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It had been suspected that mutations in <jats:italic>Methyl\u2010CpG\u2010binding protein 2<\/jats:italic> (<jats:italic>MECP2<\/jats:italic>) led to embryonic lethality in males, however such males have been reported. To enhance understanding of the phenotypic spectrum present in these individuals, we identified 30 males with <jats:italic>MECP2<\/jats:italic> mutations in the RTT Natural History Study databases. A wide phenotypic spectrum was observed, ranging from severe neonatal encephalopathy to cognitive impairment. Two males with a somatic mutation in <jats:italic>MECP2<\/jats:italic> had classic RTT. Of the remaining 28 subjects, 16 had RTT\u2010causing <jats:italic>MECP2<\/jats:italic> mutations, 9 with mutations that are not seen in females with RTT but are likely pathogenic, and 3 with uncertain variants. Two subjects with RTT\u2010causing mutations were previously diagnosed as having atypical RTT; however, careful review of the clinical history determined that an additional 12\/28 subjects met criteria for atypical RTT, but with more severe clinical presentation and course, and less distinctive RTT features, than females with RTT, leading to the designation of a new diagnostic entity, male RTT encephalopathy. Increased awareness of the clinical spectrum and widespread comprehensive genomic testing in boys with neurodevelopmental problems will lead to improved identification.<\/jats:p>","DOI":"10.1002\/ajmg.b.32707","type":"journal-article","created":{"date-parts":[[2018,12,7]],"date-time":"2018-12-07T17:22:31Z","timestamp":1544203351000},"page":"55-67","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["The array of clinical phenotypes of males with mutations in <i>Methyl\u2010CpG binding protein 2<\/i>"],"prefix":"10.1002","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5628-5872","authenticated-orcid":false,"given":"Jeffrey L.","family":"Neul","sequence":"first","affiliation":[{"name":"Vanderbilt University Medical Center  Nashville Tennessee"},{"name":"University of California  San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy 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