MON-103 Chromosome 15q13.3 Microdeletion And MAGEL2 Gene Mutation In A Pediatric Patient With Extreme Obesity And Tall Stature: A Case Report

Abstract

Background: Clinical practice guidelines call for consideration of genetic syndromes in evaluation of pediatric patients with extreme early onset obesity with clinical features of genetic obesity syndromes or strong family history of obesity. We describe a case of two genetic variations discovered in an obese pediatric patient. Clinical Case: 10-year-old female of African American descent who presented for evaluation of early onset extreme obesity. Patient noted to have history of hyperphagia with behavioral problems and concern for abnormal coordination. Family history was limited by fact that patient was adopted in infancy without sustained contact with biological family. On physical exam, her height was in the 98th percentile, weight >99th percentile, and BMI 194% of the 95th percentile (Z+3.01). She was noted to have acanthosis nigricans without dysmorphic features. She underwent laboratory evaluation notable for HbA1c in pre-diabetes range at 5.8% (<5.7%) and dyslipidemia with triglycerides elevated at 148mg/dL (35-110mg/dL). Given her early onset of extreme obesity, she underwent genetic testing for obesity syndromes. She was found to have a heterozygous variant of unknown significance of MAGEL2 gene (c. 2572A>T). Although this particular variant has not yet been reported in the literature, a single pathogenic variant in the paternally inherited MAGEL2 gene causes disease. Pathogenic variants in the MAGEL2 gene have been associated with Schaaf-Yang or Prader-Willi-like syndrome. Schaaf-Yang syndrome has clinical overlap with Prader-Willi syndrome with a wide phenotypic spectrum and can include short stature, hypogonadism, intellectual disability, hypotonia, feeding difficulties. Our patient’s clinical phenotype is unique as she has no reported history of hypotonia or feeding difficulties, no intellectual disability, tall stature, and no dysmorphic features on exam. She was noted to have a 1.5MB microdeletion on chromosome 15q13.3 on chromosomal microarray. 15q13.3 microdeletion has been associated with a highly variable phenotype which has been reported to include obesity, intellectual disability, epilepsy, and dysmorphism. Finally, she was found to have a heterozygous variant of unknown significance of TTC8 gene. Homozygous mutations in the TTC8 gene are found in Bardet-Biedl syndrome. Conclusion: This case describes a pediatric patient with extreme obesity found to have both a chromosome 15q13.3 microdeletion and variant in MAGEL2 gene with a unique phenotype. Genetic obesity syndromes should be considered in patients who present with early onset extreme obesity, particularly in the setting of a strong family history, physical exam findings, or neurodevelopmental abnormalities. Reference: Fountain MD, Aten E, Cho MT, et al. The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families. Genet Med. 2016;19(1):45-52.