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Epilepsy and Mental Retardation limited to Females (EFMR) which links to Xq22 has been reported in only one family. We aimed to determine if there was a distinctive phenotype that would enhance recognition of this disorder. We ascertained four unrelated families (two Australian, two Israeli) where seizures in females were transmitted through carrier males. Detailed clinical assessment was performed on 58 individuals, using a validated seizure questionnaire, neurological examination and review of EEG and imaging studies. Gene localization was examined using Xq22 microsatellite markers. Twenty-seven affected females had a mean seizure onset of 14 months (range 6-36) typically presenting with convulsions. All had convulsive attacks at some stage, associated with fever in 17 out of 27 (63%). Multiple seizure types occurred including tonic-clonic (26), tonic (4), partial (11), absence (5), atonic (3) and myoclonic (4). Seizures ceased at mean 12 years. Developmental progress varied from normal (7), to always delayed (4) to normal followed by regression (12). Intellect ranged from normal to severe intellectual disability (ID), with 67% of females having ID or being of borderline intellect. Autistic (6), obsessive (9) and aggressive (7) features were prominent. EEGs showed generalized and focal epileptiform abnormalities. Five obligate male carriers had obsessional tendencies. Linkage to Xq22 was confirmed (maximum lod 3.5 at [theta] = 0). We conclude that EFMR is a distinctive, under-recognized familial syndrome where girls present with convulsions in infancy, often associated with intellectual impairment and autistic features. The unique inheritance pattern with transmission by males is perplexing. Clinical recognition is straightforward in multiplex families due to the unique inheritance pattern; however, this disorder should be considered in smaller families where females alone have seizures beginning in infancy, particularly in the setting of developmental delay. In single cases, diagnosis will depend on identification of the molecular basis.

To estimate the prevalence of essential tremor (ET) in Arabic villages of Wadi Ara. The prevalence ET which is higher than Parkinson’s disease in North America and Europe, differs according to study population and methodology. Since hospital record based epidemiology carries referral bias and might provide low estimates of ET prevalence, we carried a population based survey. This door-to-door survey comprised the Arabic villages of Wadi Ara in Northern Israel. Consecutive residents who agreed to participate in the study and were older than 64 years at prevalence day, underwent neurological examination. Medical and family history, medication and response to medication were recorded. Of the 444 subjects that were approached, 428 agreed to participate in the study (refusal rate 3.6%). Four were excluded owing to severe systemic disease. The study population consisted of 424 subjects (54% men, mean age 74 ± 7 years). A clearly oscillatory action tremor of moderate amplitude was observed in 8 patients (age 75 ± 7 years). Six patients had another possible cause of tremor. The prevalence of ET was calculated as 1.89% (95% CI 1.76–2.0) when all tremor cases were accepted as possible ET and 0.47% (95 CI 0.43–0.52) when patients with other causes of tremor were excluded. The prevalence of ET in Arabic villages of Wadi Ara is low. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis., Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate., Results: A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A, KCNQ2, CSTB), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1, PCDH19, TBC1D24). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically., Conclusion: A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies., (© 2016 American Academy of Neurology.)

Background: The Mini-mental State Examination (MMSE) has not been validated in Arabic speaking populations. The Brookdale Cognitive Screening Test (BCST) has been developed for use in low schooling populations. We investigated the influence of gender, education and occupation in a cognitively normal community sample which was assessed using an Arabic translation of the MMSE and the BCST., Methods: Cognitively normal subjects (n=266, 59.4% males, mean age (SD): 72.4 (5.5) years) from an Arab community in northern Israel (Wadi Ara) were evaluated. Education was categorized into levels: 1=0-4 years, 2=5-8 years, 3=9-12 years. Effects of gender, education and occupation on MMSE and BCST were analyzed by ANOVA, taking age as a covariate., Results: The mean MMSE score of males [26.3 (4.1)] was higher than that of females [23.6 (4.2) points]. Two-way ANOVA showed a significant interaction between gender and education on MMSE (p=0.0017) and BCST scores (p=0.0002). The effect of gender on MMSE and BCST was significant in education level 1 (p<0.0001, both tests) and level 2 (p<0.05, both tests). For education level 1, MMSE and BCST scores were higher for males, while both scores were higher for females in education level 2. The effect of occupation was not significant for both genders., Conclusion: Education and gender influence performance when using the Arabic translation of the MMSE and BCST in cognitively normal elderly. Cognitively normal females with 0-4 years of education scored lower than males. These results should be taken into consideration in the daily use of these instruments in Arabic.