Inferolateral Fibrosis in a Nonhypertrophic Left Ventricle.

A 62-year-old recreational cyclist presented with transient loss of consciousness and common electrocardiographic findings. Despite absence of left ventricular hypertrophy, multidisciplinary evaluation and a positive family history led to the diagnosis of non-classical Fabry disease. This case emphasizes the added value of multidisciplinary analysis of nonspecific findings to diagnose a rare disease.

Recreational and Occupational Physical Activity and Risk of Adverse Events in Truncating Founder Variant Carriers.

Background: founder variants cause hypertrophic cardiomyopathy leading to heart failure and malignant ventricular arrhythmias. Exercise is typically regarded as a risk factor for disease expression although evidence is conflicting. Stratifying by type of exercise may discriminate low- from high-risk activities in these patients.

Timing of cerebral damage in molybdenum cofactor deficiency: A meta-analysis of case reports.

Purpose: Molybdenum cofactor deficiency (MoCD) classically presents shortly after birth, with neurological symptoms ascribed to postnatal toxicity of accumulating sulphite. Case reports suggest that cerebral damage associated with MoCD may have a prenatal onset.

Methods: A meta-analysis of case reports was performed on individuals with genetically proven MoCD retrieved through a systematic review and in-house search.

Long-term prognosis of patients with an SCN5A loss-of-function variant and progressive cardiac conduction disorder or Brugada syndrome.

Background: The long-term prognosis of patients with a loss-of-function variant in the cardiac sodium channel gene SCN5A is unknown.

Objective: This study aimed to evaluate the long-term arrhythmic risk in patients with an SCN5A loss-of-function variant to identify predictors of arrhythmic events.

Methods: Probands and family members with (likely) pathogenic SCN5A loss-of-function variants were retrospectively included.

Vascular Ehlers-Danlos Syndrome: A Comprehensive Natural History Study in a Dutch National Cohort of 142 Patients.

Background: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder with a high risk for arterial, bowel, and uterine rupture, caused by heterozygous pathogenic variants in . The aim of this cohort study is to provide further insights into the natural history of vEDS and describe genotype-phenotype correlations in a Dutch multicenter cohort to optimize patient care and increase awareness of the disease.

Methods: Individuals with vEDS throughout the Netherlands were included.

Are disease-specific patient-reported outcomes measures (PROMs) used in cardiogenetics? A systematic review.

Patient-reported outcome measures (PROMs) are used to facilitate patient-centered care (PCC). While studies in patients with cardiac conditions have revealed poorer health-related quality of life (HRQoL) and elevated emotional stress, studies in inherited cardiac conditions (ICC) seem rare. A systematic review evaluated which (specific domains of) PROMs are used in patients with ICC.

Outcomes in Dutch DPP6 risk haplotype for familial idiopathic ventricular fibrillation: a focused update.

Background: The genetic risk haplotype DPP6 has been linked to familial idiopathic ventricular fibrillation (IVF), but the associated long-term outcomes are unknown.

Methods: DPP6 risk haplotype-positive family members (DPP6 cases) and their risk haplotype-negative relatives (DPP6 controls) were included. Clinical follow-up data were collected through March 2023.

Newborn screening for primary carnitine deficiency: who will benefit? - a retrospective cohort study.

Background: Newborn screening (NBS) programmes identify a wide range of disease phenotypes, which raises the question whether early identification and treatment is beneficial for all. This study aims to answer this question for primary carnitine deficiency (PCD) taking into account that NBS for PCD identifies newborns with PCD and also until then undiagnosed mothers.

Methods: We investigated clinical, genetic (variants in gene) and functional (carnitine transport activity in fibroblasts) characteristics of all referred individuals through NBS (newborns and mothers) and clinically diagnosed patients with PCD (not through NBS).

Untargeted Metabolomics Identifies Potential Hypertrophic Cardiomyopathy Biomarkers in Carriers of Founder Variants.

Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by pathogenic variants, and a significant cause of sudden cardiac death. Severity is highly variable, with incomplete penetrance among genotype-positive family members. Previous studies demonstrated metabolic changes in HCM.

Deleterious, protein-altering variants in the transcriptional coregulator ZMYM3 in 27 individuals with a neurodevelopmental delay phenotype.

Neurodevelopmental disorders (NDDs) result from highly penetrant variation in hundreds of different genes, some of which have not yet been identified. Using the MatchMaker Exchange, we assembled a cohort of 27 individuals with rare, protein-altering variation in the transcriptional coregulator ZMYM3, located on the X chromosome. Most (n = 24) individuals were males, 17 of which have a maternally inherited variant; six individuals (4 male, 2 female) harbor de novo variants.

Reclassification of a likely pathogenic Dutch founder variant in KCNH2; implications of reduced penetrance.

Background: Variants in KCNH2, encoding the human ether a-go-go (hERG) channel that is responsible for the rapid component of the cardiac delayed rectifier K+ current (IKr), are causal to long QT syndrome type 2 (LQTS2). We identified eight index patients with a new variant of unknown significance (VUS), KCNH2:c.2717C > T:p.

A mild case of sodium-dependent multivitamin transporter (SMVT) deficiency illustrating the importance of treatment response in variant classification.

Sodium-dependent multivitamin transporter (SMVT) deficiency is a recently described multivitamin-responsive inherited metabolic disorder (IMD) of which the phenotypic spectrum and response to treatment remains to be elucidated. So far, four pediatric patients have been described in three case reports with symptoms ranging from severe neurodevelopmental delay to feeding problems and failure to thrive, who demonstrated significant improvement after initiation of enhancement of targeted multivitamin treatment (biotin, pantothenic acid, and lipoic acid). We describe a fifth case of a patient presenting at the relatively mild end of the phenotypic spectrum with failure to thrive, frequent vomiting and metabolic acidosis with hypoglycemia, and mild osteopenia, who was diagnosed with SMVT deficiency due to compound heterozygous variants in Additional genetic testing of variants of unknown significance (VUSs) as well as the clinical improvement in all aspects of the patient's disease upon initiation of treatment with biotin and pantothenic acid (plus lipoate as antioxidant) aided in the confirmation of this diagnosis.

Pregnancy in women with Brugada syndrome: Is there an increased arrhythmia risk? A case-series report.

Introduction: In some rare arrhythmia syndromes, arrhythmia risk in female patients increases during pregnancy, necessitating extra controls. We wanted to evaluate if the increased risk for arrhythmia during pregnancy applies in women with Brugada syndrome and their potentially affected fetuses.

Methods: A comprehensive literature search was performed on PubMed (MeSH search terms "Brugada syndrome," "pregnancy," "parturition," "labor," "delivery," "fetal death," and "stillbirth").

Adult GAMT deficiency: A literature review and report of two siblings.

Guanidinoacetate methyltransferase (GAMT) deficiency is a creatine deficiency disorder and an inborn error of metabolism presenting with progressive intellectual and neurological deterioration. As most cases are identified and treated in early childhood, adult phenotypes that can help in understanding the natural history of the disorder are rare. We describe two adult cases of GAMT deficiency from a consanguineous family in Pakistan that presented with a history of global developmental delay, cognitive impairments, excessive drooling, behavioral abnormalities, contractures and apparent bone deformities initially presumed to be the reason for abnormal gait.