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We describe a cohort of 10 unrelated Greek patients (4 females, 6 males; median age 6.5 years, range 2–18 years) with heterogeneous epilepsy syndromes with a genetic basis. In these patients, causative genetic variants, including two novel ones, were identified in 9 known epilepsy-related genes through whole exome sequencing. A patient with glycine encephalopathy was a compound heterozygote for the p.Arg222Cys and the p.Ser77Leu AMT variant. A patient affected with Lafora disease carried the homozygous p.Arg171His EPM2A variant. A de novo heterozygous variant in the GABRG2 gene (p.Pro282Thr) was found in one patient and a pathogenic variant in the GRIN2B gene (p.Gly820Val) in another patient. Infantile-onset lactic acidosis with seizures was associated with the p.Arg446Ter PDHX gene variant in one patient. In two additional epilepsy patients, the p.Ala1662Val and the novel non-sense p.Phe1330Ter SCN1A gene variants were found. Finally, in 3 patients we observed a novel heterozygous missense variant in SCN2A (p.Ala1874Thr), a heterozygous splice site variant in SLC2A1 (c.517-2A>G), as a cause of Glut1 deficiency syndrome, and a pathogenic variant in STXBP1 (p.Arg292Leu), respectively. In half of our cases (patients with variants in the GRIN2B, SCN1A, SCN2A and SLC2A1 genes), a genetic cause with potential management implications was identified.

Introduction: Dementia severely affects the quality of life of patients and their caregivers; however, it is often not adequately addressed in the context of a primary care consultation, especially in patients with multi-morbidity.Study Population and Methods: A cross-sectional study was conducted between March-2013 and December-2014 among 3,140 consecutive patients aged >60 years visiting 14 primary health care practices in Crete, Greece. The Mini-Mental-State-Examination [MMSE] was used to measure cognitive status using the conventional 24-point cut-off. Participants who scored low on MMSE were matched with a group of elders scoring >24 points, according to age and education; both groups underwent comprehensive neuropsychiatric and neuropsychological assessment. For the diagnosis of dementia and Mild-Cognitive-Impairment (MCI), the Diagnostic and Statistical Manual-of-Mental-Disorders (DSM-IV) criteria and the International-Working-Group (IWG) criteria were used. Chronic conditions were categorized according to ICD-10 categories. Logistic regression was used to provide associations between chronic illnesses and cognitive impairment according to MMSE scores. Generalized Linear Model Lasso Regularization was used for feature selection in MMSE items. A two-layer artificial neural network model was used to classify participants as impaired (dementia/MCI) vs. non-impaired.Results: In the total sample of 3,140 participants (42.1% men; mean age 73.7 SD = 7.8 years), low MMSE scores were identified in 645 (20.5%) participants. Among participants with low MMSE scores 344 (54.1%) underwent comprehensive neuropsychiatric evaluation and 185 (53.8%) were diagnosed with Mild-Cognitive-Impairment (MCI) and 118 (34.3%) with dementia. Mental and behavioral disorders (F00-F99) and diseases of the nervous system (G00-G99) increased the odds of low MMSE scores in both genders. Generalized linear model lasso regularization indicated that 7/30 MMSE questions contributed the most to the classification of patients as impaired (dementia/MCI) vs. non-impaired with a combined accuracy of 82.0%. These MMSE items were questions 5, 13, 19, 20, 22, 23, and 26 of the Greek version of MMSE assessing orientation in time, repetition, calculation, registration, and visuo-constructive ability.Conclusions: Our study identified certain chronic illness-complexes that were associated with low MMSE scores within the context of primary care consultation. Also, our analysis indicated that seven MMSE items provide strong evidence for the presence of dementia or MCI.

Inherited muscle disorders are caused by pathogenic changes in numerous genes. Herein, we aimed to investigate the etiology of muscle disease in 24 consecutive Greek patients with myopathy suspected to be genetic in origin, based on clinical presentation and laboratory and electrophysiological findings and absence of known acquired causes of myopathy. Of these, 16 patients (8 females, median 24 years-old, range 7 to 67 years-old) were diagnosed by Whole Exome Sequencing as suffering from a specific type of inherited muscle disorder. Specifically, we have identified causative variants in 6 limb-girdle muscular dystrophy genes (6 patients; ANO5, CAPN3, DYSF, ISPD, LAMA2, SGCA), 3 metabolic myopathy genes (4 patients; CPT2, ETFDH, GAA), 1 congenital myotonia gene (1 patient; CLCN1), 1 mitochondrial myopathy gene (1 patient; MT-TE) and 3 other myopathy-associated genes (4 patients; CAV3, LMNA, MYOT). In 6 additional family members affected by myopathy, we reached genetic diagnosis following identification of a causative variant in an index patient. In our patients, genetic diagnosis ended a lengthy diagnostic process and, in the case of Multiple acyl-CoA dehydrogenase deficiency and Pompe’s disease, it enabled specific treatment to be initiated. These results further expand the genotypic and phenotypic spectrum of inherited myopathies., Highlights • 24 consecutive patients with myopathy were investigated via WES. • 16 patients and 6 family members with causative variants in 14 different genes • Causative variants in 6 LGMD genes (ANO5, CAPN3, DYSF, ISPD, LAMA2, SGCA) • Other genes involved were CPT2, ETFDH, GAA, CLCN1, LMNA, MT-TE, MYOT, CAV3. • These results expand the genotypic and phenotypic spectrum of inherited myopathies.