PRIMARY (GENETICALLY DETERMINED) DILATION CARDIOMYOPATHY IN A PATIENT WITH NOVEL MUTATION OF LAMIN GENE: CLINICAL AND MORPHOLOGICAL MANAGEMENT

The primary diagnosis of “dilation cardiomyopathy” is syndromal, and demands clarification of nosological origins. In the article, the specifics of such diagnostics is discussed. Clinical case is provided that illustrates the ways of management, diagnostics and treatment of the essential (primary, genetically determined) dilation cardiomyopathy. Patient of 22 year old with no family history, at the ages 20 and 21 y.o. had cardioembolic strokes. Paroxysmal atrial fibrillation was found, raised creatine kinase levels up to 349-1045 U/L, decreased ejection fraction 17%. Heart failure rapidly progressed. In endomyocardial biopsy there was homogenisation of cardiomyocytes, subendocardial lipomatosis with borderline virus-negative myocarditis. By Senger direct sequencing, the novel variant p.E372 in gene LMNA was found, heterozygous. Implantation of CRT-D was done, and in 4 months — cardiac transplant.

dilation cardiomyopathy, laminopathy, endomyocardial biopsy, myocarditis, stroke, heart transplant

1. Hudson L, Morales A, Mauro AC, et al. Family history of dilated cardiomyopathy among patients with heart failure from the HF-ACTION genetic ancillary study. Clin Transl Sci 2013; 6 (3): 179-83.

2. Jacoby D, McKenna WJ. Genetics of inherited cardiomyopathy. Eur Heart J 2012; 33 (3): 296-304.

3. van Tintelen JP1, Hofstra RM, Katerberg H, et al. High yield of LMNA mutations in patients with dilated cardiomyopathy and/or conduction disease referred to cardiogenetics outpatient clinics. Am Heart J 2007; 154 (6): 1130-9.

4. Blagova OV, Nedostup AV, Kogan ЕА, et al. Clinic and morphological approach to the diagnosis of "idiopathic" arrhythmias and DCM syndrome as a basis for differentiated therapy. Part I (diagnostics). Racional'naja farmakoterapija v kardiologii 2014; 10 (1): 62-72. Russian (Благова О.В., Недоступ А.В., Коган Е.А. и др. Клинико-морфологический подход к диагностике “идиопатических” аритмий и синдрома ДКМП как основа дифференцированной терапии. Часть I (диагностика). Рациональная фармакотерапия в кардиологии 2014; 10 (1): 62-72).

5. Muntoni F, Bonne G, Goldfarb LG, et al. Disease severity in dominant Emery Dreifuss is increased by mutations in both emerin and desmin proteins. Brain 2006; 129 (Pt 5): 1260-8.

6. Bonne G, Mercuri E, Muchir A, et al. Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene. Ann Neurol 2000; 48 (2):170-80.

7. Stoyanov N, Winterfield J, Varma N, Gollob MH. Atrial arrhythmias in the young: early onset atrial arrhythmias preceding a diagnosis of a primary muscular dystrophy. Europace 2014; 16 (12): 1814-20.

8. Maggi L, D'Amico A, Pini A, et al. LMNA-associated myopathies: the Italian experience in a large cohort of patients. Neurology 2014; 83 (18): 1634-44.

9. Taylor MR, Fain PR, Sinagra G, et al. Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. JACC 2003; 41 (5): 771-80.

10. Redondo-Vergé L, Yaou RB, Fernández-Recio M, et al. Cardioembolic stroke prompting diagnosis of LMNA-associated Emery-Dreifuss muscular dystrophy. Muscle Nerve 2011; 44 (4): 587-9.

11. Niebroj-Dobosz I, Marchel M, Madej A, et al. Circulating autoantibodies to troponin I in Emery-Dreifuss muscular dystrophy. Acta Myol 2008; 27: 1-6.

12. Komaki H, Hayashi YK, Tsuburaya R, et al. Inflammatory changes in infantile-onset LMNA-associated myopathy. Neuromuscul Disord 2011; 21 (8): 563-8.

13. Baur X, Witt TN, Pongratz D, et al. [Dominant autosomal humeroperoneal syndrome with early contractures and cardiomyopathy (Emery-Dreifuss syndrome)]. [Article in German]. Klin Wochenschr 1987; 65 (15): 738-45.