MedGen

An autosomal dominant subtype of familial hypertrophic cardiomyopathy caused by mutation(s) in the ACTC1 gene, encoding actin, alpha cardiac muscle 1. [from NCI]

Nonfamilial hypertrophic cardiomyopathy tends to be milder. This form typically begins later in life than familial hypertrophic cardiomyopathy, and affected individuals have a lower risk of serious cardiac events and sudden death than people with the familial form.

While most people with familial hypertrophic cardiomyopathy are symptom-free or have only mild symptoms, this condition can have serious consequences. It can cause abnormal heart rhythms (arrhythmias) that may be life threatening. People with familial hypertrophic cardiomyopathy have an increased risk of sudden death, even if they have no other symptoms of the condition. A small number of affected individuals develop potentially fatal heart failure, which may require heart transplantation.

The symptoms of familial hypertrophic cardiomyopathy are variable, even within the same family. Many affected individuals have no symptoms. Other people with familial hypertrophic cardiomyopathy may experience chest pain; shortness of breath, especially with physical exertion; a sensation of fluttering or pounding in the chest (palpitations); lightheadedness; dizziness; and fainting.

In familial hypertrophic cardiomyopathy, cardiac thickening usually occurs in the interventricular septum, which is the muscular wall that separates the lower left chamber of the heart (the left ventricle) from the lower right chamber (the right ventricle). In some people, thickening of the interventricular septum impedes the flow of oxygen-rich blood from the heart, which may lead to an abnormal heart sound during a heartbeat (heart murmur) and other signs and symptoms of the condition. Other affected individuals do not have physical obstruction of blood flow, but the pumping of blood is less efficient, which can also lead to symptoms of the condition. Familial hypertrophic cardiomyopathy often begins in adolescence or young adulthood, although it can develop at any time throughout life.

Hypertrophic cardiomyopathy is a heart condition characterized by thickening (hypertrophy) of the heart (cardiac) muscle. When multiple members of a family have the condition, it is known as familial hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy also occurs in people with no family history; these cases are considered nonfamilial hypertrophic cardiomyopathy.  [from MedlinePlus Genetics]

Hypertrophic cardiomyopathy is a heart condition characterized by thickening (hypertrophy) of the heart (cardiac) muscle. When multiple members of a family have the condition, it is known as familial hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy also occurs in people with no family history; these cases are considered nonfamilial hypertrophic cardiomyopathy. 

In familial hypertrophic cardiomyopathy, cardiac thickening usually occurs in the interventricular septum, which is the muscular wall that separates the lower left chamber of the heart (the left ventricle) from the lower right chamber (the right ventricle). In some people, thickening of the interventricular septum impedes the flow of oxygen-rich blood from the heart, which may lead to an abnormal heart sound during a heartbeat (heart murmur) and other signs and symptoms of the condition. Other affected individuals do not have physical obstruction of blood flow, but the pumping of blood is less efficient, which can also lead to symptoms of the condition. Familial hypertrophic cardiomyopathy often begins in adolescence or young adulthood, although it can develop at any time throughout life.

The symptoms of familial hypertrophic cardiomyopathy are variable, even within the same family. Many affected individuals have no symptoms. Other people with familial hypertrophic cardiomyopathy may experience chest pain; shortness of breath, especially with physical exertion; a sensation of fluttering or pounding in the chest (palpitations); lightheadedness; dizziness; and fainting.

While most people with familial hypertrophic cardiomyopathy are symptom-free or have only mild symptoms, this condition can have serious consequences. It can cause abnormal heart rhythms (arrhythmias) that may be life threatening. People with familial hypertrophic cardiomyopathy have an increased risk of sudden death, even if they have no other symptoms of the condition. A small number of affected individuals develop potentially fatal heart failure, which may require heart transplantation.

Nonfamilial hypertrophic cardiomyopathy tends to be milder. This form typically begins later in life than familial hypertrophic cardiomyopathy, and affected individuals have a lower risk of serious cardiac events and sudden death than people with the familial form. [from MedlinePlus Genetics]

Familial hypertrophic cardiomyopathy-3 (CMH3) is an autosomal dominant disorder characterized by increased myocardial mass with myocyte and myofibrillar disarray (Thierfelder et al., 1994). For a general phenotypic description and a discussion of genetic heterogeneity of hypertrophic cardiomyopathy, see CMH1 (192600). [from OMIM]

Any hypertrophic cardiomyopathy in which the cause of the disease is a mutation in the MYL2 gene. [from MONDO]

