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Biallelic pathogenic variants in the TANGO2 (transport and Golgi organization 2 homolog) gene have been identified as causing a rare metabolic disorder characterized by susceptibility to recurrent rhabdomyolysis, lactic acidosis, encephalopathy, and life-threatening tachyarrhythmias. Recently published reports suggest variable clinical severity and phenotypes. This study details five new patients from two families with biallelic pathogenic variants in the TANGO2 gene identified by whole exome sequencing and includes the largest number of affected individuals from a single family reported to date. We document significant intrafamilial variability and highlight that milder phenotypes may be underrecognized. We present biochemical and clinical data to help highlight the features that aid in consideration of this condition in the differential with disorders of fatty acid oxidation. We also present a comprehensive literature review summarizing the molecular, clinical, and biochemical findings for 92 individuals across 13 publications. Of the 27 pathogenic variants reported to date, the recurrent exons 3-9 deletion represents the most common variant seen in 42% of individuals with TANGO2 deficiency. Common clinical features seen in >70% of all individuals include acute metabolic crisis, rhabdomyolysis, neurologic abnormalities, developmental delay, and intellectual disability. Findings such as elevated creatine kinase, hypothyroidism, ketotic hypoglycemia, QT prolongation, or abnormalities of long-chain acylcarnitines and urine dicarboxylic acids should raise clinical suspicion for this life-threatening condition.

Summary Robinow syndrome (RS) is a genetically heterogeneous disorder with six genes that converge on the WNT/planar cell polarity (PCP) signaling pathway implicated (DVL1, DVL3, FZD2, NXN, ROR2, and WNT5A). RS is characterized by skeletal dysplasia and distinctive facial and physical characteristics. To further explore the genetic heterogeneity, paralog contribution, and phenotypic variability of RS, we investigated a cohort of 22 individuals clinically diagnosed with RS from 18 unrelated families. Pathogenic or likely pathogenic variants in genes associated with RS or RS phenocopies were identified in all 22 individuals, including the first variant to be reported in DVL2. We retrospectively collected medical records of 16 individuals from this cohort and extracted clinical descriptions from 52 previously published cases. We performed Human Phenotype Ontology (HPO) based quantitative phenotypic analyses to dissect allele-specific phenotypic differences. Individuals with FZD2 variants clustered into two groups with demonstrable phenotypic differences between those with missense and truncating alleles. Probands with biallelic NXN variants clustered together with the majority of probands carrying DVL1, DVL2, and DVL3 variants, demonstrating no phenotypic distinction between the NXN-autosomal recessive and dominant forms of RS. While phenotypically similar diseases on the RS differential matched through HPO analysis, clustering using phenotype similarity score placed RS-associated phenotypes in a unique cluster containing WNT5A, FZD2, and ROR2 apart from non-RS-associated paralogs. Through human phenotype analyses of this RS cohort and OMIM clinical synopses of Mendelian disease, this study begins to tease apart specific biologic roles for non-canonical WNT-pathway proteins., Robinow syndrome (RS) is a genetically heterogeneous disorder caused by WNT/PCP-signaling dysfunction. We identified pathogenic variants in RS individuals (n = 22), including the first DVL2 variant. Quantitative HPO-term-based analyses unveiled gene/allele-specific correlations to disease traits, providing a model for delineating the phenotypic consequences of variants affecting paralogs in the same pathway.

Introduction Biased language influences health care providers' perceptions of patients, impacts their clinical care, and prevents vulnerable populations from seeking treatment. Training clinicians to systematically replace biased verbal and written language is an essential step to providing equitable care. Methods We designed and implemented an interactive workshop to teach health care professionals a framework to identify and replace stigmatizing language in clinical practice. The workshop included a reflective exercise, role-play, brief didactic session, and case-based discussion. We developed the program for a broad target audience of providers and initially delivered it at three academic conferences. We used descriptive statistics to analyze Likert-style items on course evaluations and identified themes in open-text responses. Results A total of 66 participants completed course evaluations; most believed the workshop met its objectives (4.8 out of 5.0) and strongly agreed that they would apply skills learned (4.8). Participants planned to incorporate reflection into their verbal and written language. Potential barriers to applying course content included perceived difficulty in changing entrenched practice habits, burnout, and fatigue. Suggestions for improvement included more time for group discussions and strategies to teach skills to colleagues. Discussion Participants found the course material highly engaging and relevant to their clinical practice. Learners left the workshop feeling motivated to engage in more mindful word choice and to share key concepts with their colleagues.

This study examined the predictors of participation in step down continuing care in publicly funded substance abuse treatment programs, and the relation between participation in step down care and alcohol and crack cocaine use outcomes over a 36-month follow-up. The sample included patients in residential/inpatient programs (IP; N=134) and intensive outpatient programs (IOP; N=370). About one-third of patients in the IP sample received step down IOP or standard outpatient (OP) continuing care, and less than a quarter of those in the IOP sample received step down OP care. Patients who received step down continuing care following IP had greater social support at intake and were more likely to be female and White than those who did not receive continuing care. Patients who received continuing care following IOP were more likely than those who did not to be female and employed, and were older, had higher self-efficacy, and shorter lengths of stay in IOP. Participation in step down care was not associated with other factors assessed at intake. In the IP sample, receiving step down continuing care was not associated with better alcohol or crack cocaine use outcomes over the 36-month follow-up. In the IOP sample, there were also no main effects favoring continuing care for either alcohol or crack cocaine use outcomes. However, patients who received continuing care did have less crack cocaine use in the first six months of the follow-up. These findings suggest that new models of continuing care are needed that are more acceptable to patients, produce better outcomes, and are cost-effective.