Fetal akinesia deformation sequence syndrome associated with recessive TTN variants.

Arthrogryposis multiplex congenita (AMC) [also known as multiple joints contracture or Fetal Akinesia Deformation Sequence (FADS)] is etiologically a heterogeneous condition with an estimated incidence of approximately 1 in 3000 live births and much higher incidence when prenatally diagnosed cases are included. The condition can be acquired or secondary to fetal exposures and can also be caused by a variety of single-gene disorders affecting the brain, spinal cord, peripheral nerves, neuromuscular junction, muscle, and a variety of disorders affecting the connective tissues (Niles et al., Prenatal Diagnosis, 2019; 39:720-731). The introduction of next-generation gene sequencing uncovered many genes and causative variants of AMC but also identified genes that cause both dominant and recessive inherited conditions with the variability of clinical manifestations depending on the genes and variants. Molecular diagnosis in these cases is not only important for prognostication but also for the determination of recurrence risk and for providing reproductive options including preimplantation and prenatal diagnosis. TTN, the largest known gene in the human genome, has been known to be associated with autosomal dominant dilated cardiomyopathy. However, homozygote and compound heterozygote pathogenic variants with recessive inheritance have rarely been reported. We report the effect of recessive variants located within the fetal IC and/or N2BA isoforms in association with severe FADS in three families. All parents were healthy obligate carriers and none of them had cardiac or skeletal muscle abnormalities. This report solidifies FADS as an alternative phenotypic presentation associated with homozygote/compound heterozygous pathogenic variants in the TTN.

Progressive brain atrophy and severe neurodevelopmental phenotype in siblings with biallelic COASY variants.

Biallelic pathogenic variants in the COASY gene have been associated with two distinct disease phenotypes, that is, COASY-protein associated neurodegeneration (CoPAN) and pontocerebellar hypoplasia type 12 (PCH 12). We present two siblings that independently presented with significant hypotonia and respiratory insufficiency at birth. Comprehensive genetic testing revealed homozygous variants within COASY, however, the progressive clinical and neuroradiologic findings described here are unique and have not been described previously. Magnetic resonance imaging showed progressive diffuse parenchymal loss throughout the bilateral cerebral hemispheres and atrophy of the basal ganglia and brainstem. As such, this article brings forth two additional cases of COASY-related disorder with abnormal newborn screening acylcarnitine profiles resembling carnitine palmitoyl transferase 1a (CPT1a) deficiency in two siblings who presented at birth with contractures, marked hypotonia and absent respiratory drive.

Maternal vitamin K deficient embryopathy: association with hyperemesis gravidarum and Crohn disease.

Chondrodysplasia punctata (CDP) is an etiologically heterogeneous disorder characterized by the radiographic finding of stippled epiphyses (punctate calcifications). It is often accompanied by a characteristic facial appearance, known as the Binder phenotype, which is attributed to hypoplasia of the nasal cartilages; abnormal distal phalanges (brachytelephalangy) are a common component manifestation as well. We report eight patients with a Binder phenotype with or without CDP who all shared a known or suspected maternal deficiency of vitamin K. We suspect that this phenotype is probably under recognized, and we hope to increase awareness about the maternal risk factors, especially hyperemesis gravidarum, which lead to nutritional deficiency.

Comparative outcome of oesophagogastric cancer in younger patients.

INTRODUCTION: The incidence of oesophageal and gastric cardia adenocarcinoma has increased rapidly over the previous two decades. There has been a rise in the number of younger patients affected, and the disease may be more aggressive and have a worse prognosis in these individuals. Current UK guidelines for urgent cancer referral focus on patients who are over 55 years. This study prospectively compares the referral times and outcome in a cohort of patients diagnosed with oesophagogastric cancer under the age of 55 years with a matched cohort over 55 of age. PATIENTS AND METHODS: Every patient diagnosed with oesophageal, junctional or gastric cancer under the age of 55 years and every subsequent patient over the age of 55 years was accepted into this study. In all, 17 hospitals participated over a 12-month period. The following data were recorded: duration of symptoms, number of fast-track referrals, duration from GP referral to first hospital visit and stage at presentation. A survival analysis between the two groups was conducted at 2 years after the end of recruitment. RESULTS: In total, 102 patients under the age of 55 years were diagnosed with oesophagogastric cancer during the study period. There were fewer fast-track referrals from GPs in this group compared to the over 55-year matched cases (29.4% vs 40.2%). Duration of time from GP referral to first hospital visit was significantly longer in the under 55-year group (median 14 days vs 11 days; P = 0.045 Mann-Whitney). Stage at presentation was similar between groups, but a higher proportion of patients under 55 years were offered a curative treatment plan compared to those over 55 years (P < 0.01). Survival analysis conducted at 2 years after the end of recruitment demonstrated a longer median survival in the under 55-year group (348 days vs 248 days; P = 0.03 log rank). CONCLUSIONS: Although there was a longer referral time in patients under the age of 55 years, this had no effect on disease stage at presentation. Patients under the age of 55 years diagnosed with oesophageal or gastric cancer appear to have a better prognosis than those aged over 55 years.

A case report of evidence-based practice: from academia to clinic.

The purpose of this article is to present activities that can be used to integrate evidence-based practice (EBP) into clinicians' daily work so that they may be better informed when planning intervention with their clients. The article includes a short history of EBP, a description of an eight-step EBP process taught in an academic setting using a student project as an example, and suggestions for ways in which individual practitioners and occupational therapy managers can promote the implementation of EBP in daily practice.

Qualitative data analysis: challenges and dilemmas related to theory and method.

The purpose of this article is to initiate a discussion of the struggles and challenges we encountered as we developed a method of analysis for a particular qualitative study. We present our thinking process showing the questions that arose, the theoretical ideas on which we relied, and the decisions we made at crucial junctures. Portions from several theoretical frames used as the basis for the analysis are presented and include Polkinghorne's (1995) narrative inquiry, Glaser and Strauss's (1967) and Charmaz's (2000) grounded theory, Riessman's (1990b) mixed approach to analysis, and Rosaldo's (1989) ideas on reflexivity. Examples from the study are used to illustrate points in the analysis.

Understanding others: a course to learn interactive clinical reasoning.

SUMMARY Teaching future practitioners to use clinical reasoning processes is necessary for entry-level practice. While there are numerous articles addressing some aspects of clinical reasoning, none describe a course solely focused on understanding another person's perspective-interactive clinical reasoning. The article describes an Interactive Clinical Reasoning course for entry-level graduate students-one of four seminars on clinical reasoning embedded in a curriculum that simultaneously uses an infusion model to increase cultural awareness and sensitivity. The underlying philosophy of the course includes using interpersonal intelligence (Gardner, 1985) to "treat a patient's illness experience" (Mattingly, 1992, p. 4). Clients are the experts of their own experience with illness or disability, and students must pay as much attention to their questions and their own reactions as to their interviewee's responses. Readings, videotapes, assignments, and class exercises designed to increase students' interviewing skills and their ability to understand each client's perspective are described.