scholarly journals Multisystem Myotilinopathy, including Myopathy and Left Ventricular Noncompaction, due to the MYOT Variant c.179C>T

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Josef Finsterer ◽  
Claudia Stöllberger ◽  
Matthias Hasun ◽  
Korbinian Riedhammer ◽  
Mathias Wagner
Keyword(s):  
Neuromuscular Disorders ◽  
Left Ventricular ◽  
Unknown Etiology ◽  
Multisystem Disease ◽  
Limb Weakness ◽  
Ventricular Noncompaction ◽  
Whole Exome ◽  
History Of ◽  
Myocardial Thickening ◽  
Work Up

Left ventricular hypertrabeculation/noncompaction is a myocardial abnormality of unknown etiology/pathogenesis, which is frequently associated with neuromuscular disorders or chromosomal defects. LVHT in association with a MYOT mutation has not been reported. The patient is a 72-year-old male with a history of strabismus in childhood, asymptomatic creatine-kinase elevation since age 42 years, slowly progressive lower limb weakness since age 60 years, slowly progressive dysarthria and dysphagia since age 62 years, and recurrent episodes of arthralgias and myalgias since age 71 years. He also had arterial hypertension, diverticulosis, hyperlipidemia, coronary heart disease, and a hiatal hernia with reflux esophagitis. Clinical exam revealed mild quadruparesis and proximal wasting of the legs. Whole exome sequencing revealed a known variant in the MYOT gene. Muscle biopsy, previously assessed as inclusion body myopathy, was compatible with the genotype after revision. Cardiologic work-up revealed a left anterior hemiblock, mild myocardial thickening, and noncompaction. This case shows that myotilinopathy may manifest as a multisystem disease, including noncompaction.

Abstract 17212: Whole Exome Sequencing Identifies Novel Genetic Variants in Left Ventricular Noncompaction Cardiomyopathy

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
John Collyer ◽  
Fuyi Xu ◽  
Undral Munkhsaikhan ◽  
Wenying Zhang ◽  
Lu Lu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Left Ventricular ◽  
Left Ventricular Noncompaction ◽  
Ventricular Noncompaction ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
History Of ◽  
Left Ventricular Noncompaction Cardiomyopathy ◽  
Genotype Correlation

Introduction: Causal and modifier genes associated with left ventricular noncompaction (LVNC) often occurring in conjunction with other familial cardiomyopathies remain elusive. Hypothesis: The LVNC-associated di- and multigenic abnormalities can be identified by whole exome sequencing (WES). Methods: Five families with a history of LVNC, including five affected probands, three affected family members, and twelve unaffected relatives, were studied. Genomic DNA was extracted from whole blood samples followed by WES and Sanger sequencing to confirm possibly pathogenic variants predicted by in-silico analysis. Phenotype-genotype correlation and quantitative co-segregation studies are performed. Results: We identified nine missense possibly pathogenic variants, a 2-bp frameshift insertion, and a 9-bp in-frame insertion in the five families. Two affected siblings in Family 1 were found carrying digenic heterozygous variants: c.4048G>A (p.E1350K) in MYH7 and c.827C>T (p.A276V) in ANKRD1. Unaffected parents were carriers for each of the two variants. Three affected members, father and two daughters, of Family 2 carried c.550A>C (p.K184Q) variant in MYH7 in contrast to two unaffected members, mother and another daughter. In Family 3, multigenic heterozygosity (c.673G>T (p.D225Y) in CACNA2D1 ; c.440T>A (p.V147E) in COQ4 and c.3700C>A (p.H1234N) in MYH7) was identified in the proband. These variants were found in none of three unaffected relatives. The proband of Family 4 was positive for heterozygous variants: c.2684_2685insAG (p.A897Kfs*3) in DSC2 , c.8633T>C (p.V2878A) in OBSCN , and c.11717C >T (p.T3906I) in PLEC. The T3906I PLEC variant was identified in his unaffected half-sibling and his father, but not in his mother. In Family 5, c. 2591A>T (p.D864V) in HDAC9 , c.9616C>T (p.R3206W) in PLEC and c.954_955insT (p.L319Sfs*74) in MYH14 were identified in the proband. None of those variants were identified in his unaffected sibling. Conclusions: We report several potential pathogenic LVNC-associated variants in novel genes (ANKRD1, DSC2, OBSCN , PLEC, HDAC9, MYH14, COQ4, CACNA2D1) and known genes ( MYH7 and MYH7B). The diverse profile of inheritance (digenic and multigenic heterogeneity) that may cause and modify the heterogeneous LVNC phenotypes.

