CMD1G is a form of familial, non-syndromic, isolated, dilated cardiomyopathy characterized by ventricular chamber dilatation, systolic and diastolic dysfunction, and congestive heart failure. Affected individuals may suffer from arrhythmia, dyspnea, fatigue, syncope, and swelling of the legs and feet. The disorder usually has an onset in adulthood and many patients have been found to exhibit symptoms after the age of 40. However, the condition can manifest at any age from infancy to late adulthood. CMD1G accounts for 20% of all cases of familial dilated cardiomyopathy.
Diagnosis of CMD1G is made by first ruling out other causes of dilated cardiomyopathy such as ischemic injury, valvular and congenital heart disease, coronary artery disease etc., and then carrying out genetic analysis of the TTN gene. Patients can be treated with pharmacological agents, pacemakers or defibrillators. In severe cases, cardiac transplantation is required for individuals suffering from heart failure. As a disorder with varied penetrance, prognosis of CMD1G varies even between family members. Regular cardiovascular screening is recommended for asymptomatic carriers of known pathogenic TTN mutations as well as for first-degree relatives of affected individuals.
Al-Shamsi et al. (2016) evaluated 85 patients at a metabolic center in Abu Dhabi that had failed to be diagnosed using conventional methods. Whole Exome Sequencing (WES) helped diagnose 50% of these cases. In one patient from a consanguineous family, WES uncovered variants of unknown significance in the TTN gene, which were confirmed to be pathogenic due to a consistent phenotype, biochemical findings and reported pathogenicity.