Clusters of cognitive impairment among different phenotypes of myotonic dystrophy type 1 and type 2

Neuropsychological examinations in myotonic dystrophy (DM) patients show a great variability of results from a condition of intellectual disability to the subtle cognitive impairments. It is unclear if different clusters of neuropsychological deficits appear in different phenotypes of DM, or if there are patients with no cognitive deficit at all. The aim of this study is to assess cognitive impairments among patients with different phenotypes of DM type 1 (DM1) and type 2 (DM2), and to potentially define cognitive clusters in these disorders. Study comprised 101 DM1 and 46 DM2 adult patients who were genetically confirmed. Patients underwent analysis of five cognitive domains (visuospatial, executive, attention, memory and language). Virtually all DM1 patients had cognitive defect with approximately 2–3 cognitive domains affected. On the other hand, one-third of DM2 patients had completely normal neuropsychological findings, and in other two-thirds approximately 1–2 domains were affected. Cluster analysis showed that in both diseases visuospatial and executive dysfunctions seemed to be the main cognitive defects, while memory and language impairments appeared in more severe phenotypes. Our results showed that a single form of DM1 or DM2 may consist of several cognitive clusters. Understanding of cognitive impairments in DM is very important to follow positive and side effects in ongoing and future clinical trials.     

Brain sonography insight into the midbrain in myotonic dystrophy type 2

Introduction: The aim of this study was to analyze transcranial sonography (TCS) findings in genetically confirmed myotonic dystrophy type 2 (DM2) patients. Methods: Forty DM2 patients and 38 gender‐ and age‐matched healthy controls (HCs) underwent TCS through the pre‐auricular acoustic bone window. Results: Substantia nigra hyperechogenicity was found in 20% of DM2 patients compared with 3% of HCs. Brainstem raphe (BR) hypoechogenicity was more common in DM2 patients compared with HCs (56% vs. 10%, P < 0.01), and it was more common in patients with fatigue and excessive daytime sleepiness (P < 0.05). Diameter of the third ventricle was increased in DM2 patients compared with HCs (5.8 ± 1.7 vs. 5.1 ± 1.0 mm, P < 0.05). Conclusions: Finding BR hypoechogenicity might have clinical implication because of the potential response to serotonin‐reuptake inhibitors. TCS revealed alterations in brain structures previously not seen in MRI studies. Muscle Nerve 53 : 700–704, 2016     

Nonterrorist suicides using hand grenades on the territory of the Autonomous Province of Vojvodina, Serbia, from 1990 to 2009

Suicides using hand grenades are very rare. The aim of this retrospective study was to evaluate the cases of nonterrorist suicides using hand grenades according to the number of cases per year, sex, age categories, season of the year, day of the week, ethanol blood level, type of hand grenade, pattern of injuries, risk factors, and suicide place over a 20-year period, from 1990 to 2009 in Vojvodina, Serbia. The total number of the cases in this period was 81, with the highest number of cases in 1997 and 2002. Twelwe victims were part of six double suicides, where one grenade was used to commit suicide to both victims. The results highlighted male predominance of the victims, sober state, the use of military hand grenades (M75 and M52 type), posttraumatic stress disorder due to participation in military clashes as the main risk factor, and countryside as the place of suicide.     

A novel keratin 5 mutation (K5V186L) in a family with EBS-K: a conservative substitution can lead to development of different disease phenotypes.

Epidermolysis bullosa simplex is a hereditary skin blistering disorder caused by mutations in the KRT5 or KRT14 genes. More than 50 different mutations have been described so far. These, and reports of other keratin gene mutations, have highlighted the existence of mutation "hotspots" in keratin proteins at which sequence changes are most likely to be detrimental to protein function. Pathogenic mutations that occur outside these hotspots are usually associated with less severe disease phenotypes. We describe a novel K5 mutation (V186L) that produces a conservative amino acid change (valine to leucine) at position 18 of the 1A helix. The phenotype of this case is unexpectedly severe for the location of the mutation, which lies outside the consensus helix initiation motif mutation hotspot, and other mutations at this position have been associated in Weber--Cockayne (mild) epidermolysis bullosa simplex only. The mutation was confirmed by mismatch-allele-specific polymerase chain reaction and the entire KRT5 coding region was sequenced, but no other changes were identified. De novo K5/K14 (mutant and wild-type) filament assembly in cultured cells was studied to determine the effect of this mutation on filament polymerization and stability. A computer model of the 1A region of the K5/K14 coiled-coil was generated to visualize the structural impact of this mutation and to compare it with an analogous mutation causing mild disease. The results show a high level of concordance between genetic, cell culture and molecular modeling data, suggesting that even a conservative substitution can cause severe dysfunction in a structural protein, depending on the size and structure of the amino acid involved.     

Metabolic syndrome in patients with myotonic dystrophy type 1

Introduction: The aim of this study was to assess the frequency and features of metabolic syndrome (MetS) in myotonic dystrophy type 1 (DM1). Methods: We studied 66 DM1 patients (50% men, aged 41.9 ± 10.5 years, disease duration of 19.3 ± 8.6 years). New worldwide consensus criteria for MetS from 2009 were used. Results: Components of MetS were present at the following frequencies: hypertriglyceridemia 67%; low HDL cholesterol 35%; hypertension 18%; central obesity 14%; and hyperglycemia 9%. MetS was present in 11 (17%) patients. The presence of MetS was not associated with patients' gender, age, disease severity, disease duration, or CTG repeat length (P > 0.05). Patients with MetS had significantly lower total SF‐36 scores as a measure of quality of life in comparison to patients without MetS (P < 0.05). Conclusion: Although certain components of MetS were very frequent in patients with DM1, only 17% met the criteria for MetS. Muscle Nerve 52 : 273–277, 2015