Abstract 15632: Phenotypic Overlap Between Left Ventricular Noncompaction and Hypertrophic Cardiomyopathy: A Case Report

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ethan Senser ◽  
Madison Hawkins ◽  
Eric M Williams ◽  
Lauren Gilstrap
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Cardiac Mri ◽  
Genetic Diagnosis ◽  
Lateral Wall ◽  
Anterior Wall ◽  
Left Ventricular ◽  
Ventricular Noncompaction ◽  
History Of ◽  
Clinically Significant

Introduction: Left ventricular non-compaction (LVNC) is characterized by extensively trabeculaed myocardium adjacent to normal compacted myocardium of the left ventricle (LV). Hypertrophic cardiomyopathy (HCM) typically appears as diffuse or segmental LV hypertrophy, with or without outflow tract obstruction. Cardiac sarcomere mutations are present in most HCM cases and have also been identified in LVNC. Whether or not there is clinically significant phenotypic overlap between the two diseases is less well understood. We present a case of known HCM that met criteria for both LVNC and HCM by cardiac MRI. Case: A 49-year old man with HCM due to a c.3742_3759dup variant in MYBPC3 presented to clinic after an episode of syncope and ICD firing. In clinic, the device was interrogated and he was found to have had ventricular flutter which was successfully treated with one shock and a new, high (>20%) burden of premature ventricular beats. An echocardiogram showed a stable ejection fraction at 42%, mild concentric LV hypertrophy without obstruction and a newly dilated LV with an end diastolic diameter of 7.1cm (previously 6.2cm). A cardiac MRI was performed ( Figure ) and showed LV noncompaction and diffuse transmural and mid myocardial hyperenhancement/fibrosis of the septum, basilar lateral wall, anterior wall, and distal right ventricle consistent with patient's long-standing history of hypertrophic cardiomyopathy. Discussion: This case highlights the phenotypic overlap between HCM and LVNC by cardiac MRI. Had this patient not already carried a genetic diagnosis of HCM, he would likely have been diagnosed with LVNC based on this cardiac MRI. The phenotypic overlap in these diseases raises questions about ICD guidelines, the role of anticoagulation and prognosis.

Whole-exome sequencing identify a new mutation of MYH7 in a Chinese family with left ventricular noncompaction

Gene ◽  
2015 ◽  
Vol 558 (1) ◽  
pp. 138-142 ◽  
Author(s):  
Jing Yang ◽  
Meng Zhu ◽  
Yao Wang ◽  
Xiaofeng Hou ◽  
Hongping Wu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Left Ventricular ◽  
Chinese Family ◽  
Left Ventricular Noncompaction ◽  
New Mutation ◽  
Ventricular Noncompaction ◽  
Whole Exome

scholarly journals Cardiac Emerinopathy

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Taisuke Ishikawa ◽  
Hiroyuki Mishima ◽  
Julien Barc ◽  
Masanori P. Takahashi ◽  
Keiichi Hirono ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Left Ventricular ◽  
Cardiac Conduction ◽  
Conduction Disturbance ◽  
Ventricular Noncompaction ◽  
Increased Risk ◽  
Genes Encoding ◽  
History Of ◽  
Cardiac Conduction Defect ◽  
Female Carriers

Background: Mutations in the nuclear envelope genes encoding LMNA and EMD are responsible for Emery-Dreifuss muscular dystrophy. However, LMNA mutations often manifest dilated cardiomyopathy with conduction disturbance without obvious skeletal myopathic complications. On the contrary, the phenotypic spectrums of EMD mutations are less clear. Our aims were to determine the prevalence of nonsyndromic forms of emerinopathy, which may underlie genetically undefined isolated cardiac conduction disturbance, and the etiology of thromboembolic complications associated with EMD mutations. Methods: Targeted exon sequencing was performed in 87 probands with familial sick sinus syndrome (n=36) and a progressive cardiac conduction defect (n=51). Results: We identified 3 X-linked recessive EMD mutations (start-loss, splicing, missense) in families with cardiac conduction disease. All 3 probands shared a common clinical phenotype of progressive atrial arrhythmias that ultimately resulted in atrial standstill associated with left ventricular noncompaction (LVNC), but they lacked early contractures and progressive muscle wasting and weakness characteristic of Emery-Dreifuss muscular dystrophy. Because the association of LVNC with EMD has never been reported, we further genetically screened 102 LVNC patients and found a frameshift EMD mutation in a boy with progressive atrial standstill and LVNC without complications of muscular dystrophy. All 6 male EMD mutation carriers of 4 families underwent pacemaker or defibrillator implantation, whereas 2 female carriers were asymptomatic. Notably, a strong family history of stroke observed in these families was probably due to the increased risk of thromboembolism attributable to both atrial standstill and LVNC. Conclusions: Cardiac emerinopathy is a novel nonsyndromic X-linked progressive atrial standstill associated with LVNC and increased risk of thromboembolism.

