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A Comprehensive Review of Syndromic Forms of Obesity: Genetic Etiology, Clinical Features and Molecular Diagnosis

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Abstract

Syndromic obesity refers to obesity occurring with additional clinical findings, such as intellectual disability/developmental delay, dysmorphic features, and congenital malformations.

Purpose of Review

To present a narrative review regarding the genetic etiology, clinical description, and molecular diagnosis of syndromic obesity, which is a rare condition with high phenotypic variability and genetic heterogeneity. The following syndromes are presented in this review: Prader-Willi, Bardet-Biedl, Pseudohypoparathyroidism, Alström, Smith-Magenis, Cohen, Temple, 1p36 deletion, 16p11.2 microdeletion, Kleefstra, SIM1-related, Börjeson-Forssman-Lehmann, WAGRO, Carpenter, MORM, and MYT1L-related syndromes.

Recent Findings

There are three main groups of mechanisms for syndromic obesity: imprinting, transcriptional activity regulation, and cellular cilia function. For molecular diagnostic, methods of genome-wide investigation should be prioritized over sequencing of panels of syndromic obesity genes. In addition, we present novel syndromic conditions that need further delineation, but evidences suggest they have a higher frequency of obesity.

Summary

The etiology of syndromic obesity tends to be linked to disrupted neurodevelopment (central) and is associated with a diversity of genes and biological pathways. In the genetic investigation of individuals with syndromic obesity, the possibility that the etiology of the syndromic condition is independent of obesity should be considered. The accurate genetic diagnosis impacts medical management, treatment, and prognosis, and allows proper genetic counseling.

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Funding

This study was supported by São Paulo Research Foundation - FAPESP (2022/03980–5, 2018/08486–3 and 2013/08028–1), National Council for Scientific and Technological Development - CNPq (3051012022–6 and 303294/2020–5) and Coordination for the Improvement of Higher Education Personnel - CAPES (1805008).

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  1. Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Laboratory of Human Genetics – LGH, Institute of Biosciences, University of São Paulo (USP), Matão Street 277 – Room 350, São Paulo, SP, Brazil

    Laura Machado Lara Carvalho, Débora Romeo Bertola, Ana Cristina Victorino Krepischi & Carla Rosenberg

  2. Genetic Endocrinology Unit, Cellular and Molecular Endocrinology Laboratory (LIM/25), Faculty of Medicine, University of São Paulo (USP), São Paulo, SP, Brazil

    Alexander Augusto de Lima Jorge

  3. Genetics Unit of Instituto da Criança, Faculty of Medicine, University of São Paulo (USP), São Paulo, SP, Brazil

    Débora Romeo Bertola

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  1. Laura Machado Lara Carvalho
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LMLC prepared the first version of the manuscript, figures, and tables. All other authors reviewed and made relevant subsequent contributions.

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Carvalho, L.M.L., Jorge, A.A., Bertola, D.R. et al. A Comprehensive Review of Syndromic Forms of Obesity: Genetic Etiology, Clinical Features and Molecular Diagnosis. Curr Obes Rep (2024). https://doi.org/10.1007/s13679-023-00543-y

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