Cardiac Magnetic Resonance characterization of Naxos Disease: Report of 3 Cases

Presenting Author(s)

• 

  Paul Salvador Salvador Morales, MD

  Cardiologist
  Instituto Dante Pazzanese de Cardiologia
  São Paulo, Sao Paulo, Brazil

Primary Author(s)

• 

  Paul Salvador Salvador Morales, MD

  Cardiologist
  Instituto Dante Pazzanese de Cardiologia
  São Paulo, Sao Paulo, Brazil

Co-Author(s)

• 

  Tiago Senra, MD, PhD

  Physician
  Dante Pazzanese Institute of Cardiology
  Sao Paulo, Sao Paulo, Brazil
• 

  Marina R. Cavallari, MD

  Doctor
  Instituto Dante Pazzanese de Cardiologia
  São Paulo, Sao Paulo, Brazil
• 

  Alice Cunha Darzé, MD

  Cardiologist
  Instituto Dante Pazzanese de Cardiologia
  São Paulo, Sao Paulo, Brazil
• 

  Natassia SSC Gomes, MD

  Doctor
  Instituto Dante Pazzanese de Cardiologia
  São Paulo, Sao Paulo, Brazil
• LP

  Luciano G. Possa, MD

  Doctor
  Instituto Dante Pazzanese de Cardiologia, Brazil
• ES

  Eduardo Sassaki, MD

  Doctor
  Instituto Dante Pazzanesse de Cardiologia, Brazil
• EB

  Everton R. Barbosa, MD

  MD
  Instituto Dante Pazzanese de Cardiologia, Brazil
• JC

  João Marcelo Caneschi, MD

  Cardiologist
  Instituto Dante Pazzanese de Cardiologia
  São Paulo, Sao Paulo, Brazil
• MN

  Mariana de Oliveira Nunes, MD

  MD
  Intituto Dante Pazzanese de Cardiologia, Brazil
• CP

  Carlos EE Prazeres, MD

  Doctor
  Instituto Dante Pazzanese de Cardiologia, Brazil
• 

  Amanda Marsiaj Rassi, MD

  Cardiologist
  Instituto Dante Pazzanese de cardiologia
  São Paulo, Sao Paulo, Brazil
• GM

  Gustavo R. Modolo, MD

  Doctor
  Instituto Dante Pazzanese de Cardiologia, Brazil
• 

  Camilla F. Reimberg, MD

  Doctor
  Instituto Dante Pazzanese de Cardiologia
  São Paulo , Sao Paulo, Brazil
• Rd

  Rafael de Castro Hendges, MD, PhD

  Cardiologist
  Instituto Dante Pazzanese de Cardiologia
  São Paulo, Sao Paulo, Brazil
• 

  Antonio Tito 3. Paladino Filho, MD, PhD

  Cardiologist
  Hospital Vila Nova Star, Rede D’or São Paulo-SP
  Sao Paulo, Sao Paulo, Brazil
• 

  Ibraim Masciarelli Pinto, MD, PhD

  Director, Non Invasive Cardiology
  Instituto Dante Pazzanese de Cardiologia
  Sao Paulo, Sao Paulo, Brazil

Description of Clinical Presentation: We present three siblings diagnosed with Naxos disease, a rare autosomal recessive cardiomyopathy associated with plakoglobin (JUP) and desmoplakin (DSP) mutations, characterized by cutaneous and cardiovascular manifestations in young adults.

The index case, a 42-year-old woman, had systemic hypertension under control and reported intermittent palpitations and exertional dyspnea, without syncope. Physical examination revealed no decompensation, and ECG showed sinus rhythm with delta waves in precordial leads. Her younger brothers (32 and 25 years old) also reported occasional palpitations. All siblings presented woolly hair and palmoplantar keratoderma. Holter monitoring demonstrated in the 3 cases infrequent, non-sustained ventricular ectopy. Echocardiography revealed significant biventricular systolic dysfunction in the index case and the youngest brother, while the 32 year old patient showed only mild LV dysfunction.

CMR played a pivotal role in identifying regional wall motion abnormalities, fibrofatty replacement, and late gadolinium enhancement (LGE). Genetic testing in the index case confirmed a heterozygous pathogenic variant in DSP, supporting the diagnosis of desmosomal syndrome.

Diagnostic Techniques and Their Most Important Findings: CMR was performed using 1.5T and 3T Philips Ingenia® scanners, with cine SSFP, T1- and T2-weighted, and LGE sequences. Findings highlighted heterogeneous patterns of ventricular involvement:

- Patient 1 (42 years, female): Biventricular dilation with severe dysfunction (LVEF 29%, RVEF 39%), diffuse epicardial LGE in the entire lateral LV wall, and focal fatty infiltration.
- Patient 2 (32 years, male): Mild biventricular dilation (LVEF 48%, RVEF 30%), regional wall motion abnormalities with small dyskinetic RV outflow areas, diffuse epicardial LGE in the LV lateral wall, focal fatty infiltration in the basal anterolateral segment, and marked LGE in the RV.
- Patient 3 (25 years, male): Predominant RV dilation with severe biventricular dysfunction and multifocal LGE, disproportionate to the degree of LV systolic impairment.

CMR enabled comprehensive morphofunctional and tissue characterization, documenting dilation, contractile abnormalities, and distinct patterns of fibrofatty replacement and fibrosis—findings essential for diagnosing the biventricular desmosomal variant of arrhythmogenic cardiomyopathy.

Learning Points from this Case: CMR provides a unique ability to characterize the phenotypic spectrum of Naxos disease, demonstrating that biventricular involvement and myocardial fibrosis burden varies in severity. The integration of ventricular function, wall motion, fatty infiltration, and LGE distribution is crucial for accurate diagnosis and risk stratification of arrhythmogenic cardiomyopathy with desmosomal involvement.

Patient 1: LV-predominant involvement with dilation, diffuse lateral LV epicardial LGE, and focal fatty infiltration. Patient 2: Biventricular dilation with RV free wall microaneurysms, fatty infiltration, and epicardial LGE. Patient 3: RV-predominant dilation with free wall dyskinesia and basal LV fibrosis. Blue arrow: regional wall motion abnormality. Yellow arrow: fatty infiltration. White arrow: late gadolinium enhancement.