Cardiac devices and neuromuscular disorders in left ventricular noncompaction

2011 ◽  
Vol 148 (1) ◽  
pp. 120-123 ◽  
Author(s):  
Claudia Stöllberger ◽  
Hans Keller ◽  
Gerhard Blazek ◽  
Katharina Bichler ◽  
Christian Wegner ◽  
...  
Keyword(s):  
Neuromuscular Disorders ◽  
Left Ventricular ◽  
Left Ventricular Noncompaction ◽  
Ventricular Noncompaction ◽  
Cardiac Devices

Neuromuscular comorbidity, atrial fibrillation and left bundle branch block predict the prognosis of left ventricular hypertrabeculation/noncompaction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Stoellberger ◽  
M Hasun ◽  
M Winkler-Dworak ◽  
J Finsterer
Keyword(s):  
Atrial Fibrillation ◽  
Left Bundle Branch Block ◽  
Neuromuscular Disorders ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Unknown Etiology ◽  
Prognostic Impact ◽  
Bundle Branch Block ◽  
Predictors Of Mortality

Abstract Background The prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT) is controversially assessed. LVHT is frequently associated with neuromuscular disorders (NMDs). Aim of the study was to assess cardiac and neurological findings as predictors of mortality in LVHT-patients. Methods Included were patients with LVHT diagnosed between June 1995 and December 2019 in one echocardiographic laboratory. They underwent a baseline cardiologic examination and were invited for a neurological investigation. In January 2020, their survival status was assessed. Results LVHT was diagnosed in 310 patients (93 female, aged 53±18 years) with a prevalence of 0.4%/year. A neurologic investigation was performed in 205 patients (67%). A specific NMD was found in 33 of the investigated patients (16%), NMDs of unknown etiology in 123 (60%) and the neurological investigation was normal in 49 (24%) patients. During 86 months of follow-up, 59 patients received implanted electronic devices (cardioverter/defibrillator n=21, antibradycardic pacemakers n=11, cardiac resynchronization device/defibrillator n=22, cardiac resynchronization device n=4). During follow-up 105 patients died and 6 patients underwent heart transplantation. The mortality was 4.7%/year. By multivariate analysis, the following baseline parameters were identified as predictors of mortality: increased age (p=0.0005), inpatient-status when LVHT was diagnosed (p=0.0050), presence of a specific NMD (p=0.0187) or NMD of unknown etiology (p=0.0052), atrial fibrillation (p=0.0007) and left bundle branch block (p=0.0168). Conclusions LVHT patients should be systematically investigated neurologically since neurological comorbidity has a prognostic impact. Electrocardiographic abnormalities like atrial fibrillation and left bundle branch block should be considered when planning pharmacotherapy and device-therapy. It has to be assessed by prospective studies, which measures improve the prognosis of LVHT. Funding Acknowledgement Type of funding source: None

scholarly journals Left ventricular noncompaction associated with titin-truncating variants in the TTN gene

2020 ◽  
Vol 25 (10) ◽  
pp. 4027
Author(s):  
Yu. A. Vakhrushev ◽  
T. I. Vershinina ◽  
P. A. Fedotov ◽  
A. A. Kozyreva ◽  
A. M. Kiselev ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Age Groups ◽  
Bioinformatic Analysis ◽  
Left Ventricular ◽  
Left Ventricular Noncompaction ◽  
Ventricular Noncompaction ◽  
Genetic Search ◽  
Reading Frame ◽  
Whole Exome ◽  
New Generation

Aim. To study the association of genetic variants in the titin gene (TTN) with the development and clinical course of left ventricular noncompaction in different age groups.Material and methods. The article discusses three clinical cases of patients with left ventricular noncompaction who were treated at theAlmazovNationalMedicalResearchCenter. We performed a new-generation sequencing of 108 genes associated with cardiomyopathies, as well as whole exome sequencing and Sanger sequencing.Results. We identified genetic variants in the TTN gene leading to the synthesis of truncated protein: in the first two cases, the cause of noncompaction was a thirteen nucleotide deletion with a reading frame shift, in the second, a nonsense mutation. An algorithm for assessing the pathogenicity of the identified variants and a scheme of diagnostic genetic search are presented.Conclusion. Causal role of TTN-truncating variants in development of cardiomyopathies and, in particular, left ventricular noncompaction, requires a comprehensive clinical, segregation and bioinformatic analysis using international databases and the use of bioinformatics software.

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