ABC | Volume 114, Nº2, February 2020

Review Article Cardiac Alterations in Patients with Familial Lipodystrophy Minna Moreira Dias Romano, 1 Paula Ananda Inês Chacon, 1 Fernanda Naira Zambelli Ramalho, 1 Maria Cristina Foss, 1 André Schmid t 2 Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto – Medicina Interna, 1 Ribeirão Preto, SP – Brazil Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto - Centro de Cardiologia, 2 Ribeirão Preto, SP – Brazil Keywords Lipodystrophy, Familial Partial/genetics; Cardiomyopathy, Hypertrophic, Magnetic Resonance Imaging/trends; Metabolic Diseases/complications. Mailing Address: Minna Romano • Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto – Medicina Interna - Campus Universitário USP, S/N. Postal Code 14040-900, Ribeirão Preto, SP – Brasil E-mail: minnaromano@gmail.com Manuscript received January 07, 2019, revised manuscript May 28, 2019, accepted June 05, 2019 DOI: https://doi.org/10.36660/abc.20190016 Abstract Familial lipodystrophy is a rare genetic condition in which individuals have, besides metabolic changes and body fat deposits, a type of cardiomyopathy that has not been well studied. Many of the patients develop cardiovascular changes, the most commonly reported in the literature being the expression of a type of hypertrophic cardiomyopathy. This article, presented as a bibliographic review, reviews the clinical and cardiovascular imaging aspects in this scenario of cardiomyopathy in a rare metabolic disease, based on the latest scientific evidence published in the area. Despite the frequent association of congenital lipodystrophy and ventricular hypertrophy described in the literature, the pathophysiological mechanisms of this cardiomyopathy have not yet been definitively elucidated, and new information on cardiac morphological aspects is emerging in the aegis of recent and advanced imaging methods, such as cardiac magnetic resonance. Introduction Lipodystrophy is a rare disease characterized by the loss of adipose tissue, which may be generalized or partial. 1 Its etiology may be congenital or acquired and there is a deficiency in the leptin hormone production, making the carriers of this pathology hyperphagic. Due to the absence of energy storage sites, an ectopic deposition of triglycerides occurs in the skeletal muscle and liver. 2 The reduced ability to store triglycerides and their ectopic deposition are determinant for the predisposition and severity of complications, such as insulin resistance, diabetes mellitus, hypertriglyceridemia, hepatic steatosis 3 and, recently discovered, cardiomyopathy. Presentations such as left ventricular hypertrophy or even dilated cardiomyopathy have been described in patients with lipodystrophy. Genetic lipodystrophies can be divided and subdivided into various types, each one with its specific mutation, which determine the most diverse clinical presentations and possible associations with the development of heart disease. Despite that, this condition is extremely rare, with a higher prevalence in populations with high levels of consanguinity. This paper aimed to describe familial lipodystrophy and its association with the development of cardiomyopathies, in the light of the latest scientific evidence. Classification of congenital lipodystrophies Congenital Generalized Lipodystrophy (CGL) One of the most frequent types of genetic lipodystrophy is the generalized congenital type, characterized by an autosomal recessive disorder, occurring most often in cases of parental consanguinity. This form is present in all geographical regions and, because of the consanguinity cause, it probably has the highest prevalence reported in some regions of Brazil, such as the Northeast. 4 Individuals with this alteration have an almost total lack of adipose tissue, leading to prominent skeletal musculature regarding its phenotypic aspect. During childhood, many individuals develop hepatosplenomegaly and umbilical prominence; and during adolescence, complications such as diabetes arise. This syndrome can manifest in many different forms, being related to one of four existing subtypes and, consequently, to the affected chromosome. Among these subtypes, the Berardinelli‑Seip syndrome (BSCL) is well-known, described through the scientific collaboration of the great Brazilian researcher W. Berardinelli. Today it is known that this syndrome is identified by a mutation in chromosome 11q13, which encodes the protein seipin, present in the endoplasmic reticulum, being responsible for the formation of lipid droplets and their fusion within adipocytes. Its absence causes a lack of bothmetabolically active adipose tissue andmechanical adipose tissue since birth, whichmay lead tomildmental retardation and cardiomyopathies, making it the most severe of the subtypes. Mandibuloacral dysplasia (MAD) - associated with lipodystrophy This is a type of genetic lipodystrophy, in which the individuals have skeletal abnormalities, such as mandibular and clavicular hypoplasia, associated with skin atrophy, delayed teething, cranial suture closure and joint stiffness. As a common feature of lipodystrophies, MAD leads to metabolic complications such as diabetes, insulin resistance, hypertriglyceridemia, and low HDL-cholesterol levels. Familial partial lipodystrophy (FPL) Familial partial lipodystrophy is, mostly, an autosomal dominant disorder characterized by loss of upper and lower‑limb fat as well as trunk 5 fat. These patients have 305