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These variants are considered to confer a high\u2010risk for the development of severe HCM with poor prognosis and fatal outcome. We report on the natural history of the first adult subject with NS carrying the recurrent pathogenic p.Thr68Ile amino acid substitution. Different from what had previously been observed, he presented with a mild, late\u2010onset left ventricular hypertrophy, and a constellation of additional symptoms rarely seen in NS. The present case provides evidence that HCM does not represent an obligatory, early\u2010onset and severe complication in subjects with <jats:italic>MRAS<\/jats:italic> variants. It also adds new data about late\u2010onset features suggesting that other unexpected complications might be observed in adult subjects providing anticipatory guidance for individuals of all age.<\/jats:p>","DOI":"10.1002\/ajmg.c.32034","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T12:04:09Z","timestamp":1675425849000},"page":"160-166","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Natural history of <i>MRAS<\/i>\u2010related Noonan syndrome: Evidence of mild adult\u2010onset left ventricular hypertrophy and neuropsychiatric features"],"prefix":"10.1002","volume":"193","author":[{"given":"Manuela","family":"Priolo","sequence":"first","affiliation":[{"name":"USD Genetica Medica Grande Ospedale Metropolitano Bianchi\u2010Melacrino\u2010Morelli  Reggio Calabria 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