Dilated Cardiomyopathy
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.