The MOGE(S) Classification for a Phenotype–Genotype Nomenclature of Cardiomyopathy: Endorsed by the World Heart Federation

The authors of the paper, endorsed by the World Heart Federation, propose a new classification for Cardiomyopathies based on the current knowledge on phenotype-genotype correlation. A 5 letter scheme called MOGE(S), similar to the TNM classification in oncology, is described in an attempt for standardization. Current classifications (AHA and ESC) have their limitations to appropriately address a constantly changing scenario with increasing sophistication.

The term “idiopathic cardiomyopathy” as a cardiomyopathy of unknown etiology is no-longer appropriate, as the cause of the disease, often genetic, and the mechanisms are partly identified in an increasing proportion of cardiomyopathies.

The field is gaining complexity. There is a significant genetic heterogeneity which is expected to increase with the recently implemented massive sequencing techniques. It is conceivable that although the diagnosis based on phenotype is still clinically useful, it is not sufficient to stratify prognosis in cardiomyopathies caused by mutations in different genes and that grouping cardiomyopathies per disease gene provides the basis for implementation of disease-specific research.

There is enough information in the literature to conclude that mutations in some genes causing Dilated Cardiomyopathy are associated to a particularly poor prognosis and in which indication of ICDs should be considered in early phases of the disease when systolic impairment is only mild or moderate. Based on the underlying gene mutations, numerous new terms such as: cardiodystrophinopathies, desminopathies, laminopathies, RASopathies, etc. have been proposed. Interestingly, mutations in the same genes, like MYBPC3 are associated with different phenotypes such as Hypertrophic, Dilated and Restrictive Cardiomyopathy.

The new classification aims to include all forms of cardiomyopathies including asymptomatic carriers, early forms and overlapping phenotypes. An extension of the MOGE(S) nomenclature to incorporate channelopathies is considered as possible in the future.

Cardiomyopathies, in this experts document, are described as disorders characterized by morphologically and functionally abnormal myocardium in the absence of any other disease that is sufficient, by itself, to cause the observed phenotype.

Under the “M” the morphofunctional phenotype is recorded: MD= dilated, MH= hypertrophic, MA= arrhythmogenic right ventricular, MR= restrictive and MLVNC= left ventricular non-compaction Cardiomyopathy. Mixed phenotypes are possible (MH+D), remarkable clinical features like AV-block, WPW, raised CK or the presence of epsilon waves (MD[WPW],  MH[WPW] MD[sCK] or MA[epsilon]), asymptomatic non-affected carriers (M0) and early forms (ME[H]) are also included in the notation.

Under the “O” the organ involvement is recorded. OH when the Heart is involved, OM for skeletal muscle involvement, with OK for Kidney, OL for liver, OMR for mental retardation, OO for ocular system, etc. All combinations are possible. 

Under the “G” the genetic pattern of inheritance is recorded. GAD for autosomal dominant, GXL for X-linked, GS for sporadic cases, GU unknown and G0 when family has not been  investigated.

Under the “E” etiological cause is recorded. EG-MYH7[p.Arg403Glu] in the case of cardiomyopathy genetic cause by a mutation in MYH7 gene in position Arg403Glu. Obligate carriers and non-carriers have also an specific notation in this system (EG-OC and EG-neg). Myocarditis is also a recognized cause (EM) with the option of including the suspected causative virus (EV-EBV if Ebstein-Barr virus), other options EM-sarcoidosis for cardiac sarcoidosis or EA-K for kappa AL amyloidosis.

Under the last letter “S” heart failure state (A to D) and or NYHA class is optionally included, which may come in handy for the description of early cardiomyopathy.

The MOGE(S) classification similarly as the TNM is dynamic and patients are coded differently as they develop the disease or after additional information arises from the examinations. A web application for MOGE(S) nomenclature is available at http://moges.biomeris.com