Risk assessment and genetic counseling for hematologic malignancies-Practice resource of the National Society of Genetic Counselors.

Hematologic malignancies (HMs) are a heterogeneous group of cancers impacting individuals of all ages that have been increasingly recognized in association with various germline predisposition syndromes. Given the myriad of malignancy subtypes, expanding differential diagnoses, and unique sample selection requirements, evaluation for hereditary predisposition to HM presents both challenges as well as exciting opportunities in the ever-evolving field of genetic counseling. This practice resource has been developed as a foundational resource for genetic counseling approaches to hereditary HMs and aims to empower genetic counselors who encounter individuals and families with HMs in their practice.

Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.

Background: Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.

Methods: In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries.

Images: Atypical presentation of congenital central hypoventilation syndrome in an infant with central and obstructive sleep apnea.

Unlabelled: Congenital central hypoventilation syndrome (CCHS), a rare disease caused by paired-like homeobox 2B variants, affects control of breathing. We report on a 21-month-old boy with CCHS caused by a novel nonpolyalanine repeat mutation, neuroblastoma, severe obstructive and central sleep apnea, and sleep-related hypoxemia without hypoventilation. At 10 months, due to persistent central sleep apnea during serial polysomnography, bilevel positive airway pressure therapy was initiated despite the absence of hypoventilation.

A novel mobile health application to support cancer surveillance needs of patients and families with cancer predisposition syndromes.

Background: At least 5%-10% of malignancies occur secondary to an underlying cancer predisposition syndrome (CPS). For these families, cancer surveillance is recommended with the goal of identifying malignancy earlier, in a presumably more curable form. Surveillance protocols, including imaging studies, bloodwork, and procedures, can be complex and differ based on age, gender, and syndrome, which adversely affect adherence.

Nervous system (NS) Tumors in Cancer Predisposition Syndromes.

Genetic syndromes which develop one or more nervous system (NS) tumors as one of the manifestations can be grouped under the umbrella term of NS tumor predisposition syndromes. Understanding the underlying pathological pathways at the molecular level has led us to many radical discoveries, in understanding the mechanisms of tumorigenesis, tumor progression, interactions with the tumor microenvironment, and development of targeted therapies. Currently, at least 7-10% of all pediatric cancers are now recognized to occur in the setting of genetic predisposition to cancer or cancer predisposition syndromes.

Hypertension in pregnancy as an early sex-specific risk factor for cardiovascular diseases: evidence and awareness.

Despite being a physiological condition, human pregnancy is known to cause numerous complications that can endanger the life of the mother and the fetus alike. While the majority of complications are mostly limited within the peripartum period, more and more information is available about persistently higher short- and long-term cardiovascular risk after a pregnancy complicated by a hypertensive disorder. There is evidence that women after gestational hypertension or preeclampsia are more likely to develop arterial hypertension, coronary atherosclerosis, myocardial infarction, stroke, peripheral artery disease, and even diabetes mellitus and venous thromboembolism years after the target pregnancy.

High-sensitivity CRP levels in women with gestational hypertension, preeclampsia and in normotensive pregnant women and its correlations.

Introduction: Gestational hypertension is a less investigated hypertensive disorder of pregnancy than preeclampsia, but evidence exists of an unfavourable cardiovascular profile for women after such a pregnancy.

Aim: To determine serum high-sensitivity C-reactive protein (hs-CRP) levels in women with preeclampsia, gestational hypertension, and in normotensive pregnancy in order to assess the cardiovascular implications and to examine its correlations with some characteristics of women.

Materials And Methods: Thirty-six women with gestational hypertension, thirty-seven with preeclampsia, and fifty maternal and gestational age-matched controls were included in a single-center prospective clinical-epidemiological study.

Acute myeloid leukemia and dilated cardiomyopathy in a pediatric patient with D-2-hydroxyglutaric aciduria type I.

D-2-hydroxyglutaric aciduria (D-2-HGA) is a rare neurometabolic disease with two main subtypes, caused by either inactivating variants in D2HGDH (type I) or germline gain of function variants in IDH2 (type II), that result in accumulation of the same toxic metabolite, D-2-hydroxyglutarate. The main clinical features of both are neurologic, including developmental delay, hypotonia, and seizures. Dilated cardiomyopathy is a unique feature thus far only reported in type II.

Comprehensive Genomic Profiling of High-Risk Pediatric Cancer Patients Has a Measurable Impact on Clinical Care.

Purpose: Profiling of pediatric cancers through deep sequencing of large gene panels and whole exomes is rapidly being adopted in many clinical settings. However, the most impactful approach to genomic profiling of pediatric cancers remains to be defined.

Methods: We conducted a prospective precision medicine trial, using whole-exome sequencing of tumor and germline tissue and whole-transcriptome sequencing (RNA Seq) of tumor tissue to characterize the mutational landscape of 127 tumors from 126 unique patients across the spectrum of pediatric brain tumors, hematologic malignancies, and extracranial solid tumors.

