BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.

• MeSH
• Cardiomyopathy, Dilated * genetics   MeSH
• Adult MeSH
• Phenotype MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Ventricular Remodeling genetics   MeSH
• Arrhythmias, Cardiac complications   epidemiology   genetics   MeSH
• Cardiac Myosins genetics   MeSH
• Heart Failure * complications   genetics   MeSH
• Myosin Heavy Chains * genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Although genetic variants in MYH7 are the most frequent cause of pediatric genetic dilated cardiomyopathy (DCM), there are no studies available describing this entity. We sought to describe clinical features, analyze variant location, and explore predictors of bad prognosis in pediatric MYH7-related DCM. METHODS AND RESULTS: We evaluated clinical records from 44 patients (24 men; median age at diagnosis, 0.54 [interquartile range, 0.01-10.8] years) with pathogenic/likely pathogenic variants in MYH7 diagnosed with DCM at pediatric age (<18 years) followed at 13 international centers. We also explored risk factors associated with a composite end point of end-stage heart failure defined as heart transplantation or heart failure-related death. Twenty-two patients (50%) were diagnosed at age <6 months, including 7 (16%) at birth. Left ventricular (LV) hypertrabeculation features were present in 15 (38%), particularly among patients with genetic variants in the head domain. After a median follow-up of 6.1 years (interquartile range, 1.9-13.4), 15 patients (36%) required a heart transplant (n=14) or died due to end-stage heart failure (n=1), 15 patients (36%) persisted with systolic dysfunction despite treatment, 12 (29%) had a significant increase in LV ejection fraction, and 2 were lost to follow-up. Overall, end-stage heart failure event rate was 25% at 5 years. New York Heart Association class III to IV (hazard ratio [HR], 7.67 [95% CI, 2.16-27.2]; P=0.002) and LV ejection fraction ≤35% (HR, 4.00 [95% CI, 1.11-14.4]; P=0.03) were the best predictors of bad prognosis. CONCLUSIONS: Pediatric MYH7-related DCM is characterized by early onset, frequent LV hypertrabeculation, and poor prognosis. Advanced New York Heart Association class and low LV ejection fraction emerged as predictors of end-stage heart failure.

• MeSH
• Cardiomyopathy, Dilated * genetics   physiopathology   diagnosis   MeSH
• Child MeSH
• Phenotype MeSH
• Ventricular Function, Left MeSH
• Genetic Predisposition to Disease MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Mutation MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Prognosis MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Cardiac Myosins * genetics   MeSH
• Heart Failure genetics   physiopathology   diagnosis   MeSH
• Myosin Heavy Chains * genetics   MeSH
• Heart Transplantation * MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

• MeSH
• Cardiomyopathy, Hypertrophic genetics   MeSH
• Humans MeSH
• Mutation, Missense MeSH
• DNA Mutational Analysis MeSH
• Codon, Nonsense MeSH
• Cardiac Myosins MeSH
• Amino Acid Substitution MeSH
• Myosin Heavy Chains genetics   MeSH
• Check Tag
• Humans MeSH

Detetion of mutations in exons 14,16,20.23 of gene coding for heavy chain of B-myosin(MYH7)by means of DGGE,SSCP on capillary electrophoresis and direct sequencing. Mutations on DNA of MYH7 are frequent cause of familiar hypertrophic cardiomyopathies.

Detekce mutací v exonech 14,16,20,23 genu pro těžký řetězec beta-myosinu (MYH7) pomocí DGGE, SSCP na kapilární elektroforéze a přímé sekvenace. Mutace na DNA v genu MYH7 jsou častou příčinou familiárních hypertrofických kardiomyopatií.

• MeSH
• Cardiomyopathy, Hypertrophic, Familial genetics   MeSH
• Genetic Testing methods   MeSH
• Mutation MeSH
• Polymerase Chain Reaction MeSH
• Polymorphism, Single-Stranded Conformational MeSH
• Myosin Heavy Chains genetics   MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• kardiologie
• biologie
• NML Publication type
• závěrečné zprávy o řešení grantu IGA MZ ČR

• MeSH
• Gene Amplification MeSH
• Adult MeSH
• Exons MeSH
• Cardiomyopathy, Hypertrophic genetics   pathology   MeSH
• Humans MeSH
• Mutation MeSH
• Cardiac Myosins genetics   MeSH
• Myosin Heavy Chains genetics   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Biopsy MeSH
• Diagnosis, Differential MeSH
• Distal Myopathies * diagnosis   genetics   MeSH
• Child MeSH
• Electromyography MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Muscle Weakness etiology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Electromyography MeSH
• Muscular Dystrophy, Emery-Dreifuss pathology   MeSH

• MeSH
• Adult MeSH
• Humans MeSH
• Arrhythmias, Cardiac etiology   MeSH
• Muscular Dystrophy, Emery-Dreifuss * diagnosis   classification   complications   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Leg MeSH
• Adult MeSH
• Electromyography MeSH
• Middle Aged MeSH
• Humans MeSH
• Shoulder MeSH
• Muscular Dystrophy, Emery-Dreifuss MeSH
• Muscular Dystrophies diagnosis   MeSH
• Syndrome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH

Described here is the phenotypical expression of a novel LMNA mutation c.1157 G>T in a Czech patient with an early-onset form of Emery-Dreifuss muscular dystrophy. The mutation predicts aberrant splicing. Now 21 years old, the patient has had slowly progressing muscle dystrophy since the age of one and early contractures of elbows. He is the only family member affected. Even though the dystrophy typically affects the heart as well, in the present case these signs are not yet expressed.

• MeSH
• Phenotype MeSH
• Lamin Type A genetics   MeSH
• Humans MeSH
• Elbow Joint MeSH
• Lordosis genetics   MeSH
• Mutation, Missense MeSH
• Young Adult MeSH
• DNA Mutational Analysis MeSH
• Scoliosis genetics   MeSH
• Muscular Dystrophy, Emery-Dreifuss genetics   MeSH
• Age of Onset MeSH
• Check Tag
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Publication type
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH