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Silvia Sequeira1, Oana Moldovan2, Ana Catarina Alves3, Ana Medeiros3, Mafalda Bourbon3

1- Unidade de Doenças Metabólicas, Área Pediatria Médica, Hospital Dona Estefânia, CHLC
2- Unidade de Genética, Departamento de Pediatria, Hospital Santa Maria
3- Grupo de Investigação Cardiovascular, Unidade de Investigação e Desenvolvimento,  Departamento de Promoção da Saúde e Doenças Crónicas,  Instituto Nacional de Saúde Dr. Ricardo Jorge

- Poster no XI Simpósio Internacional da Sociedade Portuguesa de Doenças Metabólicas,  Porto, 19 a 20 de Março de 2015
- Poster no SSIEM Annual Symposium, Lyon, 1 a 4 Setembro de 2015

Introduction: Dunnigan syndrome, a dominant disorder, is the most prevalent form of familial partial lipodystrophy (FPLD2) with an estimated prevalence of 1:15 million persons. Lipodystrophy (LD) is a clinical diagnosis based on findings from the physical examination showing fat loss or abnormal adipose tissue redistribution. The children affected with FPLD2 are born with normal fat distribution and may present hyperlipidemia in childhood. Later on they have selective loss of fat in the lower limbs and trunk and accumulation of fat in the face, neck and supraclavicular fossa. The affected adults may have metabolic syndrome including high blood pressure, insulin resistance, diabetes mellitus, liver steatosis hypertriglyceridemia, and low HDL- cholesterol levels and therefore and increased risk of cardiovascular events.
Case Report: We report a family in which death of a 52 year-old male due to an episode of myocardial infarction led to the investigation of the extended family. The lipid levels, similar to familial combined hyperlipidemia, and abnormal phenotype suggested the diagnosis of Dunningan syndrome. The sequencing of lamin A/C (LMNA) gene was performed by PCR and direct sequencing of all exons. The index patient revealed a heterozygous missense mutation, p.R482W. All family members were subsequently screened for this mutation, confirming the heterozygous status in four additional relatives, including two children. One of these children, a 17-year- -old girl, despite having normal glucose and lipid levels already presents signs of a partial LD. We present the clinical, biochemical and molecular characterization of this large Portuguese family with several affected family members of different ages.
Comments: The high prevalence of premature and severe cardiovascular complications in these patients make the early diagnosis of this condition essential for the treatment strategy and anticipation of disease progression. There are no established guidelines for the treatment of LD and current treatment is mainly a leading a healthy life style with a proper diet, exercise and eventual treatment of hypertension, dyslipidemia and diabetes. As there are reduced circulating levels of hormones secreted by adipose tissue, as leptin and adiponectin, these, peroxisome proliferator-activated receptor gamma, growth hormone (GH) and GH-releasing factors are being tested and could potentially revolutionize the treatment of this difficult-to-treat condition.