Novel intragenic deletion in OPHN1 in a family causing XLMR with cerebellar hypoplasia and distinctive facial appearance

Al‐Owain M, Kaya N, Al‐Zaidan H, Al‐Hashmi N, Al‐Bakheet A, Al‐Muhaizea M, Chedrawi A, Basran RK, Milunsky A. Novel intragenic deletion in OPHN1 in a family causing XLMR with cerebellar hypoplasia and distinctive facial appearance. X‐linked mental retardation (XLMR) is notably a heterogeneous condition and often poses a diagnostic challenge. The oligophrenin 1 gene (OPHN1) is a protein with a Rho‐GTPase‐activating domain required in the regulation of the G‐protein cycle. Mutations in the OPHN1 cause XLMR with cerebellar hypoplasia and distinctive facial appearance. We report a large Saudi family of four boys and one girl affected with XLMR. The boys had moderate MR, seizure disorder, facial dysmorphism, and cerebellar vermis hypoplasia. The girl had mild MR, seizures, and mild cerebellar hypoplasia. A novel deletion of at least exons 7–15 was identified by polymerase chain reaction analysis and multiple ligation probe amplification of the OPHN1 gene. The array comparative genomic hybridization further delineated approximately 68 kb deletion of the 7–15 exons and nearly half of intron 15. In addition, the X‐inactivation confirmed random pattern in the girl. Although the affected boys have remarkably similar phenotype, there was some variability in the severity of the seizure disorder and the cerebellar hypoplasia. The report confirms the previous findings that carrier females may be symptomatic.     

Is self-reported improvement in osteoarthritis pain and disability reflected in objective measures?

OBJECTIVE: To determine if self-reported improvements in pain and function correlate with improvement in objective measures of disease in osteoarthritis (OA). METHODS: Individuals with disabling hip/knee OA were assessed 7 years apart by questionnaire [sociodemographics, body mass index, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores] and physical [range of motion (ROM), disease activity based on joint stress pain, erythema, warmth, effusion] and radiographic examination of the hips and knees (Kellgren-Lawrence grade). Changes over time were expressed as improved, unchanged, or worse based on a priori criteria. RESULTS: Of 69 eligible patients, 43 (64%) with a mean age of 76.3 years participated; 77% were female. For WOMAC scores, 25% and 19% reported improved pain and function, respectively. For joint ROM, disease activity, and radiographic grade, 0% to 30% of participants were improved. However, improvements in WOMAC scores were not associated with improvements in any of the other measures (r < 0.24 for all). CONCLUSION: One-quarter of participants reported significant improvements in WOMAC pain and disability after 7 years' followup. However, these improvements were not associated with similar improvements in joint ROM, disease activity, or radiographic grade. Greater understanding of the determinants of self-reported improvements in arthritis status, in particular the role of adaptation, is warranted.     

Parent and teacher perceptions of child behaviour following cardiac surgery

To determine if parents whose children had undergone successful cardiac surgery perceived their children any differently from parents of children who had not undergone surgery, we used the Achenbach Child Behaviour Checklist (CBCL) to compare parent and teacher perceptions in these two groups. Subjects included 168 children who had undergone cardiac surgery 4 to 8 years previously and 51 controls. On the behaviour scale of the CBCL, the teachers' mean t scores showed no significant difference bctween the cardiac and control groups, in contrast to the parents' scores where parents perceived a higher degree of behavioural problems in children who had undergone cardiac surgery. On the Social competence scale of the CBCL, the parents scored their children who had undergone cardiac surgery as less Socially competent than did the parents of the controls. Teachers' scores showed no difference between groups.     

Validation of the parent-proxy pediatric Charcot-Marie-Tooth disease quality of life outcome measure

Charcot-Marie-Tooth disease (CMT) reduces health-related quality of life (QOL) in children. We have previously developed and validated the English and Italian versions of the pediatric CMT-specific QOL outcome measure (pCMT-QOL) for children aged 8 to 18. There is currently no parent-proxy CMT QOL outcome measure for use in clinical trials, which could provide complementary information in these children and adolescents. This study describes the validation studies conducted to develop the parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 years old. Development and validation of the parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 years old was iterative, involving identifying relevant domains, item pool generation, prospective pilot testing and clinical assessments, structured focus-group interviews, and psychometric testing, conducted on parents of children with CMT seen at participating sites from the USA, United Kingdom, and Australia. We utilized previously described methods to develop a working parent-proxy version of the pCMT-QOL measure. From 2010 to 2016, the parent-proxy pCMT-QOL working version was administered to 358 parents of children with CMT aged 8 to 18, seen at the participating study sites of the Inherited Neuropathies Consortium. The resulting data underwent rigorous psychometric analysis, including factor analysis, test-retest reliability, internal consistency, convergent validity, IRT analysis, and longitudinal analysis, to develop the final parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 years old. The parent-proxy version of the pCMT-QOL outcome measure is a reliable, valid, and sensitive proxy measure of health-related QOL for children aged 8 to 18 with CMT.     

