Cardiomyopathy is a group of primary diseases of the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. An irregular heart beat and fainting may occur. Those affected are at an increased risk of sudden cardiac death.
Dwarfism is a condition wherein an organism is exceptionally small, and mostly occurs in the animal kingdom. In humans, it is sometimes defined as an adult height of less than 147 centimetres, regardless of sex; the average adult height among people with dwarfism is 120 centimetres (4 ft). Disproportionate dwarfism is characterized by either short limbs or a short torso. In cases of proportionate dwarfism, both the limbs and torso are unusually small. Intelligence is usually normal, and most have a nearly normal life expectancy. People with dwarfism can usually bear children, though there are additional risks to the mother and child depending upon the underlying condition.
Brugada syndrome (BrS) is a genetic disorder in which the electrical activity of the heart is abnormal due to channelopathy. It increases the risk of abnormal heart rhythms and sudden cardiac death. Those affected may have episodes of syncope. The abnormal heart rhythms seen in those with Brugada syndrome often occur at rest. They may be triggered by a fever.
Genetic counseling is the process of investigating individuals and families affected by or at risk of genetic disorders to help them understand and adapt to the medical, psychological and familial implications of genetic contributions to disease. This field is considered necessary for the implementation of genomic medicine. The process integrates:
Arrhythmogenic cardiomyopathy (ACM), arrhythmogenic right ventricular dysplasia (ARVD), or arrhythmogenic right ventricular cardiomyopathy (ARVC), most commonly is an inherited heart disease.
Hereditary inclusion body myopathies (HIBM) are a group of rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles.
Desmoglein-2 is a protein that in humans is encoded by the DSG2 gene. Desmoglein-2 is highly expressed in epithelial cells and cardiomyocytes. Desmoglein-2 is localized to desmosome structures at regions of cell-cell contact and functions to structurally adhere adjacent cells together. In cardiac muscle, these regions are specialized regions known as intercalated discs. Mutations in desmoglein-2 have been associated with arrhythmogenic right ventricular cardiomyopathy and familial dilated cardiomyopathy.
Ectrodactyly–ectodermal dysplasia–cleft syndrome, or EEC, and also referred to as EEC syndrome and split hand–split foot–ectodermal dysplasia–cleft syndrome is a rare form of ectodermal dysplasia, an autosomal dominant disorder inherited as a genetic trait. EEC is characterized by the triad of ectrodactyly, ectodermal dysplasia, and facial clefts. Other features noted in association with EEC include vesicoureteral reflux, recurrent urinary tract infections, obstruction of the nasolacrimal duct, decreased pigmentation of the hair and skin, missing or abnormal teeth, enamel hypoplasia, absent punctae in the lower eyelids, photophobia, occasional cognitive impairment and kidney anomalies, and conductive hearing loss.
Desmoplakin is a protein in humans that is encoded by the DSP gene. Desmoplakin is a critical component of desmosome structures in cardiac muscle and epidermal cells, which function to maintain the structural integrity at adjacent cell contacts. In cardiac muscle, desmoplakin is localized to intercalated discs which mechanically couple cardiac cells to function in a coordinated syncytial structure. Mutations in desmoplakin have been shown to play a role in dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, where it may present with acute myocardial injury; striate palmoplantar keratoderma, Carvajal syndrome and paraneoplastic pemphigus.
Plakoglobin, also known as junction plakoglobin or gamma-catenin, is a protein that in humans is encoded by the JUP gene. Plakoglobin is a member of the catenin protein family and homologous to β-catenin. Plakoglobin is a cytoplasmic component of desmosomes and adherens junctions structures located within intercalated discs of cardiac muscle that function to anchor sarcomeres and join adjacent cells in cardiac muscle. Mutations in plakoglobin are associated with arrhythmogenic right ventricular dysplasia.
The genetic basis of coat colour in the Labrador Retriever has been found to depend on several distinct genes. The interplay among these genes is used as an example of epistasis.
