{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:49:42Z","timestamp":1789454982738,"version":"build-2803163510"},"reference-count":15,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,6,7]],"date-time":"2012-06-07T00:00:00Z","timestamp":1339027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pitt\u2013Hopkins syndrome (PTHS) is an emerging condition characterized by severe intellectual disability (ID), typical facial gestalt, and additional features, such as breathing abnormalities. Because of the overlapping phenotype of severe ID with absent speech, epilepsy, microcephaly, large mouth, and constipation, differential diagnosis of PTHS with respect to Angelman, Rett, and Mowat\u2013Wilson syndromes represents a relevant clinical issue, and many patients are currently undergoing genetic tests for different conditions that are assumed to fall within the PTHS clinical spectrum. During a search for <jats:italic>TCF4<\/jats:italic> mutations in 78 patients with a suspected PTHS, haploinsufficiency of <jats:italic>TCF4<\/jats:italic> was identified in 18. By evaluating clinical features of patients with a proven <jats:italic>TCF4<\/jats:italic> mutation with those of patients without, we noticed that, in addition to the typical facial gestalt, the PTHS phenotype results from the various combination of the following characteristics: ID with severe speech impairment, normal growth parameters at birth, postnatal microcephaly, breathing abnormalities, motor incoordination, ocular anomalies, constipation, seizures, typical behavior, and subtle brain abnormalities. On the basis of these observations, here we propose a clinically based score system as useful tool for driving a first choice molecular test for PTHS. This scoring system is also proposed for a clinically based diagnosis of PTHS in absence of a proven <jats:italic>TCF4<\/jats:italic> mutation. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.35419","type":"journal-article","created":{"date-parts":[[2012,6,7]],"date-time":"2012-06-07T20:12:08Z","timestamp":1339099928000},"page":"1604-1611","source":"Crossref","is-referenced-by-count":27,"title":["Proposal of a clinical score for the molecular test for Pitt\u2013Hopkins syndrome"],"prefix":"10.1002","volume":"158A","author":[{"given":"Giuseppe","family":"Marangi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Ricciardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Orteschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romano","family":"Tenconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo Della","family":"Monica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gioacchino","family":"Scarano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"Battaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Lettori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gessica","family":"Vasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Zollino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,6,7]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/515582"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2007.12.002"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm099"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20935"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20859"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34070"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>3.0.CO;2-E"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1523"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mcd.0000184973.14775.32"},{"key":"e_1_2_5_11_1","first-page":"182","article-title":"A syndrome of mental retardation, wide mouth and intermittent overbreathing","volume":"14","author":"Pitt D","year":"1978","journal-title":"Aust Paediatr J"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181bd38a9"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01380.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21639"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/515583"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.060129"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.35419","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.35419","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T07:55:16Z","timestamp":1697615716000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.35419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,7]]},"references-count":15,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2012,7]]}},"alternative-id":["10.1002\/ajmg.a.35419"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.35419","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6,7]]}}}