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Dilated Cardiomyopathy

May 12, 2017

Disease synonyms

Familial dilated cardiomyopathy, FDC, Cardiomyopathy dilated, CMD, Dilated cardiomyopathy, DCM

Inheritance pattern

Autosomal dominant, autosomal recessive or X-linked manner

Clinical features

Cardiomyopathies are disorders with primary abnormalities in the structure and function of the heart. These disorders are commonly grouped into morphological subtypes which include hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and left ventricular noncompaction cardiomyopathy (LVNC) 1.

Dilated cardiomyopathy is defined by the presence of left ventricular dilatation and resulting contractile dysfunction. Genetic mutations involving genes that encode cytoskeletal, sarcomere, and nuclear envelope proteins, among others, account for up to 35% of dilated cardiomyopathy cases1. Idiopathic dilated cardiomyopathy has become one of the most prevalent inherited cardiomyopathies over the past decades. Genetic screening of first-degree relatives has revealed that 30-50% of the cases have a familial origin 2. The prevalence of DCM is estimated at 1:250 3.

Dilated cardiomyopathy (DCM) may be asymptomatic for a number of years. Presentation usually occurs late in the disease course with any one of the following:

  • Heart failure, characterized by symptoms that include edema, orthopnea, paroxysmal nocturnal dyspnea, fatigue and dyspnea on exertion
  • Arrhythmias and/or conduction system disease symptoms that almost exclusively accompany progressive cardiomyopathy and heart failure
  • Thromboembolic disease, including stroke or systemic embolus, and secondary to left ventricular mural thrombus.

More than 50% of DCM-affected cases are genetically determined, and so far more than 40 genes have been identified affecting proteins of a wide variety of cellular structures that regulate cardiac muscle function, such as the sarcomere, the nuclear envelope, the cytoskeleton, the sarcolemma and the intercellular junction4.

A range of approximately 10-20% of DCM, regardless of family history, has been attributed to pathogenic truncating variants in the TTN gene, encoding for protein tintin4, 5. Titin is the largest-known human protein, highly expressed in the sarcomere of the heart muscle. TTN provides both passive force and elasticity to preserve diastolic and systolic function. Also, titin regulates the assembly and length of the sarcomere. While the role of truncation mutations in DCM is accepted, the pathogenic and prognostic role of missense variants is still debated and under investigation.

One of the most commons genes implicated in familial DCM is LMNA, encoding the intermediate filament proteins lamin A. LMNA mutations account for 6% of familial DCM cases1, 6, 7. LMNA gene mutations may be associated with extracardiac features, including skeletal muscle weakness and contractures in the form of Emery-Dreifuss muscular dystrophy or limb girdle muscular dystrophy type. LMNA mutations can also produce Hutchinson-Guilford progeria syndrome, lipodystrophy, and Charcot-Marie-Tooth syndrome type 2B. Cardiovascular disease with LMNA mutations can be limited to DCM with or without conduction system disease.

Mutations in the sarcomere genes cause both hypertrophic cardiomyopathy (HCM) and DCM. Sarcomere mutations have been identified in 25% of idiopathic DCM cases1 and account for 10% of familial DCM1, 7. The most common sarcomere genes identified in familial DCM are β-myosin heavy chain (MYH7) (~4%)1, 7 and Troponin T (TNNT2) (2.9%)1, 7. Other sarcomere genes identified in familial DCM are α-tropomyosin (TPM1), troponin C (TNNC1), troponin I (TNNI3), cardiac actin (ACTC), and others. Furthermore, an analysis of Becker muscular dystrophy gene mutations has indicated the regions of the dystrophin protein that may be prone to cardiomyopathy7. Additional genes which act as part of calcium regulation and ion channels have been identified as causative of DCM.

Treatment of dilated cardiomyopathy and resulting chronic heart failure includes medications that improve survival, such as angiotensin converting enzyme inhibitors (ACE) and β blockers8, and must be used as a preventive measure. Other interventions include arrhythmia management using device therapy and sudden death prevention. Patients who are refractory to medical therapy might benefit from mechanical circulatory support and heart transplantation. Treatment of preclinical disease and the potential role of stem-cell therapy are being investigated8.

CENTOGENE offers sequencing of the genes in the CentoCardio™ panel (see Table 1).

