DMD Gene Variants and Cardiac Dysfunction in Young Males With Dystrophinopathies

Correlation of Pathogenic Variants in the DMD Gene With Cardiac Dysfunction in Male Children, Adolescents, and Young Adults With Dystrophinopathies: A Pilot Study

The goal of this observational study is to investigate whether the type, location, and extent of pathogenic variants in the DMD gene are associated with cardiac dysfunction in male children, adolescents, and young adults with dystrophinopathies. The study also evaluates whether cardiac biomarkers and electrocardiographic findings can facilitate the early identification of cardiac involvement. Participants will undergo electrocardiography, blood sampling for cardiac biomarker assessment, and transthoracic echocardiography, with cardiac dysfunction evaluated using ejection fraction (EF) and global longitudinal strain (GLS).

Study Overview

• Status: Recruiting
• Conditions: Becker Muscular Dystrophy; Cardiomyopathy; Duchenne Muscular Dystrophy (DMD)

Detailed Description

Pathogenic variants in the DMD gene lead to a spectrum of clinical phenotypes known as dystrophinopathies, with Duchenne muscular dystrophy and Becker muscular dystrophy representing the most common forms. Beyond progressive skeletal muscle weakness, a substantial proportion of patients have cardiac involvement, often progressing to dilated cardiomyopathy -a major cause of morbidity and the leading cause of mortality in this population. Although cardiac involvement is well recognized in dystrophinopathies, the relationship between specific DMD gene variants and the severity or pattern of cardiac dysfunction has not been fully clarified.

This observational pilot study is designed to investigate the association between the type, location, and extent of pathogenic variants in the DMD gene and cardiac dysfunction in male children, adolescents, and young adults aged 2 to 24 years with genetically confirmed dystrophinopathies. In addition to evaluating genotype-cardiac phenotype associations, the study explores whether cardiac biomarkers, electrocardiographic abnormalities, age, ongoing pharmacological treatment, and lipid-related parameters, including non-HDL cholesterol, are associated with early cardiac involvement.

Participants will undergo a structured clinical and cardiac evaluation, including collection of demographic and clinical data, medical history, pharmacological treatment, and comorbidities. Blood samples will be collected at the baseline assessment for measurement of cardiac biomarkers and lipid-related parameters. Cardiological evaluation will be performed in all participants and will comprise electrocardiography and transthoracic echocardiography. Echocardiographic assessment will include both conventional and deformation-based indices of left ventricular systolic function, including ejection fraction and global longitudinal strain.

By integrating genetic, biochemical, electrocardiographic, and echocardiographic data, this multidimensional approach seeks to improve understanding of genotype-cardiac phenotype associations, facilitate earlier recognition of cardiac involvement, and contribute to more individualized monitoring and clinical management in patients with dystrophinopathies.

• Study Type: Observational
• Enrollment (Estimated): 65

Contacts and Locations

• Study Contact: Name: Ioanna Agathokleous, MD, MSc, PhD(c); Phone Number: +30 2313303534; Email: iagatho@auth.gr

Study Locations

• Greece
  • Thessaloniki, Greece
    • Recruiting
    • AHEPA University Hospital of Thessaloniki
    • Contact: Ioanna Agathokleous, MD, MSc, PhD(c); Phone Number: +302313303534; Email: iagatho@auth.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants with genetically confirmed dystrophinopathies followed at the Neuromuscular Disorders Unit of the 2nd Department of Pediatrics, AHEPA University Hospital, Thessaloniki, Greece.

