RT Journal Article
SR Electronic
T1 Lamin and the heart
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP 468
OP 479
DO 10.1136/heartjnl-2017-312338
VO 104
IS 6
A1 Gabriella Captur
A1 Eloisa Arbustini
A1 Gisèle Bonne
A1 Petros Syrris
A1 Kevin Mills
A1 Karim Wahbi
A1 Saidi A Mohiddin
A1 William J McKenna
A1 Stephen Pettit
A1 Carolyn Y Ho
A1 Antoine Muchir
A1 Paul Gissen
A1 Perry M Elliott
A1 James C Moon
YR 2018
UL http://heart.bmj.com/content/104/6/468.abstract
AB Lamins A and C are intermediate filament nuclear envelope proteins encoded by the LMNA gene. Mutations in LMNA cause autosomal dominant severe heart disease, accounting for 10% of dilated cardiomyopathy (DCM). Characterised by progressive conduction system disease, arrhythmia and systolic impairment, lamin A/C heart disease is more malignant than other common DCMs due to high event rates even when the left ventricular impairment is mild. It has several phenotypic mimics, but overall it is likely to be an under-recognised cause of DCM. In certain clinical scenarios, particularly familial DCM with early conduction disease, the pretest probability of finding an LMNA mutation may be quite high.Recognising lamin A/C heart disease is important because implantable cardioverter defibrillators need to be implanted early. Promising oral drug therapies are within reach thanks to research into the mitogen-activated protein kinase (MAPK) and affiliated pathways. Personalised heart failure therapy may soon become feasible for LMNA, alongside personalised risk stratification, as variant-related differences in phenotype severity and clinical course are being steadily elucidated.Genotyping and family screening are clinically important both to confirm and to exclude LMNA mutations, but it is the three-pronged integration of such genetic information with functional data from in vivo cardiomyocyte mechanics, and pathological data from microscopy of the nuclear envelope, that is properly reshaping our LMNA knowledge base, one variant at a time. This review explains the biology of lamin A/C heart disease (genetics, structure and function of lamins), clinical presentation (diagnostic pointers, electrocardiographic and imaging features), aspects of screening and management, including current uncertainties, and future directions.