Obesity with associated developmental delay and/or learning disability in patients exhibiting additional features: Report of novel pathogenic copy number variants

• Published in: American journal of medical genetics. Part A 2013-03, Vol.161A (3), p.479-486
• Main Authors: D'Angelo, Carla Sustek, Kohl, Ilana, Varela, Monica Castro, de Castro, Cláudia Irene Emílio, Kim, Chong Ae, Bertola, Débora Romeo, Lourenço, Charles Marques, Perez, Ana Beatriz Alvarez, Koiffmann, Celia Priszkulnik
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - genetics; Adolescent; Brain-derived neurotrophic factor; Child; Child, Preschool; developmental disabilities; Developmental Disabilities - diagnosis; Developmental Disabilities - genetics; DNA copy number variants; DNA Copy Number Variations; Female; Humans; Infant; Learning Disorders - diagnosis; Learning Disorders - genetics; Male; Molecular Diagnostic Techniques; obesity; Obesity - diagnosis; Obesity - genetics; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.35761

Obesity is a major threat to public health worldwide, and there is now mounting evidence favoring a role for the central nervous system (CNS) in weight control. A causal relationship has been recognized in both monogenic (e.g., BDNF, TRKB, and SIM1 deficiencies) and syndromic forms of obesity [e.g., Prader–Willi syndrome (PWS)]. Syndromic obesity arising from chromosomal abnormalities, that typically also affect learning and development, are often associated with congenital malformations and behavioral characteristics. We report on nine unrelated patients with a diagnosis of learning disability and/or developmental delay (DD) in addition to obesity that were found to have copy number variants (CNVs) by single nucleotide polymorphism array‐based analysis. Each patient also had a distinct and complex phenotype, and most had hypotonia and other neuroendocrine issues, such as hyperphagia and hypogonadism. Molecular and clinical characterization of these patients enabled us to determine with confidence that the CNVs we observed were pathogenic or likely to be pathogenic. Overall, the CNVs reported here encompassed a candidate gene or region (e.g., SIM1) that has been reported in patients associating obesity and DD and/or intellectual disability (ID) and novel candidate genes and regions. © 2013 Wiley Periodicals, Inc.