Genetics and Clinical Genomics

Current genomic diagnostic challenges in Hemophagocytic Syndromes in pediatrics: Case report

Juan Manuel Sánchez-Vargas, Lina Johanna Moreno Giraldo — Tue, 30 Apr 2024 00:00:00 -0500

Introduction: Familial hemophagocytic lymphohistiocytosis (FHL) is a disease of the autoimmune system that presents with an excessive inflammatory syndrome caused by activated T lymphocytes and histiocytosis. It occurs with autosomal recessive inheritance linked to the chromosome X. Approximately 90% of diagnosed children are under 2 years of age and the incidence is approximately 0.12 per 100,000. It can be divided into five subtypes depending on the causative genetic variant. The most involved pathogenic variants are in the perforin 1 (PRF1) and UNC-13 protein homolog D (UNC13D) genes.

Clinical case: The case of an 11-year-old preadolescent is presented, with a history of recurrent infections, who presents with convulsive syndrome associated with fever, low weight and height for age, hepatomegaly and cognitive disability. In the initial approach, infectious, immunological, hematological, metabolic and oncological diseases are ruled out. The clinical exome for primary immunodeficiencies shows a homozygous pathogenic variant p.A91V in the PRF1 gene of autosomal recessive inheritance, a result related to familial hemophagocytic lymphohistiocytosis type 2 (FHL2).

Discussion and conclusion: The altered PRF1 conformational change reduces the cytotoxic activity of the protein and causes disease. Patients carrying defects in the PRF1 gene are vulnerable to infections, autoimmune diseases and malignant tumors. With a defined and precise diagnosis, it is possible to guide health actions, follow-up guidelines, evaluation of heritability risk through an index case in order to find other possible carriers, carry out complete genetic counseling, implement and initiate targeted treatments that reduce the morbidity and mortality associated with this pathology. Currently, there are several studies in different phases of research on molecules that may intervene in the natural history of the disease.

Aggrecanopathies: Report of a Spondyloepiphyseal Dysplasia Kimberley type (SEDK) in a family, caused by a previously undescribed likely pathogenic variant of the ACAN gene

Enrique Daniel Austin-Ward, Jean Villegas — Tue, 30 Apr 2024 00:00:00 -0500

The study of patients with short stature is complex and requires diagnostic algorithms in which the evaluation by Genetics is essential, seeking to rule out genetic syndromes that may explain the patient's manifestations. Among these possible causes, skeletal dysplasias should always be considered as a diagnostic possibility. We present the case of a family in which in the proband and in his progenitor a previously undescribed probably pathogenic variant was detected in the ACAN gene which encodes the Aggrecan Proteoglycan (PG), a fundamental component in the endochondral bone growth and in the articular cartilage, and whose alteration in heterozygous state produces Kimberley type Skeletal Spóndyloepiphyseal Dysplasia (SEDK) and other disorders known as aggrecanopathies. Molecular genetic analyses are becoming mandatory studies to achieve an accurate diagnosis in these cases. It is expected that the study of these conditions will shed light for a better understanding of the pathophysiology of osteoarthritis and for the development of new treatments for its management, given its high prevalence in older adults and the fact that aggrecan degeneration plays a central role in it.

Characterization and prevalence of comorbidities in pediatric patients with Down syndrome in the Dominican Republic

Katlin De La Rosa Poueriet, Andrea Irina Servalle Mella, Bary Bigay Mercedes — Tue, 30 Apr 2024 00:00:00 -0500

This study analyzes the prevalence and characteristics of comorbidities in 534 children with Down Syndrome (DS) in the Dominican Republic, between 2018 and 2022. The research reveals early detection of DS, with an equal gender distribution. Most cases resulted from nondisjunction, with a significant association between advanced maternal age and increased risk of DS. About 62.2% of the children had comorbidities, with cardiac conditions being the most prevalent, followed by endocrine and neurologic comorbidities, mainly hypothyroidism and seizure disorders. Ophthalmic and otorhinolaryngologic conditions were also common, with strabismus and hypoacusis standing out. The findings emphasize the need for early and comprehensive management adapted to the individual and regional characteristics of patients with DS.

Membranous nephropathy: genetics, antigens and antibodies

Karen Courville, Norman Bustamante — Tue, 30 Apr 2024 00:00:00 -0500

Membranous nephropathy is a kidney disorder characterized by thickening of the glomerular basement membrane, that causes nephrotic syndrome. It can be caused by various underlying conditions that result in damage to the filtering units of the kidneys, known as nephrons, producing massive proteinuria, hypoalbuminemia, edema and hyperlipidemia. Between 30 to 40% of cases of nephrotic syndrome in adults are due to membranous nephropathy.

In recent decades, progress has been made with the discovery of antigens, antibodies and genes involved in the pathophysiology of the disease and a new classification system has been proposed. The presence of antigen-antibody complexes together with genetic factors may influence the susceptibility to such immune dysregulation, and states new information in a what was known between the etiologies of primary and secondary causes.

The understanding of the antigens involved in membranous nephropathy is an area of active research, and additional antigens may be identified as our knowledge of the disease continues to evolve. This article summarizes some concepts and recent findings made on this topic.

Awareness of rare genetic diseases in daily clinical practice

Jorge D. Méndez-Ríos — Tue, 30 Apr 2024 00:00:00 -0500

In this issue, we are pleased to present 4 multidisciplinary papers that include disciplines such as Pediatric Genetics, Hematology, and Nephrology. These high quality papers represent the efforts of months of specialist colleagues in the area of multidisciplinary clinical genetics. Each contribution represents a tool for education and teaching at multiple levels of medical learning.

Editorial Team - Vol 2 Num 1 2024

Journal Genetics and Clinical Genomics — Wed, 01 May 2024 00:00:00 -0500

Summary

Year 2023, Volume 1, Issue 3
Published: December 31th, 2023

Editors and Reviewers

The following team of professionals from different health areas participated in the preparation of this issue.

Jorge D. Méndez-Ríos, MD, MS, PhD.
Physician and Molecular Geneticist – Canada

Lorena Salazar García, PhD.
Molecular Geneticist – Spain

Dra. Lina Johanna Moreno Giraldo, MD.
Pediatric Geneticist – Colombia

Dr. Indira Herrera
Pediatric Geneticist - Republic of Panama

Dr. Johan Serrano.
Internal Medicine - Republic of Panama