Table 2.

Phenocopy Conditions for Hypertrophic Cardiomyopathy

PhenotypeGeneProteinPhenotypic Clue
AMPK-mediated glycogen storagePRKAG2Protein kinase A, γ subunitNormal or reduced left ventricular systolic function, pre-excitation pattern
Pompe diseaseGAAα-1,4-glucosidase (acid maltase)Autosomal recessive, multiorgan disease, pre-excitation pattern
Anderson–Fabry diseaseGLAα-galactosidase AX-linked, multisystem also involving skin, kidney, and peripheral nerves
Danon diseaseLAMP2Lysosome-associated membrane protein 2X-linked dominant, proximal muscle weakness, intellectual disability, short PR on ECG, elevated CK levels
AmyloidosisTTRTransthyretinLow QRS voltage, other organ involvement, subendothelial LGE
Kearns–Sayre syndromemtDNAMitochondrial proteinMultisystem disease
Friedreich ataxiaFRDAFrataxinAutosomal recessive, neurodegeneration
Myotonic dystrophyDMPKMyotonin protein kinaseMyotonia, muscular dystrophy, cataract, and frontal baldness
ZNF9Zinc finger factor 9
Noonan/LEOPARD syndromes (rasopathies)PTPN11Protein tyrosine phosphatase, nonreceptor type 11Congenital heart defects, lentigines, Café-au-lait spots
SOS1 and SOS2Son of sevenless
RAF1Murine leukemia viral oncogene homolog 1
KRASKirsten rat sarcoma virus homolog
Others (A2ML1, BRAF, CBL, MAP2K1, MAP2K2, NRAS, RIT1, RRAS, and SHOC2)
Neimann–Pick diseaseNPC1Neimann–PickAutosomal recessive neurodegenerative disease
Refsum diseasePAHX (PHYH)Phytanoyl-CoA hydroxylaseRetinitis pigmentosa, peripheral neuropathy, and ataxia
DeafnessMYO6Unconventional myosin 6Autosomal dominant deafness
  • CK indicatescreatine kinase; and LGE, late gadolinium enhancement.