{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:23:52Z","timestamp":1792103032767,"version":"4.4.0"},"reference-count":14,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,22]],"date-time":"2022-05-22T00:00:00Z","timestamp":1653177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Menke\u2013Hennekam syndrome (MHS) is a rare and recently described syndrome consecutive to the variants in exon 30 or 31 in CREBBP (CREB-binding protein gene). The CREB-binding protein (CREBBP) and EP300 genes are two commonly expressed genes whose products possess acetyltransferase activity for histones and various other proteins. Mutations that affect these two genes are known to cause Rubinstein\u2013Taybi syndrome (RTS); however, with the application of whole exome sequencing (WES) there were reports of variants that affect specific regions of exon 30 or 31 of these two genes but without the specific phenotype of RTS. Material and Methods: A review of the available literature was conducted, aimed at underscoring the difficulties in diagnosing MHS based on phenotype particularities. Results: Five applicable studies were identified by searching PubMed, Web of Science, and Scopus databases for publications up to November 2021 using the key terms \u201cMenke\u2013Hennekam syndrome\u201d and \u201cCREBBP\u201d. Conclusions: In this paper, we present a new case and highlight the importance of exome sequencing to identify different mutations of exons 30 and 31 of the CREBBP gene involved in MHS, and we make formal recommendations based on our literature review.<\/jats:p>","DOI":"10.3390\/children9050759","type":"journal-article","created":{"date-parts":[[2022,5,22]],"date-time":"2022-05-22T07:13:57Z","timestamp":1653203637000},"page":"759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Menke\u2013Hennekam Syndrome: A Literature Review and a New Case Report"],"prefix":"10.3390","volume":"9","author":[{"given":"Aurora","family":"Sima","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, \u201cGrigore Alexandrescu\u201d Emergency Hospital for Children, 011743 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana Elena","family":"Sm\u0103deanu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, \u201cGrigore Alexandrescu\u201d Emergency Hospital for Children, 011743 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9334-0199","authenticated-orcid":false,"given":"Anca Angela","family":"Simionescu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Carol Davila University of Medicine and Pharmacy, Filantropia Clinical Hospital, 011132 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florina","family":"Nedelea","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Carol Davila University of Medicine and Pharmacy, Filantropia Clinical Hospital, 011132 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea-Maria","family":"Vlad","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, \u201cGrigore Alexandrescu\u201d Emergency Hospital for Children, 011743 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Becheanu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, \u201cGrigore Alexandrescu\u201d Emergency Hospital for Children, 011743 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/carcin\/bgz149","article-title":"Mutations in CREBBP and EP300 genes affect DNA repair of oxidative damage in Rubinstein-Taybi syndrome cells","volume":"3","author":"Dutto","year":"2020","journal-title":"Carcinogenesis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13052-015-0110-1","article-title":"Rubinstein-Taybi syndrome: Clinical features, genetic basis, diagnosis, and management","volume":"41","author":"Milani","year":"2015","journal-title":"Ital. J. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1002\/ajmg.a.37800","article-title":"CREBBP mutations in individuals without Rubinstein-Taybi syndrome phenotype","volume":"170","author":"Menke","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1002\/ajmg.a.61131","article-title":"Genotype-phenotype specificity in Menke-Hennekam syndrome caused by missense variants in exon 30 or 31 of CREBBP","volume":"179","author":"Banka","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1002\/ajmg.a.62533","article-title":"The novel and recurrent variants in exon 31 of CREBBP in Japanese patients with Menke-Hennekam syndrome","volume":"188","author":"Nishi","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"a026534","DOI":"10.1101\/cshperspect.a026534","article-title":"Exploitation of EP300 and CREBBP Lysine Acetyltransferases by Cancer","volume":"7","author":"Attar","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1086\/429130","article-title":"Genetic heterogeneity in Rubinstein-Taybi syndrome: Mutations in both the CBP and EP300 genes cause disease","volume":"76","author":"Roelfsema","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s12017-013-8285-3","article-title":"Epigenetic mechanisms of Rubinstein-Taybi syndrome","volume":"16","author":"Park","year":"2014","journal-title":"Neuromol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1101\/gad.14.13.1553","article-title":"CBP\/p300 in cell growth, transformation, and development","volume":"14","author":"Goodman","year":"2000","journal-title":"Genes Dev."},{"key":"ref_10","first-page":"633","article-title":"EP300 (E1A binding protein p300)","volume":"19","author":"Negri","year":"2017","journal-title":"Atlas Genet. Cytogenet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1002\/ajmg.a.38626","article-title":"Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein-Taybi syndrome","volume":"176","author":"Menke","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/ajmg.a.61052","article-title":"Confirmation of a new phenotype in an individual with a variant in the last part of exon 30 of CREBBP","volume":"179","author":"Angius","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_13","first-page":"461","article-title":"The clinical features of individuals of Menke-Hennekam syndrome. Meeting abstract","volume":"28","author":"Nishi","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_14","first-page":"471","article-title":"Menke-Hennekam syndrome subtypes caused by variants in the Zinc finger domains ZZ and TAZ2 and the fourth intrinsically disordered linker of CBP and Meeting abstract","volume":"28","author":"Menke","year":"2020","journal-title":"Eur. J. Hum. Genet."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/5\/759\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:16:33Z","timestamp":1760138193000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/5\/759"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,22]]},"references-count":14,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["children9050759"],"URL":"https:\/\/doi.org\/10.3390\/children9050759","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,22]]}}}