Table 2.

The differential diagnosis of HCM and other ‘phenocopies’

Disease		Etiology		Clinical manifestation		Auxiliary examinations
		Pathogenic gene	Inheritance pattern	Cardiac	Extra-cardiac	Electrocardiography	Echocardiography	Cardiac magnetic resonance	Endomyocardial biopsy	Others	Treatment
Hypertrophic cardiomyopathy		MYBPC3, MYH7, TNNT2, TNNI3, MLY2, MYL3, TPM1, ACTC1, etc.	AD	Asymptomatic, or exercise-related symptoms, such as dyspnea, chest pain, palpitation and syncope, SCD, cardiac murmur	No	LV high voltage, T-wave inversion	Asymmetric septal hypertrophy ≥ 15 mm, normal or higher systolic function, varied diastolic dysfunction, reduced LV GLS	LV wall thickness, focal septal LGE, increased native T1 value and ECV	Cardiomyocyte hypertrophy and disarray, interstitial fibrosis, intramural coronary artery abnormalities	No	Beta blocker, cardiac myosin inhibitor, nondihydropyridine CCB, septal reduction therapy, ICD
Athlete's heart		No	No	Asymptomatic	No	Normal	Mild symmetrical LVH (usually ≤ 15 mm), normal systolic or diastolic function	Normal	Normal	No	Withdrawal from exercises
Aortic stenosis		No	No	Dyspnea, chest pain, palpitation and syncope, SCD, cardiac murmur	No	LV high voltage	Mild symmetrical LVH (usually ≤ 15 mm), aortic valve lobe thickened and valve orifice area decreased	Nonspecific	Nonspecific	No	Transcatheter aortic valve replacement, surgical aortic valve replacement
Cardiac amyloidosis	AL	No	No	HF (dyspnea, edema, etc.), arrhythmia, myocardial ischemia, hypotension, syncope, angina	Polyneuropathy, nephropathy, autonomic dysfunction, macroglossia, periorbital purpura, liver involvement	Low QRS voltage and decreased voltage/mass ratio, pseudo-infarction, conduction disturbance	Symmetrical pseudo-hypertrophy involving LV, right ventricle, atrial septum, valves, with speckle sign, mildly systolic dysfunction, severe diastolic dysfunction, decreased LV GLS with apical sparing, pericardial effusion	LV wall thickness, diffuse LGE with subendocardial and transmural patterns, increased native T1 value and ECV	Amyloid deposition, stained with Congo red, ‘apple green’ birefringence on polarized light microscope, interstitial fibrosis, 8–12 nm unbranched structures observed on electron microscopy, amyloid typing using immunohistochemical analysis/mass spectrometry	Serum free light chain (FLC) assay: abnormal κ/λ ratio; serum (SPIE), and urine (UPIE) protein electrophoresis with immunofixation: clonal immunoglobulin and/or clonal light chain	Antiplasma cell therapy, including protein proteasome inhibitor, daratumumab, immunomodulatory drug, autologous stem cell transplantation or cardiac transplantation
	ATTRv	TTR (common genotypes: Val30Met, Val122Ile, Thr60Ala)	AD		Polyneuropathy, orthostatic hypotension, vitreous opacities, gastrointestinal problems					99 mTc-pyrophosphate (PYP): grade 2 or 3 myocardial uptake of radiotracer	Genetic silencer, TTR tetramer stabilizer, TTR disruption/reabsorption, liver transplantation or cardiac transplantation
	ATTRwt	No	No		Carpal tunnel syndrome, lumbar spinal stenosis, ruptures biceps tendon
Fabry disease		GLA	XR	HF, arrhythmia, myocardial ischemia	Angiokeratoma, hypohidrosis, cornea verticillata, gastrointestinal symptoms, neuropathic pain, renal damage, early-onset cerebral infarction, hearing impairment, etc.	Short PR interval without preexcitation, bradycardia	Concentrically LVH with normal systolic function, aortic root dilation, reduced longitudinal strain in the basal inferolateral segment as well as loss of the base-to-apex circumferential strain gradient	Hypertrophy of papillary muscles, mid-layer posterolateral LGE, lower native T1 value	No	No	Enzyme replacement therapy, agalsidase α (Replagal) or agalsidase β (Fabrazyme)
Danon disease		LAMP2	XD	Severe symmetrical LVH (usually > 30mm) or DCM, inherited preexcitation syndrome	Proximal skeletal myopathy and mental retardation	Preexcitation syndrome	Severe symmetrical LVH or DCM, decreased LV GLS with apical sparing	LGE in the anterior, lateral and/or posterior wall of the subendocardium, myocardium or transmural, usually not involved in the middle interventricular septum	Electron microscopy shows intracytoplasmic vacuoles containing autophagic material and glycogen in both skeletal muscle and endomyocardial tissue biopsy	No	No
Pompe disease		GAA	AD	Increased myocardial wall thickness	Skeletal myopathy often presents with progressive muscle weakness	Short PR interval without preexcitation	LV hypertrophy	LV hypertrophy	Electron microscopy of a muscle biopsy indicates vacuolar myopathy with glycogen accumulation in lysosomes and free glycogen in the cytoplasm	No	No
PRKAG2 cardiac syndrome		PRKAG2	AD	Symmetrical LVH (> 15 mm), inherited preexcitation syndrome, conduct disorder, and supraventricular tachycardia	No	Preexcitation syndrome	LV hypertrophy	LV hypertrophy	No	No	No
Friedreich's ataxia		FXN	AR	Increased myocardial wall thickness	No	No	No	No	No	No	No
RASopathies		PTPN11, BRAF, etc.	AD	Left ventricular hypertrophy, pulmonary valve stenosis	Cardio-facio-cutaneous syndrome, retardation of growth	Electrocardiographic conduction defect	LV hypertrophy	LV hypertrophy	Intracytoplasmic vacuoles with osmiophilic ‘medullary corpuscles’	No	No

AD, autosomal dominant; AR, autosomal recessive; CCB, calcium channel blocker; DCM, dilated cardiomyopathy; ECV, extracellular volume; GLS, global longitudinal strain; HF, heart failure; ICD, implantable cardioverter defibrillator; LGE, late gadolinium enhancement; LV, left ventricular; LVH, left ventricular hypertrophy; XD, X-linked dominant; XR, X-linked recessive.