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance
ABCC9 601439 Cantu syndrome/ Hypertrichotic osteochondrodysplasia; dilated cardiomyopathy-1O AD
ACTA2 102620 Aortic aneurysm, familial thoracic 6; Multisystemic smooth muscle dysfunction syndrome; Moyamoya disease 5 AD
ACTC1 102540 familial hypertrophic cardiomyopathy 11; Atrial septal defect 5; dilated cardiomyopathy-1R AD
ACTN2 102573 dilated cardiomyopathy-1AA AD
ACVR2B 602730 Heterotaxy, visceral, 4, autosomal
ACVRL1 601284 Telangiectasia, hereditary hemorrhagic, type 2 AD
AKAP9 604001 long QT syndrome 11 AD
ANK2 106410 long QT syndrome-4 AD
ANKRD1 609599
ARHGAP31 610911 Adams-Oliver syndrome 1 AD
ATM 607585 familial breast-ovarian cancer type 2; ataxia-telangiectasia AD, AR
B3GAT3 606374 Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects AR
BAG3 603883 Myopathy, myofibrillar, 6; dilated cardiomyopathy-1HH AD
BCOR 300485 Microphthalmia, syndromic 2 XLD
BMPR2 600799 Pulmonary hypertension, familial primary, 1, with or without HHT AD
BRAF 164757 Cardiofaciocutaneous Syndrome 1; Lung Cancer; Noonan syndrome 7; LEOPARD syndrome 3 AD
CACNA1C 114205 Timothy syndrome; Brugada syndrome 3; Long QT syndrome 8 AD
CACNB2 600003 Brugada syndrome 4
CALM1 114180 Ventricular tachycardia, catecholaminergic polymorphic, 4; Long QT syndrome 14 AD
CALM2 114182 Long QT syndrome 15 AD
CASQ2 114251 Ventricular tachycardia, catecholaminergic polymorphic, 2 AR
CAV3 601253 Creatine phosphokinase, elevated serum; familial hypertrophic cardiomyopathy 1; Rippling muscle disease; Rippling muscle disease 2; long QT syndrome 9 AD, DiD
CAVIN4 617714
CBL 165360 Leukemia, juvenile myelomonocytic; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia AD
CDH2 114020 AD
CFAP53 614759 Heterotaxy, visceral, 6, autosomal recessive AR
CFC1 605194 Heterotaxy, visceral, 2, autosomal AD
CHD7 608892 CHARGE syndrome; hypogonadotropic hypogonadism-5 with or without anosmia AD
CITED2 602937 Atrial septal defect 8 AD
CLDN16 603959 renal hypomagnesemia type 3 AR
CLDN19 610036 Hypomagnesemia 5, renal, with ocular involvement AR
CNNM2 607803 Hypomagnesemia 6, renal; hypomagnesemia, seizures, and mental retardation type 1 AD, AR
COL1A1 120150 Caffey disease; Ehlers-Danlos syndrome arthrochalasia type 1; osteogenesis imperfecta type 1; osteogenesis imperfecta type 2; osteogenesis imperfecta type 4; OSTEOPOROSIS; osteogenesis imperfecta type 3 AD
COL1A2 120160 osteogenesis imperfecta type 2; osteogenesis imperfecta type 4; OSTEOPOROSIS; Ehlers-Danlos syndrome, cardiac valvular form; osteogenesis imperfecta type 3; Ehlers-Danlos syndrome arthrochalasia type 2 AD, AR
COL3A1 120180 vascular-type Ehlers-Danlos syndrome AD, AR
COL4A1 120130 porencephaly 1; Brain small vessel disease with or without ocular anomalies; Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps; Hemorrhage, intracerebral, susceptibility to AD
COL4A2 120090 Brain small vessel disease type 2; Hemorrhage, intracerebral, susceptibility to AD
COL5A1 120215 Ehlers-Danlos syndrome classic type 1 AD
COL5A2 120190 Ehlers-Danlos syndrome classic type 2 AD
CREBBP 600140 Rubinstein-Taybi syndrome 1 AD
CRELD1 607170 Atrioventricular septal defect, partial, with heterotaxy syndrome AD
CRYAB 123590 Myopathy, myofibrillar, 2; Cataract 16, multiple types; Myopathy, Myofibrillar, Fatal Infantile Hypertonic, Alpha-B Crystallin-Related; dilated cardiomyopathy-1II AD, AR
CSRP3 600824 dilated cardiomyopathy-1M; Cardiomyopathy, familial hypertrophic, 12 AD
CTNNA3 607667 familial arrhythmogenic right ventricular dysplasia type 13 AD
