Autosomal recessive cortical myoclonic tremor and epilepsy: association with a mutation in the potassium channel associated gene CNTN2.

We characterize a consanguineous Egyptian family with an autosomal recessively inherited familial cortical myoclonic tremor and epilepsy. We used multipoint linkage analysis to map the causative mutation to a 12.7 megabase interval within 1q31.3-q32.2 with a log of odds score of 3.6. For further investigation of the linked region in an efficient and unbiased manner, we performed exome sequencing. Within the suspected region we identified a homozygous single base pair deletion (c.503_503delG) leading to a frameshift in the coding region of the sixth exon of CNTN2 alias TAG-1 (p.Trp168fs), which segregated in the respective family. Many studies point towards an important role of the CNTN2 product contactin 2 in neuronal excitability. Contactin 2, a glycosylphosphatidylinositol-anchored neuronal membrane protein, and another transmembrane protein called contactin associated protein-like 2 (CNTNAP2 alias CASPR2) are together necessary to maintain voltage-gated potassium channels at the juxtaparanodal region. CNTN2 knockout mice were previously reported to suffer from spontaneous seizures and mutations in the CNTNAP2 gene have been described to cause epilepsy in humans. To further delineate the role of CNTN2 in patients with epilepsy, we sequenced the coding exons in 189 Caucasian patients with epilepsy. No recessive mutation was detected and heterozygote carriers of rare CNTN2 variants do not seem to be predisposed to epilepsy. Given the severity of the mutation and the proposed function of the gene, we consider this mutation as the most likely cause for cortical myoclonic tremor and epilepsy in this family.

Consensus Guideline on the Management of Epilepsy in Egypt: A National Delphi Consensus Study.

OBJECTIVE: In epilepsy, early diagnosis, accurate determination of epilepsy type, proper selection of antiseizure medication, and monitoring are all essential. However, despite recent therapeutic advances and conceptual reconsiderations in the classification and management of epilepsy, serious gaps are still encountered in day-to-day practice in Egypt as well as several other resource-limited countries. Premature mortality, poor quality of life, socio-economic burden, cognitive problems, poor treatment outcomes, and comorbidities are major challenges that require urgent actions to be implemented at all levels. In recognition of this, a group of Egyptian epilepsy experts met through a series of consecutive meetings to specify the main concepts concerning the diagnosis and management of epilepsy, with the ultimate goal of establishing a nationwide Egyptian consensus. METHODS: The consensus was developed through a modified Delphi methodology. A thorough review of the most recent relevant literature and international guidelines was performed to evaluate their applicability to the Egyptian situation. Afterward, several remote and live rounds were scheduled to reach a final agreement for all listed statements. RESULTS: Of 278 statements reviewed in the first round, 256 achieved ≥80% agreement. Live discussion and refinement of the 22 statements that did not reach consensus during the first round took place, followed by final live voting then consensus was achieved for all remaining statements. SIGNIFICANCE: With the implementation of these unified recommendations, we believe this will bring about substantial improvements in both the quality of care and treatment outcomes for persons with epilepsy in Egypt. PLAIN LANGUAGE SUMMARY: This work represents the efforts of a group of medical experts to reach an agreement on the best medical practice related to people with epilepsy based on previously published recommendations while taking into consideration applicable options in resource-limited countries. The publication of this document is expected to minimize many malpractice issues and pave the way for better healthcare services on both individual and governmental levels.