Anterior tibialis cmap amplitude correlations with impairment in CMT1A

Introduction: CMT1A is the most common form of Charcot‐Marie‐Tooth disease (CMT), a slowly progressive neuropathy in which impairment is length dependent. Fibular nerve conduction studies to the anterior tibialis muscle (AT) may serve as a physiological marker of disease progression in patients with CMT1A. The objective of this study is to determine whether the AT compound muscle action potential (CMAP) amplitude correlates with impairment in patients with CMT1A. Methods: We correlated AT CMAP amplitudes and impairment measured by the CMT Neuropathy Score (CMTNS) in a cross‐section of 121 patients with CMT1A and a subset of 27 patients with longitudinal data. Results: AT CMAP amplitudes correlated with impairment as measured by the CMTNS in cross sectional analysis. Longitudinal changes in the AT CMAP showed a strong inverse correlation with leg strength but not other components of the CMTNS. Conclusions: AT CMAP amplitude may serve as a useful outcome measure for physiological changes in natural history studies and clinical trials for patients with CMT1A. Muscle Nerve, 2013     

The relationship of carotid intima-media thickness with anthropometric and metabolic parameters in patients with classic congenital adrenal hyperplasia

Background/aimWe aimed to determine the presence of subclinical atherosclerosis using carotid intima-media thickness (CIMT) and biochemical parameters in children and adolescents with congenital adrenal hyperplasia (CAH).Materials and methods Thirty-four patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency on regular glucocorticoid treatment for ≥3 years and 31 healthy subjects were included in the study. The patients were divided into two groups according to the degree of control of the clinic, laboratory, and radiological parameters as a) “uncontrolled” [n= 22; with increased height velocity (HV) standard deviation score (SDS) (≥2 SDS), advanced bone age, serum 17-OH progesterone <2.0 and ≥10.0 ng/mL or androstenedione <0.3 and ≥ 3.0 ng/mL] or b) “controlled” [n= 12; with HV SDS < 2, bone age (BA)/ chronologic age (CA) ratio < 1.2, serum 17-OH progesterone between 2 and 10 ng/mL and androstenedione between 0.3 and 3.0 ng/mL]. Ultrasonographic examination of carotid artery was performed by the same radiologist using a B-mode ultrasound system.Results There was no significant difference between the CAH and control groups in terms of median (IQR) CIMT values [0.47 (0.05) mm and 0.47 (0.07) mm, respectively; p > 0.05]. When subgroup comparisons were done in terms of median (IQR) CIMT values, there was no significant difference among the controlled, uncontrolled, and healthy control groups [0.45 (0.03) mm, 0.47 (0.04) mm, 0.47 (0.07) mm, respectively; p> 0.05]. In addition, CIMT levels were similar according to sex and disease control status.Conclusion In this study, the CIMT values of CAH cases were similar to those of healthy subjects.     

Risk factors associated with mortality in ıntensive care COVID-19 patients: the importance of chest CT score and intubation timing as risk factors

Background/aim Coronavirus disease 2019 (COVID-19) is a disease with a high rate of progression to critical illness. However, the predictors of mortality in critically ill patients admitted to the intensive care unit (ICU) are not yet well understood. In this study, we aimed to investigate the risk factors associated with ICU mortality in our hospital.Materials and methods In this single-centered retrospective study, we enrolled 86 critically ill adult patients with COVID-19 admitted to ICU of Dokuz Eylül UniversityHospital (İzmir, Turkey) between 18 March 2020 and 31 October 2020. Data on demographic information, preexisting comorbidities, treatments, the laboratory findings at ICU admission, and clinical outcomes were collected. The chest computerized tomography (CT) of the patients were evaluated specifically for COVID-19 and CT score was calculated. Data of the survivors and nonsurvivors were compared with survival analysis to identify risk factors of mortality in the ICU.Results The mean age of the patients was 71.1 ± 14.1 years. The patients were predominantly male. The most common comorbidity in patients was hypertension. ICU mortality was 62.8%. Being over 60 years old, CT score > 15, acute physiology and chronic health evaluation (APACHE) II score ≥ 15, having dementia, treatment without favipiravir, base excess in blood gas analysis ≤ –2.0, WBC > 10,000/mm³, D-dimer > 1.6 µg/mL, troponin > 24 ng/L, Na ≥ 145 mmol/L were considered to link with ICU mortality according to Kaplan–Meier curves (log-rank test, p < 0.05). The APACHE II score (HR: 1.055, 95% CI: 1.021–1.090) and chest CT score (HR: 2.411, 95% CI:1.193–4.875) were associated with ICU mortality in the cox proportional-hazard regression model adjusted for age, dementia, favipiravir treatment and troponin. Howewer, no difference was found between survivors and nonsurvivors in terms of intubation timing.ConclusionsCOVID-19 patients have a high ICU admission and mortality rate. Studies in the ICU are also crucial in this respect. In our study, we investigated the ICU mortality risk factors of COVID-19 patients. We determined a predictive mortality model consisting of APACHE II score and chest CT score. It was thought that this feasible and practical model would assist in making clinical decisions.     

Clinical characteristics and risk factors for 28-day mortality in critically ill patients with COVID-19: a retrospective cohort study

BackgroundTo date, the coronavirus disease 2019 (COVID-19) caused more than 2.6 million deaths all around the world. Risk factors for mortality remain unclear. The primary aim was to determine the independent risk factors for 28-day mortality.Materials and MethodsIn this retrospective cohort study, critically ill patients (≥ 18 years) who were admitted to the intensive care unit due to COVID-19 were included. Patient characteristics, laboratory data, radiologic findings, treatments, and complications were analyzed in the study.ResultsA total of 249 patients (median age 71, 69.1% male) were included in the study. 28-day mortality was 67.9% (n = 169). The median age of deceased patients was 75 (66–81). Of them, 68.6% were male. Cerebrovascular disease, dementia, chronic kidney disease, and malignancy were significantly higher in the deceased group. In the multivariate analysis, sepsis/septic shock (OR, 15.16, 95% CI, 3.96–58.11, p < 0.001), acute kidney injury (OR, 4.73, 95% CI, 1.55–14.46,p = 0.006), acute cardiac injury (OR, 9.76, 95% CI, 1.84–51.83, p = 0.007), and chest CT score higher than 15 (OR, 4.49, 95% CI, 1.51-13.38, p = 0.007) were independent risk factors for 28-day mortality.ConclusionEarly detection of the risk factors and the use of chest CT score might improve the outcomes in patients with COVID-19.