Molecular diagnosis of childhood immune dysregulation, polyendocrinopathy, and enteropathy, and implications for clinical management.

BACKGROUND: Most patients with childhood-onset immune dysregulation, polyendocrinopathy, and enteropathy have no genetic diagnosis for their illness. These patients may undergo empirical immunosuppressive treatment with highly variable outcomes. OBJECTIVE: We sought to determine the genetic basis of disease in patients referred with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like (IPEX-like) disease, but with no mutation in FOXP3; then to assess consequences of genetic diagnoses for clinical management. METHODS: Genomic DNA was sequenced using a panel of 462 genes implicated in inborn errors of immunity. Candidate mutations were characterized by genomic, transcriptional, and (for some) protein analysis. RESULTS: Of 123 patients with FOXP3-negative IPEX-like disease, 48 (39%) carried damaging germline mutations in 1 of the following 27 genes: AIRE, BACH2, BCL11B, CARD11, CARD14, CTLA4, IRF2BP2, ITCH, JAK1, KMT2D, LRBA, MYO5B, NFKB1, NLRC4, POLA1, POMP, RAG1, SH2D1A, SKIV2L, STAT1, STAT3, TNFAIP3, TNFRSF6/FAS, TNRSF13B/TACI, TOM1, TTC37, and XIAP. Many of these genes had not been previously associated with an IPEX-like diagnosis. For 42 of the 48 patients with genetic diagnoses, knowing the critical gene could have altered therapeutic management, including recommendations for targeted treatments and for or against hematopoietic cell transplantation. CONCLUSIONS: Many childhood disorders now bundled as "IPEX-like" disease are caused by individually rare, severe mutations in immune regulation genes. Most genetic diagnoses of these conditions yield clinically actionable findings. Barriers are lack of testing or lack of repeat testing if older technologies failed to provide a diagnosis.

Welcoming Healthcare Into Our Virtual Meeting Rooms: Perspective and Perseverance in Pediatric Rheumatology.

Purpose of Review: We highlight practice changes adopted to increased use of telemedicine, look at precision, and accuracy in using a virtual visit to evaluate and treat rheumatic disease, and describe our shift in engaging patients and their families in supporting our research aims. Recent Findings: Telemedicine visits increased substantially with the start of the SARS-CoV-2 pandemic. With this change came the need for significant advances to our telemedicine practices to allow for quality patient visits and continued research collection. Summary: Telemedicine will continue to be an area of increasing importance and has been found to be especially useful for regions like ours which cover many patients in remote areas across Washington, Wyoming, Idaho, Montana, and Alaska. Through the development of new techniques and the use of new technologies, we have been able to improve both the visit quality for patients and our ability to collect research data.

Neuromuscular Control of Vertical Jumps in Female Adolescents.

BACKGROUND: Poor landing mechanics are considered deficits in neuromuscular control and risk factors for lower extremity injury. The Landing Error Scoring System (LESS) has been used to assess the neuromuscular control of landing mechanics for the first landing in a drop vertical jump (DVJ) task. However, the second DVJ landing may provide different results, warranting assessment. HYPOTHESES: (1) LESS scores will differ between first and second DVJ landings across all female participants with (2) greater intraparticipant variability among the second landing compared with the first landing scores. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 13 gymnasts and 31 softball players (N = 44) performed 3 DVJ trials. The mean ± SD age of 44 female athletes was 16.46 ± 2.59 years. The LESS was scored using 2-dimensional video of each trial. RESULTS: There was a significant difference between the first and second DVJ landings (P < 0.01). All participants demonstrated higher LESS scores (worse landing mechanics) during the second DVJ landing (10.10 ± 2.25) than the first landing (6.97 ± 2.72). CONCLUSION: The initial landing in a DVJ has been the focus of neuromuscular control studies using the LESS. This study found worse neuromuscular control during the second DVJ landing, which highlights the importance of evaluating landing mechanics beyond the initial landing. CLINICAL RELEVANCE: LESS analysis of both DVJ landings might improve neuromuscular control screening in female athletes and augment lower extremity and anterior cruciate ligament injury prevention programs.