From OMIMDilated cardiomyopathy (CMD) is characterized by cardiac dilatation and reduced systolic function. CMD is the most frequent form of cardiomyopathy and accounts for more than half of all cardiac transplantations performed in patients between 1 and 10 years of age. A heritable pattern is present in 20 to 30% of cases. Most familial CMD pedigrees show an autosomal dominant pattern of inheritance, usually presenting in the second or third decade of life (summary by Levitas et al., 2010).
Olson and Keating (1996) noted that the causes of CMD include myocarditis, coronary artery disease, systemic diseases, and myocardial toxins; idiopathic dilated cardiomyopathy in which these causes are excluded represents approximately one-half of all cases. Idiopathic dilated cardiomyopathy occurs with a prevalence of about 36.5 per 100,000; it accounts for more than 10,000 deaths in the U.S. annually and is the primary indication for cardiac transplantation.
Seidman and Seidman (2001) reviewed the clinical and genetic heterogeneity of dilated cardiomyopathy.
Dilated cardiomyoopathy-1A (CMD1A) is an autosomal dominant disorder with typical onset between the ages of 30 and 40. In contrast to most other forms of familial CMD, sudden cardiac death may be the first manifestaton even in the absence of systolic dysfunction, owing to malignant arrhythmias such as ventricular tachycardia and fibrillation (summary by Lee et al., 2019).
Genetic Heterogeneity of Dilated Cardiomyopathy
Mutations in many other genes have been found to cause different forms of autosomal dominant dilated cardiomyopathy. These include CMD1C (601493), with or without left ventricular noncompaction, caused by mutation in the LDB3 gene (605906) on 10q23; CMD1D (601494), caused by mutation in the TNNT2 gene (191045) on 1q32; CMD1E (601154), caused by mutation in the SCN5A gene (600163) on 3p22; CMD1G (604145), caused by mutation in the TTN gene (188840) on 2q31; CMD1I (604765), caused by mutation in the DES gene (125660) on 2q35; CMD1J (605362), caused by mutation in the EYA4 gene (603550) on 6q23; CMD1L (606685), caused by mutation in the SGCD gene (601411) on 5q33; CMD1M (607482), caused by mutation in the CSRP3 gene (600824) on 11p15; CMD1O (608569), caused by mutation in the ABCC9 gene (601439) on 12p12; CMD1P (609909), caused by mutation in the PLN gene (172405) on 6q22; CMD1R (613424), caused by mutation in the ACTC gene (102540) on 15q14; CMD1S (613426), caused by mutation in the MYH7 gene (160760) on 14q12; CMD1U (613694), caused by mutation in the PSEN1 gene (104311) on 14q24; CMD1V (613697), caused by mutation in the PSEN2 gene (600759) on 1q42; CMD1W (611407), caused by mutation in the gene encoding metavinculin (VCL; 193065) on 10q22; CMD1X (611615), caused by mutation in the gene encoding fukutin (FKTN; 607440) on 9q31; CMD1Y (611878), caused by mutation in the TPM1 gene (191010) on 15q22; CMD1Z (611879), caused by mutation in the TNNC1 gene (191040) on 3p21; CMD1AA (612158), caused by mutation in the ACTN2 gene (102573) on 1q43; CMD1BB (612877), caused by mutation in the DSG2 gene (125671) on 18q12; CMD1CC (613122), caused by mutation in the NEXN gene (613121) on 1p31; CMD1DD (613172), caused by mutation in the RBM20 gene (613171) on 10q25; CMD1EE (613252), caused by mutation in the MYH6 gene (160710) on 14q12; CMD1FF (613286), caused by mutation in the TNNI3 gene (191044) on 19q13; CMD1GG (613642), caused by mutation in the SDHA gene (600857) on 5p15; CMD1HH (613881), caused by mutation in the BAG3 gene (603883) on 10q26; CMD1II (615184), caused by mutation in the CRYAB gene (123590) on 6q21; CMD1JJ (615235), caused by mutation in the LAMA4 gene (600133) on 6q21; CMD1KK (615248), caused by mutation in the MYPN gene (608517) on 10q21; CMD1LL (615373), caused by mutation in the PRDM16 gene (605557) on 1p36; CMD1MM (see 615396), caused by mutation in the MYBPC3 gene (600958) on 11p11; CMD1NN (615916), caused by mutation in the RAF1 gene (164760) on 3p25; CMD1OO (620247), caused by mutation in the VEZF1 gene (606747) on chromosome 17q22; and CMD1PP (see 617047), caused by mutation in the FLNC gene (102565) on chromosome 7q32.
Several additional loci for autosomal dominant familial dilated cardiomyopathy have been mapped: CMD1B (600884) on 9q13; CMD1H (604288) on 2q14-q22; CMD1K (605582) on 6q12-q16; and CMD1Q (609915) on 7q22.3-q31.1.
Autosomal recessive CMD includes CMD2A (611880), caused by mutation in the TNNI3 gene (191044) on 19q13; CMD2B (614672), caused by mutation in the GATAD1 gene (614518) on 7q21; CMD2C (618189), caused by mutation in the PPCS gene (609853) on 1p34; CMD2D (619371), caused by mutation in the RPL3L gene (617416) on 16p13; CMD2E (619492), caused by mutation in the JPH2 gene (605267) on chromosome 20q13; CMD2F (619747), caused by mutation in the BAG5 gene (603885) on chromosome 14q32; CMD2G (619897), caused by mutation in the LMOD2 gene (608006) on chromosome 7q31; CMD2H (620203), caused by mutation in the GET3 gene (601913) on chromosome 19p13; CMD2I (620462), caused by mutation in the CAP2 gene (618385) on chromosome 6p22; CMD2J (620635), caused by mutation in the FLII gene (600362) on chromosome 17p11; and CMD2K (620894), caused by mutation in the GCOM1 gene (see 614071) on chromosome 15q21.
An X-linked form of CMD (CMD3B; 302045) is caused by mutation in the DMD gene (300377). An X-linked form previously designated CMD3A was found to be the same as Barth syndrome (302060).
Reclassified Forms of CMD
The symbol CMD1F was formerly used for a disorder later found to be the same as desmin-related myopathy (601419).
The symbol CMD1N (see 607487) was previously used for a form of dilated cardiomyopathy reported to be caused by a mutation in the TCAP gene (604488.0003); this variant has been reclassified as a variant of unknown significance.
The symbol CMD1T was previously used for a form of dilated cardiomyopathy reported to be caused by a mutation in the TMPO gene (188380.0001); this variant has been reclassified as a variant of unknown significance.
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