DES 125660 Scapuloperoneal syndrome, neurogenic, Kaeser type; Myopathy, myofibrillar, 1; dilated cardiomyopathy-1I AD, AR
DMD 300377 Becker muscular dystrophy; dilated cardiomyopathy type 3B; Duchenne muscular dystrophy XL, XLR
DNAJC19 608977 3-methylglutaconic aciduria, type 5 AR
DOLK 610746 congenital disorder of glycosylation type 1m AR
DSC2 125645 Arrhythmogenic right ventricular dysplasia 11 AD, AR
DSG2 125671 Arrhythmogenic right ventricular dysplasia 10; dilated cardiomyopathy AD
DSP 125647 dilated cardiomyopathy with woolly hair and keratoderma; arrhythmogenic right ventricular dysplasia type 8; lethal acantholytic epidermolysis bullosa; Keratosis palmoplantaris striata II; dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis AD, AR
DTNA 601239 Left ventricular noncompaction 1, with or without congenital heart defects AD
EFEMP2 604633 Cutis laxa, autosomal recessive, type IB AR
EGF 131530 Hypomagnesemia 4, renal
EHMT1 607001 Kleefstra syndrome AD
ELN 130160 Cutis laxa, autosomal dominant 1, ADCL1; Supravalvar aortic stenosis AD
EMD 300384 Emery-Dreifuss muscular dystrophy type 1 XLR
ENG 131195 hereditary hemorrhagic telangiectasia type 1 AD
EP300 602700 colorectal cancer; Rubinstein-Taybi syndrome 2 AD
EVC 604831 Weyers acrofacial dysostosis; Ellis-van Creveld syndrome AD, AR
EVC2 607261 Weyers acrofacial dysostosis; Ellis-van Creveld syndrome AD, AR
EYA4 603550 Deafness, autosomal dominant 10; dilated cardiomyopathy-1J AD
FBN1 134797 Marfan syndrome; stiff skin syndrome; Weill-Marchesani syndrome 2; geleophysic dysplasia 2; Marfan lipodystrophy syndrome AD
FBN2 612570 congenital contractural arachnodactyly; early-onset macular degeneration AD
FHL1 300163 Scapuloperoneal myopathy, X-linked dominant; Myopathy, X-linked, with postural muscle atrophy; Emery-Dreifuss muscular dystrophy 6; Myopathy, Reducing Body, X-Linked, Early-Onset, Severe; Myopathy, reducing body, X-linked, childhood-onset XL, XLD, XLR
FKTN 607440 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A4; congenital limb-girdle muscular dystrophy-dystroglycanopathy type C4; dilated cardiomyopathy type 1X; congenital muscular dystrophy-dystroglycanopathy without mental retardation type B4 AR
FLNA 300017 Congenital short bowel syndrome; Heterotopia, periventricular / X-linked periventricular heterotopia; Terminal osseous dysplasia; FG syndrome 2; Otopalatodigital syndrome, type II; Frontometaphyseal dysplasia; Melnick-Needles syndrome; otopalatodigital syndrome type I; Cardiac valvular dysplasia, X-linked XL, XLD, XLR
FLNC 102565 Myopathy, myofibrillar, 5; distal myopathy type 4; Cardiomyopathy, Familial Hypertrophic, 26 AD
FOXC1 601090 Iridogoniodysgenesis, type 1; Axenfeld-Rieger syndrome, type 3 AD
FOXF1 601089 Pulmonary hypertension, familial persistent, of the newborn AD
FOXH1 603621
FXYD2 601814 Hypomagnesemia-2, renal AD
GAA 606800 Pompe disease AR
GATA4 600576 Tetralogy of Fallot; Atrial septal defect 2; Ventricular septal defect 1; Atrioventricular septal defect 4 AD
GATA5 611496 Congenital heart defects, multiple types, 5 AD, AR
GATA6 601656 Tetralogy of Fallot; Conotruncal Heart Malformations; Pancreatic agenesis and congenital heart defects; Atrioventricular septal defect 5; Atrial septal defect 9 AD
GDF1 602880 Right atrial isomerism; Transposition of the great arteries, dextro-looped 3 AD, AR
GDF2 605120 Telangiectasia, hereditary, hemorragic, type 5 AD
GJA1 121014 Oculodentodigital dysplasia AD, AR
GJA5 121013 AD
GLA 300644 Fabry disease; Fabry disease, atypical cardiac variant XL
