Study Group: Natural History of Rare Obesity

Study Group:

Natural History of Rare Obesity

Obesity is a highly prevalent and complex disease characterized by excessive body fat accumulation. Obesity often has a multi-factorial cause, including incomplete diet or lack of physical activity. However, in a minority of patients obesity is caused by genetic mutations. Rare genetic obesity disorders encompass a heterogeneous group of conditions, classically divided into non-syndromic and syndromic obesity. These disorders are extremely rare and can be challenging to diagnose. More knowledge on the clinical presentation and core features is needed.

One of the most common types of monogenetic obesity is a defect in the melanocortin 4 receptor (MC4R)-pathway. This pathway, which plays a major role in satiety and energy homeostasis. Defects in the pathway lead to increased food intake, causing characteristic features of monogenetic obesity: (severe) early onset obesity and hyperphagia. So far, more than 150 different mutations in the MC4R gene have been reported. The diagnose can be made by genetic testing. Patients need personalized treatment in specialized centers, since these patients are often refractory to conventional obesity treatment and novel treatments, for example in clinical trials, have become available. However the majority of patients probably still go undiagnosed. The severity of the obesity in patients is variable and a clear clinical phenotype has not been described in larger cohorts yet, only case reports and case series. While severe early-onset obesity and hyperphagia are indeed features of MC4R deficiency, studies have also shown that genetic obesity disorders can cause increased or decreased linear growth and increased or decreased final height. All in all, studies on clinical phenotypic features of MC4R deficiency are scarce and only comprise small numbers of patients.

Objective

Obesity is a highly prevalent and complex disease. A minority of the patients has genetic obesity, which is characterized by hyperphagia and early-onset obesity. However, little is known about other phenotypical characteristics. Therefore, this study will examine growth parameters e.g. BMI, Height and head circumference in patients with genetic obesity. we hope to provide a better description of the phenotype. A better recognition of Genetic Obesity in clinical practice could lead to a faster diagnostic process, better personalized treatment and the prevention of obesity and obesity related comorbidities in the future.

For publications from this and other study groups, see our publication page.

Members of this Study Group

Name(s) Expertise / Role Organisation
Lead: Erica van den Akker pediatric endocrinologist Erasmus MC-Sophia Children’s Hospital, the Netherlands
M. Guftar Shaikh pediatric endocrinologist Royal Hospital for Children, United Kingdom
Hoong-Wei Gan pediatric endocrinologist Great Ormond Street Hospital Institute of Child Health, United Kingdom
Ana Luisa Priego Zurita pediatric endocrinologist, EuRREB fellow Leiden University Medical Center, the Netherlands

For more information regarding the study or if you are interested to contribute to this study, please contact registries@lumc.nl.