Abstracts

RATIONALE: Certain mutations in the fibroblast growth factor receptor 3 (FGFR3) gene result in dwarfing disorders (achondroplasia and hypochondroplasia), which are associated with intracranial features including macrocephaly, ventriculomegaly and hydrocephalus. FGFR3 is expressed in cartilage and also in brain. Thus, mutations might be expected to be associated with functional abnormalities in the brain. Subjectively it was our impression that seizures might be unusually common in these populations but seizure frequency has not been well defined. METHODS: Records of a population of 173 patients with FGFR3 mutation associated disorders followed at the Midwest Regional Bone Dysplasia Clinic were retrospectively reviewed to identify all individuals with seizures and to characterize seizure type and frequency, treatment modalities, etiologic and precipitating factors, EEG and imaging findings. RESULTS: Of the 173 subjects, 9 (5.2%) had seizures (8/155 achondroplasia and 1/18 hupochondroplasia). Onset was from birth to age 20 years. Six had seizures in the first year of life, presenting as apnea (5/6) and tonic-clonic seizures (1/6). In those presenting with apnea hypomotor seizures (3/5), tonic-clonic seizures(1/5) and subtle convulsive status-epilepticus (1/5) were associated. Outside infancy, 2 had complex partial seizures (age 2, 20), and one had generalized tonic-clonic seizures (age 4). Focal epileptiform discharges were present in EEG studies of 7/9 individuals. Neuroimaging showed no abnormality in 2, benign ventriculomegaly in 3, hydrocephalus in 2 and multicystic encephalomalacia in one. Therapy included short term (<6 mo) phenobarbital(2), chronic (>6 mo) phenobarbital (1), short term phenytoin (2) and chronic carbamezapine (3); one patient was not treated. CONCLUSIONS: The incidence of seizures in those with FGFR3 mutations appears to be about 5 times that of the general population. Most often, seizures begin in the first year of life. Apnea (especially daytime) in these populations may often be seizure precipitated. Slighly less than half of thise with documented seizures required long term anti-seizure therapy.