GPC3 300037 Wilms tumor, type 1; Simpson-Golabi-Behmel syndrome, type 1 XLR
GPD1L 611778 Brugada syndrome 2
HCCS 300056 Microphthalmia, syndromic 7 XLD
HCN4 605206 Sick sinus syndrome 2; Brugada syndrome 8 AD
HFE 613609 Alzheimer Disease; hepatoerythropoietic porphyria; variegate porphyria; hemochromatosis type 1; susceptibility to microvascular complications of diabetes type 7; Transferrin serum level QTL2 AD, AR
HRAS 190020 Bladder Cancer; Melanocytic nevus syndrome, congenital, somatic; Nevus, Epidermal; Schimmelpenning-Feuerstein-Mims Syndrome; Thyroid Carcinoma, Follicular; Costello syndrome AD
HTRA1 602194 Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy type 2 AD, AR
ILK 602366
JAG1 601920 Alagille syndrome; Tetralogy of Fallot AD
JPH2 605267 Cardiomyopathy, familial hypertrophic 17 AD
JUP 173325 Naxos disease; Arrhythmogenic right ventricular dysplasia 12 AD, AR
KCNA1 176260 Episodic ataxia/myokymia syndrome AD
KCNA5 176267 Atrial fibrillation, familial, 7 AD
KCND3 605411 spinocerebellar ataxia 19 AD
KCNE1 176261 Jervell and Lange-Nielsen syndrome 2; long QT syndrome 5 AD, AR
KCNE2 603796 long QT syndrome 6 AD
KCNE3 604433 Brugada syndrome 6
KCNH2 152427 long QT syndrome 2 AD
KCNJ2 600681 Andersen Cardiodysrhythmic Periodic Paralysis; Short Qt Syndrome 3; Atrial fibrillation, familial, 9 AD
KCNJ5 600734 Long QT syndrome 13 AD
KCNK3 603220 primary pulmonary hypertension AD
KCNQ1 607542 long QT syndrome-1; Jervell and Lange-Nielsen syndrome; Atrial fibrillation, familial, 3; Short QT syndrome-2 AD, AR
KDM6A 300128 Kabuki syndrome 2 XLD
KMT2D 602113 Kabuki syndrome 1 AD
KRAS 190070 Arteriovenous malformations of the brain; Bladder Cancer; familial breast-ovarian cancer type 2; Gastric Cancer, Hereditary Diffuse; Schimmelpenning-Feuerstein-Mims Syndrome; Lung Cancer; Pancreatic Cancer; acute myeloid leukemia; Noonan syndrome 3; Autoimmune lymphoproliferative syndrome type IV; Cardiofaciocutaneous syndrome 2 AD
LAMA4 600133 dilated cardiomyopathy-1JJ AD
LAMP2 309060 Danon disease XLD
LDB3 605906 dilated cardiomyopathy-1C; Myopathy, myofibrillar, 4 AD
LMNA 150330 dilated cardiomyopathy-1A; Lipodystrophy, familial partial, 2; Hutchinson-Gilford progeria; limb-girdle muscular dystrophy type 1B; Emery-Dreifuss muscular dystrophy 2; Malouf syndrome; Mandibuloacral dysplasia; Restrictive dermopathy, lethal; type 2B1 Charcot-Marie-Tooth disease; Heart-hand syndrome, Slovenian type; Muscular dystrophy, congenital; Emery-Dreifuss muscular dystrophy 3, AR AD, AR
LZTR1 600574 Noonan syndrome type 2; SCHWANNOMATOSIS 2; Noonan syndrome 10 AD, AR
MAP2K2 601263 Cardiofaciocutaneous syndrome 4 AD
MED12 300188 Opitz-Kaveggia syndrome /FG syndrome-1; Lujan-Fryns syndrome XLR
MED13L 608771 Mental retardation and distinctive facial features with or without cardiac defects AD
MEIS2 601740 Cleft palate, cardiac defects, and mental retardation AD
MFAP5 601103 AD
MIB1 608677 Left ventricular noncompaction 7 AD
MMP21 608416 Heterotaxy, visceral, 7, autosomal AR
MMP3 185250 Coronary heart disease, susceptibility to, 6
MYBPC3 600958 familial hypertrophic cardiomyopathy 4; dilated cardiomyopathy-1MM AD, AR
MYH11 160745 familial thoracic aortic aneurysm 4 AD
MYH6 160710 Cardiomyopathy, familial hypertrophic, 14; dilated cardiomyopathy-1EE; Atrial septal defect 3 AD
MYH7 160760 Liang distal myopathy; Scapuloperoneal syndrome, myopathic type; familial hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myopathy, myosin storage, autosomal dominant; dilated cardiomyopathy-1S AD, AR, DiD
