Women and Alport syndrome

X-linked Alport syndrome (XLAS) is caused by mutations in type IV collagen causing sensorineural hearing loss, eye abnormalities, and progressive kidney dysfunction that results in near universal end-stage renal disease (ESRD) and the need for kidney transplantation in affected males. Until recent decades, the disease burden in heterozygous “carrier” females was largely minimized or ignored. Heterozygous females have widely variable disease outcomes, with some affected females exhibiting normal urinalysis and kidney function, while others develop ESRD and deafness. While the determinants of disease severity in females with XLAS are uncertain, skewing of X-chromosome inactivation has recently been found to play a role. This review will explore the natural history of heterozygous XLAS females, the determinants of disease severity, and the utility of using XLAS females as kidney donors

Kidney transplantation in childhood: mental health and quality of life of children and caregivers

Our objective was to assess the mental health and health-related quality of life (HRQOL) in children and their parents after renal transplantation (TX) compared to healthy controls and children with acute lymphoblastic leukemia (ALL) and to identify possible health status variables associated with impaired mental health and HRQOL. Thirty-eight TX children with a median age of 13 (range 3–19) years were investigated. Mental health was assessed by the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and the Strength and Difficulties Questionnaire (SDQ-20). Each mother’s own mental health and QOL were assessed by the General Health Questionnaire (GHQ-30) and the Quality of Life Scale (QOLS). Forty children with ALL [median age 11 (8.5–15.4) years] and 42 healthy children [median age 11 (8.9– 15) years] served as controls. Treadmill exercise results from 22 of the 38 patients were included in the analysis. TX children showed significantly higher levels of mental health problems and lower HRQOL at 2 to 16 years after transplantation compared to both control groups. Body mass index and maximal oxygen uptake (n = 22/38) were significant predictors of child mental health (SDQ) and child QOL (PedsQL), respectively. Based on these results, we suggest that rehabilitation after TX should include a focus on physical activity and QOL to reduce interconnected physical and psychological morbidity in kidney TX children

Implementing core outcomes in kidney disease: report of the Standardized Outcomes in Nephrology (SONG) implementation workshop

There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes

De novo SCN1A mutations in migrating partial seizures of infancy

Objective: To determine the genetic etiology of the severe early infantile onset syndrome of malignant migrating partial seizures of infancy (MPSI). Methods: Fifteen unrelated children with MPSI were screened for mutations in genes associated with infantile epileptic encephalopathies: SCN1A, CDKL5, STXBP1, PCDH19, and POLG. Microarray studies were performed to identify copy number variations. Results: One patient had a de novo SCN1A missense mutation p.R862G that affects the voltage sensor segment of SCN1A. A second patient had a de novo 11.06 Mb deletion of chromosome 2q24.2q31.1 encompassing more than 40 genes that included SCN1A. Screening of CDKL5 (13/15 patients), STXBP1 (13/15), PCDH19 (9/11 females), and the 3 common European mutations of POLG (11/15) was negative. Pathogenic copy number variations were not detected in 11/12 cases. Conclusion: Epilepsies associated with SCN1A mutations range in severity from febrile seizures to severe epileptic encephalopathies including Dravet syndrome and severe infantile multifocal epilepsy. MPSI is now the most severe SCN1A phenotype described to date. While not a common cause of MPSI, SCN1A screening should now be considered in patients with this devastating epileptic encephalopathy.D. Carranza Rojo... L.M. Dibbens... J.C. Mulley... et al