Ryanodine receptor 2 (RYR2) is one of a class of ryanodine receptors and a protein found primarily in cardiac muscle. In humans, it is encoded by the RYR2 gene. In the process of cardiac calcium-induced calcium release, RYR2 is the major mediator for sarcoplasmic release of stored calcium ions.
Desmocollin-2 is a protein that in humans is encoded by the DSC2 gene. Desmocollin-2 is a cadherin-type protein that functions to link adjacent cells together in specialized regions known as desmosomes. Desmocollin-2 is widely expressed, and is the only desmocollin isoform expressed in cardiac muscle, where it localizes to intercalated discs. Mutations in DSC2 have been causally linked to arrhythmogenic right ventricular cardiomyopathy.
Plakophilin-2 is a protein that in humans is encoded by the PKP2 gene. Plakophilin 2 is expressed in skin and cardiac muscle, where it functions to link cadherins to intermediate filaments in the cytoskeleton. In cardiac muscle, plakophilin-2 is found in desmosome structures located within intercalated discs. Mutations in PKP2 have been shown to be causal in arrhythmogenic right ventricular cardiomyopathy.
Transmembrane protein 43 is a protein that in humans is encoded by the TMEM43 gene. TMEM43 may have an important role in maintaining nuclear envelope structure by organizing protein complexes at the inner nuclear membrane. Required for retaining emerin at the inner nuclear membrane. However, the localization of TMEM43 in myocardial tissue is controversial discussed. Franke et al. demonstrated that TMEM43 is localized at the intercalated disc but not at the nuclear envelope. In contrast Christensen et al. have shown that TMEM43 is mainly localized at the sarcolemma. Mutations in TMEM43 are associated with ARVD and EDMD7.
Heart rhythm disturbances have been seen among astronauts. Most of these have been related to cardiovascular disease, but it is not clear whether this was due to pre-existing conditions or effects of space flight. It is hoped that advanced screening for coronary disease has greatly mitigated this risk. Other heart rhythm problems, such as atrial fibrillation, can develop over time, necessitating periodic screening of crewmembers’ heart rhythms. Beyond these terrestrial heart risks, some concern exists that prolonged exposure to microgravity may lead to heart rhythm disturbances. Although this has not been observed to date, further surveillance is warranted.
Frank I. Marcus was an American cardiologist and Emeritus Professor of Medicine at the University of Arizona Health Sciences Center, the author of more than 290 publications in peer-reviewed medical journals and of 90 book chapters. He was considered a world expert on arrhythmogenic right ventricular cardiomyopathy (ARVC) and was a member of the Editorial/Scientific Board of 14 Cardiovascular Journals as well as a reviewer for 26 other medical publications.
Otodental syndrome, also known as otodental dysplasia, is an exceptionally rare disease that is distinguished by a specific phenotype known as globodontia, that in rare cases can be associated with eye coloboma and high frequency hearing loss. Globodontia is an abnormal condition that can occur in both the primary and secondary dentition, except for the incisors which are normal in shape and size. This is demonstrated by significant enlargement of the canine and molar teeth. The premolars are either reduced in size or are absent. In some cases, the defects affecting the teeth, eye and ear can be either individual or combined. When these conditions are combined with eye coloboma, the condition is also known as oculo-otodental syndrome. The first known case of otodental syndrome was found in Hungary in a mother and her son by Denes and Csiba in 1969. Prevalence is less than 1 out of every 1 million individuals. The cause of otodental syndrome is considered to be genetic. It is an autosomal dominant inheritance and is variable in its expressivity. Haploinsufficiency in the fibroblast growth factor 3 (FGF3) gene (11q13) has been reported in patients with otodental syndrome and is thought to cause the phenotype. Both males and females are equally affected. Individuals diagnosed with otodental syndrome can be of any age; age is not a relevant factor. Currently there are no specific genetic treatments for otodental syndrome. Dental and orthodontic management are the recommended course of action.
Robert Roberts, is a cardiologist, geneticist, academic, and medical researcher.
Nikos Protonotarios was a Greek researcher and cardiologist who made fundamental contributions to the field of arrhythmogenic myocardial diseases.
