{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:38:21Z","timestamp":1789699101419,"version":"4.0.1"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of National Economy, Hungary","award":["GINOP-2.3.2-15-2016-00039"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00039"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The ADNP-gene-related neurodevelopmental disorder Helsmoortel\u2013Van der Aa syndrome is a rare syndromic-intellectual disability\u2014an autism spectrum disorder first described by Helsmoortel and Van der Aa in 2014. Recently, a large cohort including 78 patients and their detailed phenotypes were presented by Van Dijck et al., 2019, who reported developmental delay, speech delay and autism spectrum disorder as nearly constant findings with or without variable cardiological, gastroenterological, urogenital, endocrine and neurological manifestations. Among cardiac malformations, atrial septal defect, patent ductus arteriosus, patent foramen ovale and mitral valve prolapse were the most common findings, but other unspecified defects, such as mild pulmonary valve stenosis, were also described. We present two patients with pathogenic ADNP variants and unusual cardiothoracic manifestations\u2014Bland\u2013White\u2013Garland syndrome, pectus carinatum superiorly along the costochondral junctions and pectus excavatum inferiorly in one patient, and Kawasaki syndrome with pericardiac effusion, coronary artery dilatation and aneurysm in the other\u2014who were successfully treated with intravenous immunoglobulin, corticosteroid and aspirin. Both patients had ectodermal and\/or skeletal features overlapping those seen in RASopathies, supporting the observations of Alkhunaizi et al. 2018. on the clinical overlap between Helsmoortel\u2013Van der Aa syndrome and Noonan syndrome. We observed a morphological overlap with the Noonan-like disorder with anagen hair in our patients.<\/jats:p>","DOI":"10.3390\/genes13122367","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T03:43:49Z","timestamp":1671075829000},"page":"2367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Helsmoortel\u2013Van der Aa Syndrome\u2014Cardiothoracic and Ectodermal Manifestations in Two Patients as Further Support of a Previous Observation on Phenotypic Overlap with RASopathies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6634-4381","authenticated-orcid":false,"given":"T\u00edmea Margit","family":"Szab\u00f3","sequence":"first","affiliation":[{"name":"Institute of Paediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3397-2829","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Balogh","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9178-5282","authenticated-orcid":false,"given":"Anik\u00f3","family":"Ujfalusi","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2836-3383","authenticated-orcid":false,"given":"Zsuzsanna","family":"Sz\u0171cs","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Madar","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Koczok","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Be\u00e1ta","family":"Bessenyei","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildik\u00f3","family":"Cs\u00fcrke","sequence":"additional","affiliation":[{"name":"J\u00f3sa Andr\u00e1s Hospital, Szabolcs-Szatm\u00e1r-Bereg County Hospitals and University Teaching Hospital, 4400 Ny\u00edregyh\u00e1za, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2659-7488","authenticated-orcid":false,"given":"Katalin","family":"Szakszon","sequence":"additional","affiliation":[{"name":"Institute of Paediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.biopsych.2018.02.1173","article-title":"Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP","volume":"85","author":"Silfhout","year":"2019","journal-title":"Biol. 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