Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions. TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A.
View Article and Find Full Text PDFBackground: FRMD5 variants were recently identified in patients with developmental delay, ataxia, and eye movement abnormalities.
Objectives: We describe 2 patients presenting with childhood-onset ataxia, nystagmus, and seizures carrying pathogenic de novo FRMD5 variants. Weighted gene co-expression network analysis (WGCNA) was performed to gain insights into the function of FRMD5 in the brain.
Introduction: The prevalence of mental health disorders including anxiety and depression is increasing and is linked to hypertension in healthy individuals. However, the relationship of psychosocial patient-reported outcomes on blood pressure (BP) in primary proteinuric glomerulopathies is not well characterized. This study explored longitudinal relationships between psychosocial patient-reported outcomes and BP status among individuals with proteinuric glomerulopathies.
View Article and Find Full Text PDFPigmented epithelioid melanocytomas (PEM) are intermediate-grade melanocytic lesions with frequent lymph node involvement and rare metastases that tend to follow an indolent course with a favorable outcome. We report two unique cases of congenital PEM with PRKCA fusion transcripts: a multifocal PEM with an aggressive incompletely resectable scalp tumor and a solitary palmar PEM with newly reported ITGB5-PRKCA fusion. Through these case reports and a summary of previously reported cases, we outline the spectrum of disease of PEM and highlight the key clinical and histopathologic features associated with PEM with PRKCA fusion transcripts.
View Article and Find Full Text PDFPurpose: Ferredoxin reductase (FDXR) is a flavoprotein that functions in both iron sulfur cluster biogenesis and steroid biosynthesis pathways in the mitochondria. Not surprisingly, loss of FDXR function causes severe mitochondrial diseases in humans. Although several FDXR-related mitochondriopathy (FRM) cohorts have been reported in the literature, further characterization of the natural history of FRM is warranted.
View Article and Find Full Text PDFBackground: There is a well-documented risk of secondary cutaneous malignancies following allogeneic hematopoietic stem cell transplant (HSCT), but data on risk in pediatric populations are limited. The objective of this study is to perform a systematic review of reported features and outcomes of skin cancers in pediatric allogeneic HSCT recipients.
Methods: MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science were systematically searched (Prospero CRD42022342139).
Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin condition that manifests as painful, deep-seated, inflamed nodules and abscesses in the axillary, groin, perianal, perineal, and inframammary regions. The associated pain, malodour, and disfigurement contribute to its profound negative impact on psychosocial spheres and overall quality of life in affected individuals. Although the symptoms of HS classically begin in the second or third decade of life, HS affects children and adolescents as well.
View Article and Find Full Text PDFBackground: Chronic kidney disease (CKD) is a major health problem, and the risk of CKD and hypertension in children born low birth weight (LBW) is under-recognized. We hypothesized that children born with LBW would have a higher prevalence of reduced kidney function and hypertension.
Methods: Using the National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional study to evaluate whether LBW (< 2500 g), very low birth weight (VLBW < 1500 g), and large birth weight (BW) (> 4000 g) were associated with kidney disease using 4 different estimating equations.
Implementation support through coaching-such as with embedded fidelity assessment, performance feedback, modeling, and alliance building-has been empirically supported as a way to increase and sustain interventionists' fidelity levels. However, education research consistently shows that practitioners struggle to monitor and improve interventionists' fidelity using implementation support strategies. One explanation for this type of implementation research-to-practice gap is that evidence-based coaching strategies have significant limitations with respect to their usability, feasibility, and adaptability.
View Article and Find Full Text PDFSignificance Statement: Renal osteodystrophy (ROD) contributes substantially to morbidity in CKD, including increased fracture risk. Metabolic acidosis (MA) contributes to the development of ROD, but an up-to-date skeletal phenotype in CKD-associated acidosis has not been described. We comprehensively studied associations between acidosis and bone in patients with CKD using advanced methods to image the skeleton and analyze bone-tissue, along with biochemical testing.
View Article and Find Full Text PDFNeuropsychiatric research has been impeded by limited access to human brain tissue, especially from early stages of neurodevelopment when the pathophysiology of many childhood-onset disorders is initiated. Neural organoids are 3-dimensional, self-organizing, multicellular structures generated from pluripotent stem cells that recapitulate some of the cell diversity, cytoarchitecture, and functional features of domains of the developing nervous system. Assembloids are 3-dimensional, self-organizing cultures created by the combination of two or more distinctly patterned organoids or an organoid plus additional cell or tissue type(s) that are used to model cell migration and connectivity.
View Article and Find Full Text PDFOver 20 years after the introduction of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, CKD remains a major public health burden with limited therapeutic options to halt or slow kidney disease progression at all ages. The consensus is that oxidative stress contributes to CKD development and progression. Yet, to date, there is no clear evidence that broad use of antioxidant therapy provides a beneficial effect in CKD.
View Article and Find Full Text PDFBackground: CACNA1C encodes the voltage-gated L-type calcium channel Ca1.2. A specific gain-of-function pathogenic variant in CACNA1C causes Timothy syndrome type 1 (TS1) with cardiac long QT syndrome, syndactyly, and neuropsychiatric symptoms.
View Article and Find Full Text PDFPemphigus vulgaris (PV), an acquired autoimmune bullous disease, is caused by autoantibodies targeting desmosomal proteins in the skin and mucous membranes. Recent data from the adult PV population supports the use of rituximab, a chimeric anti-CD20 IgG1 antibody, as a primary treatment strategy, but limited data exist regarding treatment in the pediatric population. We report the case of a 13-year-old male with PV treated successfully with systemic corticosteroids and rituximab, and review the literature supporting the treatment of pediatric PV with rituximab.
View Article and Find Full Text PDFBackground: Poor linear growth is a consequence of chronic kidney disease (CKD) that has been linked to adverse outcomes. Metabolic acidosis (MA) has been identified as a risk factor for growth failure. We investigated the longitudinal relationship between MA and linear growth in children with CKD and examined whether treatment of MA modified linear growth.
View Article and Find Full Text PDFWe delineated the phenotypic spectrum of epilepsy in individuals with NGLY1 deficiency from an international cohort. We collected detailed clinical and electroencephalographic data from 29 individuals with bi-allelic (likely) pathogenic variants in NGLY1 as part of an ongoing prospective natural history study. Participants were evaluated in-person at a single center and/or remotely.
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