Dunnigan-Type Familial Partial Lipodystrophy: Understanding and Treating the Syndrome

Dunnigan-type partial lipodystrophy, which is characterized by a number of metabolic alterations, change in body fat distribution, and autosomal dominant inheritance pattern, is rare in the general population. Objective: To report the case of an adolescent with clinical and laboratory findings suggestive of Dunnigan-type partial lipodystrophy. Methods: Case report and literature review. Results: A 15-year-old adolescent presented at the clinic complaining of darkening of skin folds on her trunk and back. During physical examination, the presence of serious acanthosis nigricans in her cervical region, axillae, and intergluteal space was noted. Hirsutism in androgen-dependent areas was also observed, as well as relevant reduction of subcutaneous adipose tissue in the limbs, gluteal region, abdomen, and trunk and fat accumulation in the face and chin. Discussion. Dunnigan-type familial partial lipodystrophy is a rare dominant autosomal disease resulting from a heterozygous missense mutation in the LMNA gene, known as LPF type 2 (Dunnigan variant), which encodes the nuclear protein A/C-type lamin. It is characterized by the progressive disappearance of the subcutaneous adipose tissue in the limbs, gluteal region, abdomen, and trunk, with onset in puberty, followed by fat accumulation in other areas such as the face, chin, labia majora, and intra-abdominal region, leading to hypertrophy that may mimic the Cushing’s syndrome phenotype. Affected patients display marked insulin resistance and may consequently develop diabetes mellitus, acanthosis nigricans, hirsutism, and polycystic ovary syndrome. Conclusion: This case report highlights the importance of suspecting Dunnigan-type familial partial lipodystrophy in clinical practice. Early clinical diagnosis allows for measures that minimize the severe metabolic disorders associated with this disease and, consequently, these adolescents’ self-esteem issues.

Endocrine Disruptors and Fetal Programming

The concept “fetal programming” shows who still in the intrauterine life, can interfere in factors related to the genesis and development of diseases in childhood, adolescence and adult life. The literature shows that children born to mothers with gestational diabetes mellitus (GDM) are at increased risk for the development of obesity in adulthood, it becomes fundamental to study more about the subject. Obesity is a disease of multifactorial etiology, resulting from complex interactions between genetic and environmental factors. However, the marked increase in its incidence, precocity and severity are not yet fully understood. Several findings suggest that stressor stimuli (e.g. diabetes, nutritional changes) during intrauterine development may promote epigenetic changes, as well as affect mitochondrial metabolism, which may modulate fetal development and predispose to the late development of diseases. Despite the considerable amount of evidence accumulated about intrauterine programming for diseases of adult life, the determinant mechanisms of such programming are not yet clear.