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

Author(s)

Carvalho, Laura Machado Lara ; Jorge, Alexander Augusto de Lima ; Bertola, Debora Romeo ; Krepischi, Ana Cristina Victorino ; Rosenberg, Carla

• Document type: Journal article
• Source: CURRENT OBESITY REPORTS; v. 13, n. 2, p. 25-pg., 2024-01-26.

Abstract

Syndromic obesity refers to obesity occurring with additional clinical findings, such as intellectual disability/developmental delay, dysmorphic features, and congenital malformations. Purpose of ReviewTo 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, Alstrom, Smith-Magenis, Cohen, Temple, 1p36 deletion, 16p11.2 microdeletion, Kleefstra, SIM1-related, Borjeson-Forssman-Lehmann, WAGRO, Carpenter, MORM, and MYT1L-related syndromes. Recent FindingsThere 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. SummaryThe 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. (AU)

• FAPESP's process: 22/03980-5 - GENOMIC AND FUNCTIONAL STUDY OF SYNDROMIC FORMS OF INTELLECTUAL DISABILITY
• Grantee: Laura Machado Lara Carvalho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/08486-3 - Genetic bases of Syndromic Obesity and molecular mechanisms involved in its physiopathology
• Grantee: Laura Machado Lara Carvalho
• Support Opportunities: Scholarships in Brazil - Doctorate