Description

Inclusion Criteria:

• Male sex
• Age between 2 and 24 years at the time of enrollment
• Genetically confirmed dystrophinopathy with a pathogenic or likely pathogenic variant in the DMD gene
• Genetic confirmation based on at least one validated method, including MLPA, NGS, Sanger sequencing, array-CGH, or qPCR
• Written informed consent from parents or legal guardians and, where applicable, consent from the participant

Exclusion Criteria:

• Absence of a genetically confirmed diagnosis of dystrophinopathy, including:
• diagnosis based solely on muscle biopsy without molecular confirmation of a pathogenic or likely pathogenic DMD gene variant
• absence of a confirmed pathogenic variant in the DMD gene, even if maternal carrier status has been identified, unless repeat genetic testing confirms a pathogenic variant in the participant
• Presence of congenital heart disease or other genetic disorders causing primary cardiomyopathy
• Presence of other neuromuscular disorders
• Female carriers, including both manifesting and asymptomatic carriers
• Comorbidities that may independently affect cardiac function, such as severe arterial hypertension, diabetes mellitus, or chronic kidney disease

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Male participants with genetically confirmed dystrophinopathies; Male children, adolescents, and young adults aged 2 to 24 years with genetically confirmed dystrophinopathies caused by pathogenic or likely pathogenic variants in the DMD gene.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between pathogenic DMD gene variants and left ventricular ejection fraction (EF)	Correlation between the type, location, and extent of pathogenic variants in the DMD gene and left ventricular ejection fraction (%), measured using the Simpson's biplane method by transthoracic echocardiography.	On the day of the baseline assessment
Correlation between pathogenic DMD gene variants and global longitudinal strain (GLS)	Correlation between the type, location, and extent of pathogenic variants in the DMD gene and global longitudinal strain (%), derived from speckle-tracking echocardiography and measured offline from recorded echocardiographic images.	On the day of the baseline assessment
Correlation between pathogenic DMD gene variants and blood levels of high-sensitivity troponin T (hs-TnT)	Correlation between the type, location, and extent of pathogenic variants in the DMD gene and blood levels of high-sensitivity troponin T (pg/mL), measured from venous blood samples.	On the day of the baseline assessment
Correlation between pathogenic DMD gene variants and blood levels of N-terminal pro-brain natriuretic peptide (NT-proBNP)	Correlation between the type, location, and extent of pathogenic variants in the DMD gene and blood levels of N-terminal pro-brain natriuretic peptide (pg/mL), measured from venous blood samples.	On the day of the baseline assessment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of electrocardiographic abnormalities in participants with and without cardiac dysfunction	Frequency (%) of electrocardiographic abnormalities, including rhythm disturbances, conduction abnormalities, and repolarization changes, compared between participants with and without cardiac dysfunction, as assessed by electrocardiography.	On the day of the baseline assessment
Blood levels of high-sensitivity troponin T in participants with and without cardiac dysfunction	Blood levels of high-sensitivity troponin T (hs-TnT), measured in pg/mL from venous blood samples, compared between participants with and without cardiac dysfunction.	On the day of the baseline assessment
Blood levels of NT-proBNP in participants with and without cardiac dysfunction	Blood levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), measured in pg/mL from venous blood samples, compared between participants with and without cardiac dysfunction.	On the day of the baseline assessment
Correlation between age and the presence of cardiac dysfunction	Correlation between age (years) and the presence of cardiac dysfunction, based on echocardiographic criteria.	On the day of the baseline assessment
Ongoing pharmacological treatment in participants with and without cardiac dysfunction	Proportion (%) of participants receiving ongoing pharmacological treatment, compared between participants with and without cardiac dysfunction.	On the day of the baseline assessment
Non-HDL cholesterol levels in participants with and without cardiac dysfunction	Non-HDL cholesterol levels (mg/dL) compared between participants with and without cardiac dysfunction.	On the day of the baseline assessment

Collaborators and Investigators

• Sponsor: Aristotle University Of Thessaloniki
• Collaborators: AHEPA University Hospital
• Investigators: Principal Investigator: Andreas Giannopoulos, Professor of Pediatrics and Pediatric Cardiology, MD, PhD, Aristotle University Of Thessaloniki

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: March 20, 2026
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Global longitudinal strain; Cardiac dysfunction; Duchenne muscular dystrophy; Becker muscular dystrophy; NT-proBNP; Dystrophinopathy; hs-TnT; DMD gene; Non-HDL Cholesterol
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Cardiovascular Diseases; Muscular Diseases; Heart Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cardiomyopathies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: 133/2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No