A novel MYT1L mutation in a boy with syndromic obesity: Case report and literature review

Author(s)

Carvalho, Laura M. L. ^[1] ; D'Angelo, Carla S. ^[1] ; Mustacchi, Zan ^{[2, 3]} ; da Silva, Israel T. ^[4] ; Krepischi, Ana Cristina V. ^[1] ; Koiffmann, Celia P. ^[1] ; Rosenberg, Carla ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Sao Paulo, SP - Brazil

^[2] Darcy Vargas Childrens Hosp HIDV, Genet Outpatient Clin, Sao Paulo, SP - Brazil

^[3] Sao Paulo Ctr Clin Studies & Res CEPEC SP, Sao Paulo, SP - Brazil

^[4] Int Ctr Res, AC Camargo Canc Ctr, Sao Paulo - Brazil

• Document type: Review article
• Source: OBESITY RESEARCH & CLINICAL PRACTICE; v. 15, n. 2, p. 124-132, MAR-APR 2021.
• Web of Science Citations: 0

Abstract

Background: Pathogenic variants involving the MYT1L gene lead to an autosomal dominant form of syndromic obesity, characterized by polyphagia, intellectual disability/developmental delay, and behavioral problems, and that a characteristic facial phenotype does not seem to be recognizable. Methods: Trio whole exome sequencing was performed in a 10-year-old Brazilian male presenting polyphagia, severe early-onset obesity, intellectual disability, speech delay, macrocephaly, frontal bossing, telecanthus, strabismus, and hypogenitalism. Additionally, we performed a literature review of patients carrying non-copy number MYT1L variants. Results: A de novo genetic variant not previously reported in MYT1L (NM 015025.4:c.2990C > A) was identified in the proband and classified as pathogenic. From a literature search, 22 further patients carrying non-copy number MYT1L variants were identified, evidencing that although the associated phenotype is quite variable, intellectual disability/developmental and speech delays are always present. Further, most patients have obesity or overweight due to polyphagia. Macrocephaly, strabismus, behavioral problems, and hand/feet malformations are also recurrent features. Conclusions: We described the first Brazilian case of MYT1L related syndrome and highlighted clinical characteristics based on the literature. Other syndromic forms of obesity such as Prader-Willi, BardetBiedl, B \& ouml;rjeson-Forssman-Lehmann, MORM, Cohen, Alstrom, and Kleefstra type 1 syndromes should be considered in the differential diagnosis. Further, although obesity is frequent, it is not an obligatory feature of all carriers of MYT1L mutations. (c) 2021 Published by Elsevier Ltd on behalf of Asia Oceania Association for the Study of Obesity. (AU)

• 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