A phenotype-driven approach to molecular autopsy based in a multidisciplinary team comprising clinical and laboratory genetics, forensic medicine and cardiology is described. Over a 13 year period, molecular autopsy was undertaken in 96 sudden cardiac death cases. A total of 46 cases aged 1-40 years had normal hearts and suspected arrhythmic death. Seven (15%) had likely pathogenic variants in ion channelopathy genes [KCNQ1 (1), KCNH2 (4), SCN5A (1), RyR2(1)]. Fifty cases aged between 2 and 67 had a cardiomyopathy. Twenty-five had arrhythmogenic right ventricular cardiomyopathy (ARVC), 10 dilated cardiomyopathy (DCM) and 15 hypertrophic cardiomyopathy (HCM). Likely pathogenic variants were found in three ARVC cases (12%) in PKP2, DSC2 or DSP, two DCM cases (20%) in MYH7, and four HCM cases (27%) in MYBPC3 (3) or MYH7 (1). Uptake of cascade screening in relatives was higher when a molecular diagnosis was made at autopsy. In three families, variants previously published as pathogenic were detected, but clinical investigation revealed no abnormalities in carrier relatives. With a conservative approach to defining pathogenicity of sequence variants incorporating family phenotype information and population genomic data, a molecular diagnosis was made in 15% of sudden arrhythmic deaths and 18% of cardiomyopathy deaths.

Abnormalities of sex chromosomes are identified in approximately 1% of all pregnancies that undergo a prenatal karyotype. There is a need to review the prenatal as well as postnatal care of the affected mother and offspring.

Methods: Forty patients with proven Fabry disease (mean age 31.7 AE 12.8 years; n = 25 men) were treated prospectively with ERT for 67.2 AE 36.9 months. Before ERT 11 males and 9 females showed LVH, 5 males and 3 females had chronic kidney disease (CKD) and 18 males and 13 females had proteinuria. Results: During follow-up 8 events occurred in 5 patients (2 deaths, 4 ESRD and 1 atrial fibrillation). Sudden death and stroke didń t occurr. Overall population only 3 males and 1 females increased LVMI, the rest reduced or stabilised it. During follow-up, average eGFR were stable in both genders. Conclusions: We found a favourable long term outcome of this cohort under ERT. Our cohort was younger than others and less affected at baseline, so ERT could prevent the progression of the disease towards a fatal organ failure and death.

Introduction Prenatal diagnosis (PND) via amniocentesis or chorionic villus sampling may result in the identification of a sex chromosome abnormality, often as an incidental finding. Aims To ascertain the incidence of sex chromosome abnormalities detected by prenatal diagnosis in the Grampian and the West of Scotland (WoS) regions and to determine the characteristics and outcomes of these cases. Methods Retrospective review of all cases of prenatal diagnoses that revealed a sex chromosome abnormality between 2000 and 2012. Results Over the period of 12 years, 166 positive cases were identified. The indication for PND was an abnormal ultrasound scan in 95(57%), high-risk first trimester screening results in 31(19%), age related aneuploidy risk in 24(14%), maternal anxiety in 9(5%) and a family history of a chromosomal abnormality in 7(4%). Of the 166 cases, 79(48%) cases were 45, X, 24(14%) were 47, XXY, 14(8%) were 48, XXX, 9(5%) were 45, X/46, XX,, 8(5%) had a structurally abnormal X chromosome, 7(4%) were 45X/46XY, 6(4%) were 48, XYY, 2(1%) were 46, XX/46XY and 17(11%) had other variations of sex chromosomes. Of the 166, 73(44%) pregnancies were terminated and of these cases, 47(64%) had a karyotype of 45, X. An additional 7 pregnancies(4%) were associated with an intrauterine death and 5 of these were 45, X. Based on a combined birth rate of 40,000 births per year for these regions, it is estimated that there was one positive case for 3,500 births and approximately half of these led to a live birth. Conclusions 1:7000 births are associated with a prenatally diagnosed sex chromosome abnormality. 45, X is the most commonly encountered abnormality. Given the rare incidence, there is a need to improve our understanding of the care of these cases during the pregnancy as well as afterwards.

Southern Derbyshire Speech and Language Therapy Department has a team of six specialist speech and language therapists who support children with Specific Language Impairment in their mainstream schools via joint commissioning with education. As the team expanded in October 1995 this coincided with health trust and education changes and produced great instability and insecurity within the team. This paper outlines the implementation of a formal team working package using a facilitator provided by the trust's quality team and shows how it is possible to problem solve and develop within a framework of group rules, such as honesty and openness. Following its success its principles have allowed us to co-operate more effectively with both school staff and the community team and to support colleagues through a re-organisation of their service.