{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:33:00Z","timestamp":1790839980339,"version":"4.1.0"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:00:00Z","timestamp":1717027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD) syndrome (OMIM #616266) is an autosomal dominant hereditary disease that can lead to the congenital contracture of the limbs and face, hypotonia, and developmental delay. In addition, it may result in growth retardation and present various clinical symptoms, such as brain atrophy, a small pituitary gland, musculoskeletal abnormalities, abnormal breathing, abdominal hernia, and abnormal facial features. Herein, we describe a novel <jats:italic>de novo<\/jats:italic> missense genetic variant in the sodium leak channel, non-selective (NALCN) gene that is associated with CLIFAHDD syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case description<\/jats:title><jats:p>This study describes a patient with varus deformities in both feet, deviation of the ulnar side of the fingers, and severe hypotonia. This patient was subsequently confirmed to have CLIFAHDD syndrome through genetic testing, which also revealed a novel missense <jats:italic>de novo<\/jats:italic> genetic variant in the NALCN gene (c.3553G\u2009&amp;gt;\u2009A, p.Ala1185Thr).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings further enrich the known variant spectrum of the NALCN gene and may expand the range of clinical options for treating NALCN-related disorders.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2024.1370790","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T04:58:42Z","timestamp":1717045122000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case Report: New presentation of CLIFAHDD syndrome with a novel variant in the NALCN gene and a literature review"],"prefix":"10.3389","volume":"12","author":[{"given":"Yi","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyiyi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.ajhg.2015.01.003","article-title":"De novo mutations in NALCN cause a syndrome characterized by congenital contractures of the limbs and face, hypotonia, and developmental delay","volume":"96","author":"Chong","year":"2015","journal-title":"Am J Hum Genet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1152\/physrev.00014.2022","article-title":"New insights into the physiology and pathophysiology of the atypical sodium leak channel NALCN","volume":"104","author":"Monteil","year":"2024","journal-title":"Physiol Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"11791","DOI":"10.1038\/s41598-019-48071-x","article-title":"Functional expression of CLIFAHDD and IHPRF pathogenic variants of the NALCN channel in neuronal cells reveals both gain- and loss-of-function properties","volume":"9","author":"Bouasse","year":"2019","journal-title":"Sci Rep"},{"key":"B4","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/s41586-020-2570-8","article-title":"Structure of the human sodium leak 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