MYL2 160781 Cardiomyopathy, familial hypertrophic, 10 AD
MYL3 160790 familial hypertrophic cardiomyopathy 8 AD, AR
MYLK 600922 Aortic aneurysm, familial thoracic 7 AD, AR
MYLK2 606566 familial hypertrophic cardiomyopathy 1 AD, DiD
MYO6 600970 deafness type 37 AD, AR
MYOZ2 605602 Cardiomyopathy, familial hypertrophic, 16 AD
MYPN 608517 dilated cardiomyopathy-1KK; Autosomal recessive Nemaline myopathy type 11 AD, AR
NEBL 605491
NEXN 613121 dilated cardiomyopathy-1CC; familial hypertrophic cardiomyopathy 20 AD
NF1 613113 neurofibromatosis type 1; Neurofibromatosis-Noonan syndrome; Leukemia, juvenile myelomonocytic AD
NIPBL 608667 Cornelia de Lange syndrome 1 AD
NKX2-5 600584 Atrial Septal Defect 7 With Or Without Atrioventricular Conduction Defects; Tetralogy of Fallot; Conotruncal Heart Malformations; Hypothyroidism, Congenital, Nongoitrous, 5; Ventricular septal defect 3; Hypoplastic left heart syndrome 2 AD
NKX2-6 611770 Conotruncal Heart Malformations
NODAL 601265 Heterotaxy, visceral, 5, autosomal AD
NOTCH1 190198 aortic valve disease type 1; Adams-Oliver syndrome 5 AD
NOTCH2 600275 Hajdu-Cheney syndrome; Alagille syndrome 2 AD
NOTCH3 600276 CADASIL; Lateral meningocele syndrome AD
NPPA 108780 Atrial standstill 2 AD, AR
NR2F2 107773 Congenital heart defects, multiple types, 4 AD
NRAS 164790 colorectal cancer; Melanocytic nevus syndrome, congenital, somatic; Nevus, Epidermal; Schimmelpenning-Feuerstein-Mims Syndrome; Thyroid Carcinoma, Follicular; Neurocutaneous melanosis, somatic; Noonan syndrome 6; Autoimmune lymphoproliferative syndrome type IV AD
NSD1 606681 Sotos syndrome 1 AD
PDLIM3 605889
PKD1L1 609721 Visceral heterotaxy type 8 AR
PKD2 173910 polycystic kidney disease type 2 AD
PKP2 602861 arrrhythmogenic right ventricular dysplasia 9 AD
PLN 172405 dilated cardiomyopathy-1P; Cardiomyopathy, familial hypertrophic, 18 AD
PRDM16 605557 left ventricular noncompaction 8 AD
PRKAG2 602743 Wolff-Parkinson-White syndrome; fatal congenital hypertrophic cardiomyopathy due to glycogen storage disease; familial hypertrophic cardiomyopathy 6 AD
PRKG1 176894 familial thoracic aortic aneurysm type 8 AD
PSEN1 104311 Pick disease; Dementia, frontotemporal; early-onset familial Alzheimer disease-3; dilated cardiomyopathy-1U; Acne inversa, familial, 3 AD
PSEN2 600759 Alzheimer disease, type 4; dilated cardiomyopathy-1V AD
PTPN11 176876 LEOPARD syndrome 1; Noonan syndrome 1; Leukemia, juvenile myelomonocytic AD
RAF1 164760 Noonan syndrome 5; Cardiomyopathy, dilated, 1NN AD
RASA1 139150 Capillary malformation-arteriovenous malformation AD
RBM10 300080 TARP syndrome XLR
RBM20 613171 dilated cardiomyopathy-1DD AD
RIT1 609591 Noonan syndrome 8 AD
RYR2 180902 Arrhythmogenic right ventricular dysplasia 2; Ventricular tachycardia, catecholaminergic polymorphic, 1 AD
SALL1 602218 Townes-Brocks syndrome AD
SALL4 607343 Okihiro syndrome AD
SCN10A 604427 familial episodic pain syndrome, 2 AD
SCN1B 600235 generalized epilepsy with febrile seizures plus-1; Brugada syndrome 5; Epileptic encephalopathy, early infantile, 52 AD, AR
SCN2B 601327 AD
SCN3B 608214 Brugada syndrome 7 AD
SCN4B 608256 Long Qt Syndrome 10 AD
SCN5A 600163 susceptibility to sudden infant death syndrome; Brugada syndrome 1; dilated cardiomyopathy-1E; long QT syndrome 3; Sick sinus syndrome 1; Familial atrial fibrillation type 10 AD, AR
SCO2 604272 Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1; Myopia 6 AD, AR
SDHA 600857 mitochondrial complex II deficiency; Leigh syndrome; dilated cardiomyopathy-1GG; paragangliomas type 5 AD, AR, M
