Monogenic conditions and central nervous system anomalies: A prospective study, systematic review and meta-analysis.

OBJECTIVES: Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities. METHODS: Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model. RESULTS: Thirty studies were included (n = 1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%-36%; I2 = 72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%-34%; I2 = 74%]; (b) single CNS anomaly; 16% [95% CI 10%-23%; I2 = 41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%-40%; I2 = 56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%-57%; I2 = 68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus. CONCLUSIONS: Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.

Management of cardiovascular diseases in HIV/AIDS patients.

Human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome, a pandemic in the current population causes severe weakness of the body's immune system making the infected patient more vulnerable to life-threatening conditions. The disease predisposes the infected patient to several cardiovascular diseases and cerebrovascular diseases such as heart failure and stroke. The decline in CD4 cells following HIV infection, vulnerability to opportunistic infections and underlying HIV pathology plays a major role in the development of cardiovascular manifestations, and treatment targeting cardiomyopathy in this specific patient subset is not well recognized. Patients living with HIV (PLWH) also experience discrimination in receiving cardiovascular disease care and this needs to be addressed by strengthening frameworks for monitoring and providing nonjudgmental healthcare. This review aims to study the profile of the cardiovascular disease in HIV patients, treatment, and provide evidence of the disparity in the provision of healthcare with regard to PLWH.