1 Mb at 2q23.1-q23.2, involving four genes including MBD5. Nineteen patients have been reported to have the syndrome, including present patient. All patients whose data were available had ID, 17 patients (89%) had seizures, and microcephaly was evident in 9 of 18 patients (50%). Deletion sizes ranged from 200 kb to 5.5 Mb, comprising 1-15 genes. MBD5, the only gene deleted in all patients, is considered to be responsible for ID and epilepsy. Furthermore, the deletion junction was sequenced for the first time in a patient with the syndrome; and homology of three nucleotides, identified at the distal and proximal breakpoints, suggested that the deletion might have been mediated by recently-delineated genomic rearrangement mechanism Fork Stalling and Template Switching (FoSTeS)/microhomology-mediated break-induced replication (MMBIR).

Topics: Abnormalities, Multiple; Child, Preschool; Chromosomes, Human, Pair 2; Comparative Genomic Hybridization; Developmental Disabilities; DNA-Binding Proteins; Fructose; Humans; Intellectual Disability; Male; Microcephaly; Oligonucleotide Array Sequence Analysis; Seizures; Sequence Deletion; Topiramate

We present a case of a woman who used topiramate (100 mg) and oxcarbazepine (300 mg) continuously during pregnancy. Multiple fetal anomalies including limp defects of the lower extremities, pericardiac fluid collection, cardiomegaly, cleft lip and palate, absent right kidney, and dysplastic left kidney were found by ultrasonography. Labor was induced and anomalies were confirmed by autopsy. The malformation rate after exposure to oxcarbazepine in utero as a monotherapy was calculated to be 2.4%, which is compatible with the malformation rate seen in the general population. Topiramate is teratogenic in mice, rats, and rabbits, but there are very few reports about its teratogenicity in humans.

Topics: Abnormalities, Multiple; Adult; Anticonvulsants; Carbamazepine; Female; Fetus; Fructose; Humans; Oxcarbazepine; Pregnancy; Prenatal Exposure Delayed Effects; Topiramate; Ultrasonography, Prenatal

Twenty-eight patients with concomitant cranio-vertebral anomaly: Kimmerle anomaly and Chiari type I malformation were examined. A main reason for visiting a doctor was headache, dizziness and sleep disturbance. Topamax (topiramate) was used for stopping the symptoms. It was prescribed in dosage 25 mg in the evening to 16 patients and in dosage 25 mg in the first two weeks and then in dosage 50 mg in the evening for 60 days - to 12 patients. The use of Topamax led to the reduction and /or disappearance of headache, sleep normalization and improvement of cerebral bioelectric activity. The drug was well tolerated.

Topics: Abnormalities, Multiple; Adult; Cervical Atlas; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Fructose; Headache Disorders; Humans; Male; Middle Aged; Neuroprotective Agents; Skull; Sleep; Topiramate; Treatment Outcome; Young Adult

Topiramate is a new generation, antiepileptic drug used for the treatment of persistent partial crises. To date no specific teratogenic effects have been reported in humans, but they have appeared in experimental animals. We present the case of a neonate whose mother suffered from partial epilepsy, which was treated with topiramate throughout pregnancy at doses of 300 mg per day. When the child was born agenesis of the right thumb, hypoplasia of the left thumb, and syndactylia of the second and third toes of the foot with agnesis of some phalanges, and hypoplasia of the right orbicular muscle in the mouth were observed. No etiologic cause was found. We discuss whether there could have been a causal relationship with topiramate monotherapy.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Anticonvulsants; Bone and Bones; Female; Fructose; Humans; Infant, Newborn; Male; Maternal-Fetal Exchange; Pregnancy; Topiramate