{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T19:52:32Z","timestamp":1786823552565,"version":"build-2736575974"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Here we describe three patients with neurodevelopmental disorders characterized by mild\u2010to\u2010moderate intellectual disability, mildly dysmorphic features, and hirsutism, all of which carry de novo sequence variants in the WW domain\u2010containing adaptor of the coiled\u2010coil (<jats:italic>WAC<\/jats:italic>) gene; two of these\u2014c.167delA, p.(Asn56I1efs*136) and c.1746G&gt;C, p.(Gln582His)\u2014are novel pathogenic variants, and the third\u2014c.1837C&gt;T, p(Arg613*)\u2014has been previously described. Diseases associated with <jats:italic>WAC<\/jats:italic> include DeSanto\u2013Shinawi syndrome; to date, de novo heterozygous constitutional pathogenic WAC variants have caused a syndromic form of intellectual disability and mild dysmorphic features in 33 patients, yet potential associations with other clinical manifestations, such as oligomenorrhea and hyperandrogenism, remain unknown, because the phenotypic spectrum of the condition has not yet been delineated. The patient bearing the novel c.167delA <jats:italic>WAC<\/jats:italic> gene variant presented a normal psychomotor development, oligomenorrhea, hyperandrogenism, and hirsutism, and hirsutism was also observed in the patient with the c.1746G&gt;C <jats:italic>WAC<\/jats:italic> gene variant. Hypertrichosis and hirsutism have been described in nine DeSanto\u2013Shinawi patients, only in 17 of the 33 aforementioned patients thus far reported this aspect, and no hormonal\u2010pattern data are available. In conclusion, we note that the pathogenic c.167delA WAC variant may be associated with a mild phenotype; and in addition to the neurodevelopmental problems nearly all DeSanto\u2013Shinawi patients experience (i.e., intellectual disability and\/or developmental delay), we recommend the addition of mild dysmorphic features, hirsutism, and hypertrichosis to this clinical presentation.<\/jats:p>","DOI":"10.1002\/ajmg.a.63061","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T17:57:17Z","timestamp":1669312637000},"page":"823-830","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Patients with DeSanto\u2013Shinawi syndrome: Further extension of phenotype from Italy"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5674-635X","authenticated-orcid":false,"given":"Daniela","family":"Pasquali","sequence":"first","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalaura","family":"Torella","sequence":"additional","affiliation":[{"name":"Genetica Medica, Department of Precision Medicine University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Pozzuoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Grandone","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health and General and Specialized Surgery University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Luongo","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health and General and Specialized Surgery University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Morleo","sequence":"additional","affiliation":[{"name":"Genetica Medica, Department of Precision Medicine University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Pozzuoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Peduto","sequence":"additional","affiliation":[{"name":"Genetica Medica, Department of Precision Medicine University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"di Fraia","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia Digitale","family":"Selvaggio","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Allosso","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Accardo","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Zanobio","sequence":"additional","affiliation":[{"name":"Genetica Medica, Department of Precision Medicine University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Maitz","sequence":"additional","affiliation":[{"name":"Pediatric Genetics Unit MBBM Foundation, S. 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