Table 4. Inherited syndromes associated with cardiac disease.

Gene	Protein	Disease	Clinical features	Note
DMD	Large sarcolemmal protein dystrophin.	Duchenne muscular dystrophy	Early-onset DCM with history of muscular dystrophy	X-linked, recessive
				Duchenne: 1:4,000 to 1:6,000 live male births182)
		Becker muscular dystrophy	Milder and later onset age of onset of DCM tends to be later	Becker: 1:18,000 live male births183)
Mitochondria	Supply and regulation of energy metabolism	MERRF syndrome	Myoclonic epilepsy, septal hypertrophy and DCM	Maternal transmission or autosomal dominant
		MELAS syndrome	Mitochondrial encephalopathy	Maternal transmission or autosomal dominant
			Lactic acidosis
			Stroke like episodes
			Heart failure
			Symmetrical LVH
		Kearns-Sayre syndrome	Ophalomoplegia, conduction defects and DCM, heart block	Maternal transmission or autosomal dominant
FRDA/FXN	Frataxin: a mitochondrial protein of iron homeostasis	Friedreich ataxia	Cerebellar ataxia, dysarthria, HCM, diabetes, neurosensory hearing loss, and visual impairment supraventricular tachycardia	Spinocerebellar ataxia
PRKAG2	5'-AMP-activated protein kinase subunit gamma-2	PRKAG2-related cardiomyopathy	Symmetrical nonobstructive hypertrophy, diastolic dysfunction184),185)	Skeletal myopathy
TTR	Transthyretin	Amyloidosis	ECG: pseudo-infarct pattern, low-voltage QRS, conduction abnormalities	Neuropathy, autonomic dysfunction, Carpal tunnel syndrome, renal failure and proteinuria
			Echo: LVH+right ventricular hypertrophy
			MRI: global subendocardial or transmural late enhancement, suboptimal myocardial nulling
LAMP2	Lysosome-associated membrane glycoprotein 2	Danon disease	ECG: high-voltage QRS, preexcitation pattern, short PR interval	Skeletal myopathy, intellectual disability
			Echo: LVH
PTPN11RAF1		Noonan syndrome	ECG: left or extreme right axis deviation	Typical facies, short stature, webbed neck, pectus excavatum/carinatum, developmental delay, bleeding disorders
			Echo: congenital heart defects (mainly pulmonary stenosis and hypertrophic cardiomyopathy)
GLA	Galactosidase Alpha	Fabry disease	ECG: LVH, high-voltage QRS, short PR interval, preexcitation, sinus node dysfunction, conduction abnormalities, atrioventricular block, supraventricular tachyarrhythmia8	Angiokeratoma, cornea verticillata, neuropathic pain, stroke/transient ischemic attack, vertigo, tinnitus, hearing impairment, renal failure and proteinuria, GI symptoms
			Echo: LVH

DCM = dilated cardiomyopathy; ECG = electrocardiography; GI = gastrointestinal; LVH = left ventricular hypertrophy; MELAS = mitochondrial encephalo-myopathy with lactic acidosis and stroke-like episodes; MERRF = myoclonic epilepsy with ragged red fibers; MRI = magnetic resonance imaging.