Abstracts

EFMR (Epilepsy and Mental Retardation limited to Females) is a rare disorder with a remarkable X-linked inheritance pattern with male sparing. A single large family has been previously described with the disease gene mapping to Xq22. EFMR is characterised by seizures beginning early in life, with developmental regression following seizure onset. Affected females have variable degrees of intellectual disability (ID). We describe 3 new families with EFMR where mapping is consistent with the Xq22 locus. We ascertained 3 unrelated families where seizures in females were transmitted through unaffected males; two from Australia and one from Israel. Detailed electroclinical assessment was performed on 37 individuals. The segregation of Xq22 markers with the disease locus was examined. Onset of seizures was at a mean of 11 months (median 11, range 3-36). Affected girls typically presented with GTCS, often associated with fever. Some individuals had partial, absence, atonic and myoclonic seizures. Seizures often ceased by the second decade. Developmental regression occurred in 14 females, typically with seizure onset. Intellect ranged from normal to severe ID. Autistic features were prominent in one family, and one woman had schizophrenia. Brain imaging studies were normal (4 CT, 1 MRI). Although each family was of insufficient size to demonstrate linkage, haplotype analyses were consistent with the Xq22 localisation. We report 3 new families with the remarkable condition of EFMR where females are affected with epilepsy and developmental regression, and carrier males are clinically unaffected. This disorder is characterized by an extraordinary pattern of inheritance where male sparing occurs and females with the same mutation show marked variability in severity. (Supported by NHMRC, Bionomics.)