ABC | Volume 114, Nº2, February 2020

Review Article Romano et al. Myocardial alterations in familial lipodystrophy Arq Bras Cardiol. 2020; 114(2):305-312 Table 1 – Case reports of patients with congenital generalized lipodystrophy Authors/year Findings Seip (1959) 3 patients; one with a systolic murmur. 2 had increased blood pressure and cardiomegaly. Seip (1963) 5 patients, all with cardiomegaly. Choremis (1965) 1 patient: cardiomegaly and arterial hypertension Gold et al. (1967) 2 patients (siblings) with moderate cardiomegaly. Brunzell et al. (1968) Presence of cystic angiomatosis in patients with CGL. Montenovesi et al. (1971) 1 patient with cardiomegaly. Bjorntad et al. (1985) 7 patients, 6 of them with CGL. They had systolic murmur, 3 with left ventricular hypertrophy and 2 with biventricular overload. Rheuban et al. (1986) 4 patients, all with systolic ejection murmur and non-obstructive hypertrophic cardiomyopathy. Klair et al. (1993) 1 patient with progressive hypertrophic cardiomyopathy. Chandalia et al. (1995) 1 patient with 20% obstruction of coronary arteries and presence of atheromatous plaques. Westvik et al. (1996) 8 patients, 7 of them with CGL. Presence of cardiomegaly and one death secondary to congestive heart failure. Bjornstad et al. (1996) 8 patients, 7 of them with CGL. Presence of cardiac hypertrophy. Viegas et al. (2000) 1 patient with hypertension and severe symmetric hypertrophy. CGL: Congenital Generalized Lipodystrophy. Adapted from Rego AR, et al. 16 Source: [Adapted from Rego AR, MAG; Faria, CA; Baracho, MFP; Egito, EST; Mesquita, ET; Brandão Neto, J. Alterações cardiovasculares e metabólicas da lipodistrofia generalizada congênita (síndrome de seip-berardinelli)] body mass. Parameters such as total cholesterol levels and blood pressure were similar in both groups. Individuals with lipodystrophy, however, had low HDL cholesterol levels, high fasting blood glucose levels, three-fold higher circulating triglyceride content, and detection of pericardial adipose tissue by cardiovascular imaging methods (Figure 2). A morphological and functional analysis of the heart of these patients by cardiac magnetic resonance imaging showed an increase in left ventricular mass with a concentric pattern. However, there was no difference between the final systolic and diastolic volume values ​or left ventricular ejection fraction when compared to a control group. 2 Thus, in the first clinical study that controlled variables such as blood pressure levels and age between subjects with lipodystrophy and controls, there was still a LV geometric difference between the groups, although both showed no functional alterations. Table 2 – Genotypic and phenotypic analysis of patients with CGL Genetic alteration Geometrical alteration of the left ventricle Electrocardiographic and/or functional analysis CGL1 (AGPAT2 mutation) 9 patients with normal LV mass. 17 ECGs were assessed, 9 of them with abnormalities. 3 patients with mild hypertrophy. 4 patients with moderate hypertrophy. 3 patients with severe hypertrophy. CGL2 (seipin mutation) 2 patients with normal LV mass. 7 ECGs were assessed, 5 of them with abnormalities. 2 patients with mild hypertrophy. 2 patients with moderate hypertrophy. 4 patients with severe hypertrophy. LMNA (R133L) mutation Normal left ventricular mass. Ejection fraction of 35% and low exercise tolerance. Unknown mutation Normal left ventricular mass with concentric remodeling. ECG: Electrocardiogram; LV: left ventricle. Adapted from Lupsa BC, et al. 1 Source: [Adapted from Lupsa BC, Sachdev V, Lungu AO, Rosing DR, Gorden P. Cardiomyopathy in congenital and acquired generalized lipodystrophy: A clinical assessment.] Sims-Williams et al. 25 reported the case of a 62-year-old patient with dilated cardiomyopathy and symptomatic heart failure whose twin brother had died from heart failure, as well as their father. The grandfather, on the other hand, had suffered an embolic stroke and also had ventricular hypertrophy. The entire family had an LMNA gene mutation. The echocardiographic evaluation of this individual revealed marked dilation and deterioration of the left ventricular systolic function, with an LV ejection fraction of 18%, associated with a thickness increase in the left ventricular posterior wall. There was also reduction in the right ventricular function and bi-atrial dilation. Based on these facts, the authors hypothesized that most of the cardiomyopathies found in this group of patients also have a familial etiology, and part of them, caused directly by LMNA mutations. 25 308