Genetic mutations and left ventricular dysfunction in children with familial Mediterranean fever

Aim of the work

To evaluate subclinical cardiac involvement and ventricular function in children with familial Mediterranean fever (FMF) using speckle-tracking modalities and Doppler tissue imaging (DTI) and to study the association between ventricular dysfunction and genetic mutations.

Patients and methods

Fifty children with FMF with no cardiac symptoms were compared to 50 matched control. Echocardiographic data was recorded, including global longitudinal strain (GLS) and global circumferential strain (GCS) for assessment of the left ventricle systolic function using speckle tracking technique and the (E/E') ratio between early filling velocity (E) and peak early diastolic myocardial lengthening velocity (E'). Genetic mutation testing for M694I, M694V, M680I, E148Q was performed.

Results

Patients' mean age was 10.7 ± 2.6 years, 27 (54 %) were girls, and 52 % had homozygous mutations. M694I (20 %), M694V (18 %), and M680I (16 %) were the most common mutations. Diastolic dysfunction indicators (average E/É) were significant compared to control (p = 0.004). Patients had lower GLSs (p = 0.0001) and GCSs (p < 0.0001). The M680I mutation was associated with increased left ventricular end-diastolic volume (p = 0.005) and average E/E' (p = 0.002). M694I mutation was associated with increased E/E' (p = 0.048), decreased GLS (p = 0.016), and GCS (p = 0.023). The M694V mutation was associated with increased disease severity (p = 0.008). The combination of M680I and V726A mutations was associated with a reduced ejection fraction (p = 0.001).

Conclusion

Children with FMF tend to have subclinical left ventricular diastolic dysfunction. Certain genetic mutations increase the likelihood of systolic ventricular dysfunction.