Mutations in the PRKAG2 gene (602743) give rise to a moderate, essentially heart-specific, nonlysosomal glycogenosis with clinical onset typically in late adolescence or in the third decade of life, ventricular pre-excitation predisposing to supraventricular arrhythmias, mild to severe cardiac hypertrophy, enhanced risk of sudden cardiac death in midlife, and autosomal dominant inheritance with full penetrance (summary by Burwinkel et al., 2005). [from OMIM]

Any hypertrophic cardiomyopathy in which the cause of the disease is a mutation in the MYL3 gene. [from MONDO]

Hereditary ventricular hypertrophy (CMH, HCM, ASH, or IHSS) in early stages produces a presystolic gallop due to an atrial heart sound, and EKG changes of ventricular hypertrophy. Progressive ventricular outflow obstruction may cause palpitation associated with arrhythmia, congestive heart failure, and sudden death. Seidman (2000) reviewed studies of hypertrophic cardiomyopathy in man and mouse. Reviews Walsh et al. (2022) reviewed hypertrophic cardiomyopathy phenotypes associated with variation in genes encoding nonsarcomeric proteins. The authors suggested that these genes likely contribute to polygenic risk scores derived from genomewide association studies that could be used to improve risk assessment in patients and family members, and noted that the diverse functions of the proteins highlight novel disease pathways and therapeutic targets for cardiomyopathies. Genetic Heterogeneity of Hypertrophic Cardiomyopathy Additional forms of hypertrophic cardiomyopathy include CMH2 (115195), caused by mutation in the TNNT2 gene (191045) on chromosome 1q32; CMH3 (115196), caused by mutation in the TPM1 gene (191010) on chromosome 15q22; CMH4 (115197), caused by mutation in the MYBPC3 gene (600958) on chromosome 11p11; CMH6 (600858), caused by mutation in the PRKAG2 gene (602743) on chromosome 7q36; CMH7 (613690), caused by mutation in the TNNI3 gene (191044) on chromosome 19q13; CMH8 (608751), caused by mutation in the MYL3 gene (160790) on chromosome 3p21; CMH9 (613765), caused by mutation in the TTN gene (188840) on chromosome 2q31; CMH10 (608758), caused by mutation in the MYL2 gene (160781) on chromosome 12q24; CMH11 (612098), caused by mutation in the ACTC1 gene (102540) on chromosome 15q14; CMH12 (612124), caused by mutation in the CSRP3 gene (600824) on chromosome 11p15; CMH13 (613243), caused by mutation in the TNNC1 gene (191040) on chromosome 3p21; CMH14 (613251), caused by mutation in the MYH6 gene (160710) on chromosome 14q12; CMH15 (613255), caused by mutation in the VCL gene (193065) on chromosome 10q22; CMH16 (613838), caused by mutation in the MYOZ2 gene (605602) on chromosome 4q26; CMH17 (613873), caused by mutation in the JPH2 gene (605267) on chromosome 20q12; CMH18 (613874), caused by mutation in the PLN gene (172405) on chromosome 6q22; CMH20 (613876), caused by mutation in the NEXN gene (613121) on chromosome 1p31; CMH21 (614676), mapped to chromosome 7p12.1-q21; CMH22 (see 615248), caused by mutation in the MYPN gene (608517) on chromosome 10q21; CMH23 (see 612158), caused by mutation in the ACTN2 gene (102573) on chromosome 1q43; CMH24 (see 601493), caused by mutation in the LDB3 gene (605906) on chromosome 10q23; CMH25 (607487), caused by mutation in the TCAP gene (604488) on chromosome 17q12; CMH26 (617047), caused by mutation in the FLNC gene (102565) on chromosome 7q32; CMH27 (618052), caused by mutation in the ALPK3 gene (617608) on chromosome 15q25; CMH28 (619402), caused by mutation in the FHOD3 gene (609691) on chromosome 18q12; and CMH29 (620236), caused by mutation in the KLHL24 gene (611295) on chromosome 3q27. The CMH5 designation was initially assigned to a CMH family showing genetic heterogeneity. Subsequently, affected individuals were found to carry mutations in the MYH7 (CMH1) and/or MYBPC3 (CMH4) genes. Mutations in the CALR3 gene (611414), previously suggested to cause a form of CMH (Chiu et al., 2007) designated CMH19, were convincingly shown not to be a monogenic cause of cardiomyopathy by Verhagen et al. (2018); see 611414.0001. Hypertrophic cardiomyopathy has also been associated with mutation in the gene encoding cardiac myosin light-peptide kinase (MYLK2; see 606566.0001), which resides on chromosome 20q13.3; the gene encoding caveolin-3 (CAV3; see 601253.0013), which maps to chromosome 3p25; and with mutations in genes encoding mitochondrial tRNAs: see mitochondrial tRNA-glycine (MTTG; 590035) and mitochondrial tRNA-isoleucine (MTTI; 590045). [from OMIM]