SEMA3A 603961 hypogonadotropic hypogonadism 16 with or without anosmia AD
SGCD 601411 limb-girdle muscular dystrophy type 2F; dilated cardiomyopathy-1L AR
SHOC2 602775 Noonan Syndrome-Like Disorder With Loose Anagen Hair AD
SKI 164780 Shprintzen-Goldberg Craniosynostosis Syndrome AD
SLC12A3 600968 Gitelman syndrome AR
SLC22A5 603377 systemic primary carnitine deficiency AR
SLC25A4 103220 Progressive External Ophthalmoplegia With Mitochondrial Dna Deletions, Autosomal Dominant, 2; mitochondrial DNA depletion syndrome 12; mitochondrial DNA depletion syndrome type 12A AD, AR
SLC2A10 606145 arterial tortuosity syndrome AR
SLMAP 602701
SMAD3 603109 Loeys-Dietz syndrome 3 AD
SMAD4 600993 Myhre syndrome; Juvenile polyposis syndrome, infantile form; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; Pancreatic Cancer AD
SMAD6 602931 Aortic valve disease 2; Craniosynostosis type 7 AD
SMC3 606062 Cornelia de Lange syndrome 3 AD
SNTA1 601017 long QT syndrome 12 AD
SOS1 182530 Noonan syndrome 4 AD
SOS2 601247 Noonan syndrome type 9 AD
SOX2 184429 Microphthalmia, Syndromic 3 AD
STRA6 610745 Microphthalmia, isolated, with coloboma 8 AR
SYNE1 608441 autosomal recessive spinocerebellar ataxia 8; Emery-Dreifuss muscular dystrophy 4 AD, AR
SYNE2 608442 Emery-Dreifuss muscular dystrophy 5 AD
TAB2 605101 Congenital heart defects, nonsyndromic, 2 AD
TAZ 300394 Barth syndrome XLR
TBX1 602054 Tetralogy of Fallot; DiGeorge syndrome; Velocardiofacial syndrome; Conotruncal Heart Malformations AD
TBX20 606061 Atrial septal defect 4
TBX5 601620 Holt-Oram syndrome AD
TCAP 604488 limb-girdle muscular dystrophy type 2G; cardiomyopathy, familial hypertrophic, 25 AD, AR
TFAP2B 601601 Char syndrome; Patent ductus arteriosus 2 AD
TGFB2 190220 Loeys-Dietz syndrome 4 AD
TGFB3 190230 Arrhythmogenic right ventricular dysplasia 1; Loeys-Dietz syndrome 5 AD
TGFBR1 190181 Multiple Self-Healing Squamous Epithelioma, Susceptibility To; Loeys-Dietz syndrome 1 AD
TGFBR2 190182 Esophageal cancer, somatic; Loeys-Dietz syndrome 2; Colorectal cancer, hereditary nonpolyposis, type 6 AD
TLL1 606742 Atrial septal defect 6 AD
TMEM43 612048 arrhythmogenic right ventricular dysplasia 5 AD
TNNC1 191040 dilated cardiomyopathy-1Z; familial hypertrophic cardiomyopathy 13 AD
TNNI3 191044 Cardiomyopathy, familial restrictive, 1; dilated cardiomyopathy-2A; familial hypertrophic cardiomyopathy 7 AD, AR
TNNT2 191045 familial hypertrophic cardiomyopathy 2; dilated cardiomyopathy-1D AD
TPM1 191010 Cardiomyopathy, familial hypertrophic, 3; dilated cardiomyopathy-1Y AD
TRDN 603283 catecholaminergic polymorphic ventricular tachycardia type 5 AR
TREX1 606609 systemic lupus erythematosus; retinal vasculopathy with cerebral leukodystrophy; Aicardi-Goutieres syndrome type 1; chilblain lupus type 1 AD, AR
TRIM63 606131
TRPM4 606936 AD
TRPM6 607009 Hypomagnesemia 1, intestinal AR
TTN 188840 Tibial muscular dystrophy, tardive; Hereditary myopathy with early respiratory failure; dilated cardiomyopathy type 1G; limb-girdle muscular dystrophy type 2J; early-onset myopathy with fatal cardiomyopathy; familial hypertrophic cardiomyopathy type 9 AD, AR
TTR 176300 familial transthyretin amyloidosis AD
VCL 193065 dilated cardiomyopathy-1W; Cardiomyopathy, familial hypertrophic, 15 AD
ZEB2 605802 Mowat-Wilson syndrome AD
ZFPM2 603693 Tetralogy of Fallot; Diaphragmatic hernia 3; 46XY sex reversal 9 AD
ZIC3 300265 Heterotaxy, visceral, 1, x-linked; Vacterl association, x-linked, with or without hydrocephalus XLR

