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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, Bardet-Biedl, Börjeson-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., (Copyright © 2021. Published by Elsevier Ltd.)