Reticular Dysgenesis: A Rare Immunodeficiency in a Neonate With Cytopenias and Bacterial Sepsis.

Severe combined immunodeficiency (SCID) consists of a group of disorders defined by abnormal B and T cell development that typically results in death within the first year of life if undiagnosed or untreated. Reticular dysgenesis (RD) is a rare but especially severe form of SCID that is caused by adenylate kinase 2 deficiency and is characterized not only by lymphopenia but also by profound neutropenia. RD predisposes patients to viral and fungal infections typical of SCID as well as serious bacterial infections atypical in the neonatal period in other SCID types.

Interleukin-6 and its correlations with maternal characteristics and echocardiographic parameters in pre-eclampsia, gestational hypertension and normotensive pregnancy.

Background: Pre-eclampsia and gestational hypertension are pregnancy-related disorders with major maternal cardiovascular implications later in life.

Objectives: The aim of this study was to determine interleukin-6 levels in women with pre-eclampsia and gestational hypertension and in healthy pregnant controls, and to examine their correlations with characteristics of the women and echocardiographic findings.

Methods: The ELISA method was used to determine serum interleukin-6 in 36 women with gestational hypertension, 37 women with pre-eclampsia and 50 pregnant controls.

Cancer Predisposition in Neonates and Infants: Recognition, Tumor Types, and Surveillance.

Pediatric cancer is rare, and malignancy during the neonatal period even rarer. However, several malignancies can present in infancy, most commonly in the form of solid tumors. Specific cancer types, bilateral or multifocal disease, associated congenital malformations, and/or cancers in close relatives may herald a diagnosis of an underlying cancer predisposition syndrome.

Cancer genetic counseling for childhood cancer predisposition is associated with improved levels of knowledge and high satisfaction in parents.

Previous surveys of adults with cancer have revealed increased levels of genetic knowledge, varying levels of worry, and high satisfaction with cancer genetic counseling. We sought to determine the impact of cancer genetic counseling on parental levels of genetic knowledge, worry about cancer, and satisfaction in the context of suspected cancer predisposition in a child. We hypothesized that parents would be satisfied with cancer genetic counseling and that cancer genetic counseling would improve baseline parental genetic knowledge and decrease levels of worry.

Germline Genetics and Childhood Cancer: Emerging Cancer Predisposition Syndromes and Psychosocial Impacts.

Purpose Of Review: Germline genetic variants contribute to a substantial proportion of cases of cancer in childhood. The purpose of this review is to describe two emerging pediatric cancer predisposition syndromes, including published surveillance protocols, as well as the psychological impacts related to childhood cancer predisposition.

Recent Findings: DICER1 syndrome is pleotropic, predisposing to a variety of tumors and likely phenotypically broader than currently realized.

Hypogammaglobulinemia with decreased class-switched B-cells and dysregulated T-follicular-helper cells in IPEX syndrome.

Early onset multisystem autoimmunity is commonly the defining feature of IPEX. Recurrent sinopulmonary infections and CVID-like phenotype were not previously recognized as a presentation in IPEX. Herein, we describe three extended family members with IPEX.

Verification of Bioanalytical Method for Quantification of Exogenous Insulin (Insulin Aspart) by the Analyser Advia Centaur® XP.

Background: In a number of cases the monitoring of patients with type I diabetes mellitus requires measurement of the exogenous insulin levels. For the purpose of a clinical investigation of the efficacy of a medical device for application of exogenous insulin aspart, a verification of the method for measurement of this synthetic analogue of the hormone was needed. The information in the available medical literature for the measurement of the different exogenous insulin analogs is insufficient.

Reference Values of Certain Serum Indicators of Liver Fibrosis.

Background: Liver fibrosis shows a continuously increasing trend worldwide, due to alcohol abuse, obesity, and, to a lesser extent, chronic hepatitis B and C. Biopsy is still considered the "gold standard" for diagnosis of liver fibrosis. However, it has a number of limitations, such as invasiveness, high cost, need for specialists to conduct and interpret biopsy results, risk of complications, inability to dynamically monitor the pathological process, low patient compliance, and uneven fibrosis distribution.

Albuminuria and Glomerular Filtration in Patients with Essential Hypertension.

Background: Essential hypertension (EH) is a widespread disease. One frequent complication of EH is Chronic Kidney Disease (CKD), whose diagnosis is delayed due to its asymptomatic course. The purpose of this study is to determine the involvement of the kidneys in patients with EH by biomarkers for kidney damage (albuminuria) and glomerular filtration rate (GFR) with creatinine and cystatin C.

[Changes in the hemoglobin A2 level of patients with ischemic heart disease].

40 patients with ischemic heart disease were studied. In 60% of them a higher content of HbA2 was found. These data for higher frequency of HbA2 among the patients with ischemic heart disease do not correspond with the average incidence of the genetically determined anomaly A2-beta-thalassemia among the Bulgarian population.