{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:47:46Z","timestamp":1791978466540,"version":"4.4.0"},"reference-count":11,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T00:00:00Z","timestamp":1586822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Recessive loss-of-function variants in SLC39A13, a putative zinc transporter gene, were first associated with a connective tissue disorder that is now called \u201cEhlers\u2013Danlos syndrome, spondylodysplastic form type 3\u201d (SCD-EDS, OMIM 612350) in 2008. Nine individuals have been described. We describe here four additional affected individuals from three consanguineous families and the follow up of two of the original cases. In our series, cardinal findings included thin and finely wrinkled skin of the hands and feet, characteristic facial features with downslanting palpebral fissures, mild hypertelorism, prominent eyes with a paucity of periorbital fat, blueish sclerae, microdontia, or oligodontia, and\u2014in contrast to most types of Ehlers\u2013Danlos syndrome\u2014significant short stature of childhood onset. Mild radiographic changes were observed, among which platyspondyly is a useful diagnostic feature. Two of our patients developed severe keratoconus, and two suffered from cerebrovascular accidents in their twenties, suggesting that there may be a vascular component to this condition. All patients tested had a significantly reduced ratio of the two collagen-derived crosslink derivates, pyridinoline-to-deoxypyridinoline, in urine, suggesting that this simple test is diagnostically useful. Additionally, analysis of the facial features of affected individuals by DeepGestalt technology confirmed their specificity and may be sufficient to suggest the diagnosis directly. Given that the clinical presentation in childhood consists mainly of short stature and characteristic facial features, the differential diagnosis is not necessarily that of a connective tissue disorder and therefore, we propose that SLC39A13 is included in gene panels designed to address dysmorphism and short stature. This approach may result in more efficient diagnosis.<\/jats:p>","DOI":"10.3390\/genes11040420","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T04:01:46Z","timestamp":1586923306000},"page":"420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Connective Tissue Disorder Associated with Recessive Variants in the SLC39A13 Zinc Transporter Gene (Spondylo-Dysplastic Ehlers\u2013Danlos Syndrome Type 3): Insights from Four Novel Patients and Follow-Up on Two Original Cases"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5764-5470","authenticated-orcid":false,"given":"Camille","family":"Kumps","sequence":"first","affiliation":[{"name":"Division of Genetic Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"Campos-Xavier","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Hilhorst-Hofstee","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Marcelis","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Kraenzlin","sequence":"additional","affiliation":[{"name":"Clinic for Endocrinology, Diabetes &amp; Metabolism, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Fleischer","sequence":"additional","affiliation":[{"name":"FDNA Inc., Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Unger","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3543-7531","authenticated-orcid":false,"given":"Andrea","family":"Superti-Furga","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,14]]},"reference":[{"key":"ref_1","unstructured":"(2002). The Ehlers-Danlos Syndrome. Connective Tissue and Its Heritable Disorders, Wiley-Liss, Inc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1136\/ard.29.3.332","article-title":"Ehlers-Danlos syndrome","volume":"29","author":"Beighton","year":"1970","journal-title":"Ann. Rheum. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ajmg.c.31552","article-title":"The 2017 international classification of the Ehlers-Danlos syndromes","volume":"175","author":"Malfait","year":"2017","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.ajhg.2008.05.001","article-title":"Spondylocheiro dysplastic form of the Ehlers-Danlos syndrome\u2014An autosomal-recessive entity caused by mutations in the zinc transporter gene SLC39A13","volume":"82","author":"Giunta","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Fukada, T., Civic, N., Furuichi, T., Shimoda, S., Mishima, K., Higashiyama, H., Idaira, Y., Asada, Y., Kitamura, H., and Yamasaki, S. (2008). The zinc transporter SLC39A13\/ZIP13 is required for connective tissue development; its involvement in BMP\/TGF-beta signaling pathways. PLoS ONE, 3.","DOI":"10.1371\/annotation\/a6c35a12-e8eb-43a0-9d00-5078fa6da1bb"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1002\/ajmg.a.61366","article-title":"Nosology and classification of genetic skeletal disorders: 2019 revision","volume":"179","author":"Mortier","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1159\/000485881","article-title":"Novel Nonsense Mutation in SLC39A13 Initially Presenting as Myopathy: Case Report and Review of the Literature","volume":"9","author":"Dusanic","year":"2018","journal-title":"Mol. 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Immunol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/4\/420\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:21:10Z","timestamp":1760361670000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/4\/420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,14]]},"references-count":11,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["genes11040420"],"URL":"https:\/\/doi.org\/10.3390\/genes11040420","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,14]]}}}