ObjectiveGenetic diagnosis and mutation identification are now compulsory for Duchenne (DMD) and Becker muscular dystrophies (BMD), which are due to dystrophin (DMD) gene mutations, either for disease prevention or personalized therapies. To evaluate the ethnic-related genetic assortments of DMD mutations, which may impact on DMD genetic diagnosis pipelines, we studied 328 patients with DMD and BMD from non-European countries.MethodsWe performed a full DMD mutation detection in 328 patients from 10 Eastern European countries (Poland, Hungary, Lithuania, Romania, Serbia, Croatia, Bosnia, Bulgaria, Ukraine, and Russia) and 2 non-European countries (Cyprus and Algeria). We used both conventional methods (multiplex ligation-dependent probe amplification [MLPA] followed by gene-specific sequencing) and whole-exome sequencing (WES) as a pivotal study ran in 28 patients where DMD mutations were already identified by standard techniques. WES output was also interrogated for DMD gene modifiers.ResultsWe identified DMD gene mutations in 222 male patients. We identified a remarkable allele heterogeneity among different populations with a mutation landscape often country specific. We also showed that WES is effective for picking up all DMD deletions and small mutations and its adoption could allow a detection rate close to 90% of all occurring mutations. Gene modifiers haplotypes were identified with some ethnic-specific configurations.ConclusionsOur data provide unreported mutation landscapes in different countries, suggesting that ethnicity may orient genetic diagnosis flowchart, which can be adjusted depending on the mutation type frequency, with impact in drug eligibility.

Congenital cytomegalovirus infection is the most common infectious cause of congenital brain injury. Type and severity of congenital cytomegalovirus infection-related brain abnormalities depend on the developmental stage of the central nervous system at the time of fetal infection. The aim of this study was to follow the course of leukoencephalopathy in a patient with congenital cytomegalovirus infection. We describe brain magnetic resonance imaging (MRI) findings of a boy with symptomatic congenital cytomegalovirus infection performed at the age of 3 weeks, 13 months, and 4 and 7 years. Neonatal brain MRI showed most of characteristic findings in congenital cytomegalovirus infection with most prominent white matter abnormalities and cortical dysplasia. MRI follow-up images showed that cortical dysgenesis remained unchanged and static, whereas white matter abnormalities evolved over the years. We propose that leukoencephalopathy in congenital cytomegalovirus infection is not only nonprogressive or static but even evolutive and suggests both underlying disruption and delay of myelination.

<p><strong>Objective. </strong>Angioedema (AE) is a potentially life-threatening event. We investigated the etiology of AE, with the emphasis on bradykinininduced angioedema treatment in emergency medicine.</p><p><strong>Methods. </strong>The retrospective study included 237 patients with AE, who were examined and treated in two hospitals (group A and B) in Croatia from 2009 to 2016. The location and duration of AE, data about chronic diseases and treatment, potential causative agents (food, drugs, insect bites and chemicals), physical examination data and the subsequent treatment were analyzed.</p><p><strong>Results. </strong>There was no statistical difference regarding age or comorbidities but there was a statistically significant difference in etiology between the groups (Chi-square, P=0.03). Renin-angiotensin-aldosterone system (RAAS) blocker induced AE was the main cause of emergency attendance in group A (37.5%) and among the leading causes in group B (18.8%). Bradykinin-induced AE (hereditary angioedema (HAE) and RAAS-AE) were the leading causes in a total of 75 (31.5%) patients. RAAS-AE was treated with glucocorticoids and antihistamines. HAE attacks in both groups (2/7 patients, 1.5/6%) were treated with specific therapy. Other causes of AE in groups A/B were insect bites (15/23 patients, 13.5/20%), use of antibiotics/analgetics (11/17 patients, 9/15%), gastroesophageal reflux disease (10/11 patients, 8/9%), neoplasms (5/6 patients, 4/5%) and idiopatic (32/31 patients, 26.5/26%). 21% of patients were hospitalized.</p><p><strong>Conclusion. </strong>Bradykinin-mediated AE was the main cause of emergency attendance associated with AE. Advances in the treatment of HAE, with case reports of patients with RAAS-AE treated with C1 esterase inhibitor concentrate or bradykinin receptor antagonist, may prove to be a new, reliable and efficacious therapy option.</p>

Background: This cross-sectional study assessed both family and individual quality of life (QOL), and their association with self-esteem, optimism, chronic psychological stress, anxiety, and depression in parents of children with chronic conditions. Methods: Parents of children with Down syndrome (DS), autistic spectrum disorder (ASD), cerebral palsy (CP), diabetes mellitus type 1 (DMT1), and parents of children without chronic diseases with typical development (TD) were included. Multivariate linear regression analysis was used to assess parental characteristics associated with the domains of individual and family QOL. Results: Compared to the parents of TD children, parents of children with ASD and DS were more likely to report reduced family QOL in all domains, while parents of children with DMT1 had lower parental perception. Self-esteem was positively associated with all domains of individual QOL, while optimism was associated with the overall individual QOL perception and health. Higher stress perception was negatively associated with most of the domains of individual and family QOL. Conclusions: This study confirmed that parents of children with chronic conditions are more likely to have lower perception of both individual and family QOL, which were associated with self-esteem, chronic stress, anxiety, and depression. Interventions should focus not only on the child with a chronic condition but on parents too.

The aim of this population-based study was to evaluate the characteristics of cerebral palsy (CP) in relation to the predominant pattern of the magnetic resonance imaging Classification System (mriCS) that was analogously applied to the neonatal/early infant cranial ultrasound (CuS). The study included children born during the 2004-2007 period from the Croatian part (C28 rCP-hr) of the Surveillance of Cerebral Palsy in europe (SCPe) CP register. motor functions, accompanying impairments and brain mri were evaluated in 227 children, 185 of which also had CuS. Concerning CP types, 56% of children had bilateral spastic, 34% unilateral spastic, 9% dyskinetic and 1% ataxic CP type. gross motor function Classification System (gmfCS) revealed that 62.05% had mild (gmfCS i-iii) and 37.85% had severe motor impairment (gmfCS iv-v). CuS showed white matter injury in 60%, gray matter injury in 12%, maldevelopments in 8%, miscellaneous changes in 14%, while 6% were normal; mri showed significant agreement (κ=0.675, p<0.001). neuroimaging findings of maldevelopments and predominant gray matter injury were associated with more severe CP, but 7% of children with CP had normal mri. As we found very good agreement between CuS and mri findings, CuS is recommended in children at an increased risk of CP if mri is not available.