Differential diagnosis

The differential diagnosis of dilated cardiomyopathy related disorders – depending on the major symptoms in the initial case – includes the following diseases1:

  • HFE-associated hereditary hemochromatosis
  • Emery-Dreifuss muscular dystrophy
  • Limb girdle muscular dystrophy 1B
  • Laing distal myopathy
  • Carvajal syndrome
  • Becker muscular dystrophy (late onset of dilated cardiomyopathy)
  • Barth syndrome

Testing strategy

CENTOGENE offers advanced, fast and cost-effective strategy to test large NGS panels and diagnose complex phenotypes based on the PCR-free Whole Genome Sequencing and NGS technology. This approach offers an unparalleled advantage by reducing amplification/capture biases and provides sequencing of entire gene at a more uniform coverage.

To confirm/establish the diagnosis, CENTOGENE offers the following testing strategy for dilated cardiomyopathy NGS Panel Genomic targeted towards this specific phenotype:

Step 1: Whole genome sequencing from a single filter card. The sequencing covers the entire genic region (coding region, exon/intron boundaries, intronic and promoter) for all the genes included in the Cardiomyopathy dilated panel. Copy Number Variants analysis derived from NGS data is also included.

Step 2: If no mutation is identified after analysis of the Cardiomyopathy dilated panel, based on the approval and consent, we further recommend to continue the bioinformatics analysis of the data obtained by whole genome sequencing to cover genes that are either implicated in an overlapping phenotype or could be involved in a similar pathway but not strongly clinically implicated based on the current information in literature.

Referral reasons

The following individuals are candidates for dilated cardiomyopathy panel genetic testing:

  • Individuals with a family history of disease and presentation of the most common symptoms
  • Individuals without a positive family history, but with symptoms resembling this disease
  • Individuals with a negative but suspected family history, in order to perform proper genetic counseling (prenatal analyses are recommended in families with affected individuals).

Test utility

Sequencing, deletion/duplication of this gene and related genes should be performed in all individuals suspected for this particular phenotype. In parallel, other genes reported to be related with this clinical phenotype should also be analyzed for the presence of mutations, due to the overlap in many clinical features caused by those particular genes.

Confirmation of a clinical diagnosis through genetic testing can allow for genetic counseling and may direct medical management. Genetic counseling can provide a patient and/or family with the natural history of the condition, identify at-risk family members, provide reproductive risks as well as preconception/prenatal options, and allow for appropriate referral for patient support and/or resources.