{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:05:49Z","timestamp":1791644749656,"version":"4.3.4"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,24]],"date-time":"2023-12-24T00:00:00Z","timestamp":1703376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pomost","award":["N110\/0003\/21"],"award-info":[{"award-number":["N110\/0003\/21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Nager syndrome is a rare human developmental disorder characterized by craniofacial defects including the downward slanting of the palpebral fissures, cleft palate, limb deformities, mandibular hypoplasia, hypoplasia or absence of thumbs, microretrognathia, and ankylosis of the temporomandibular joint. The prevalence is very rare and the literature describes only about a hundred cases of Nager syndrome. There is evidence of autosomal dominant and autosomal recessive inheritance for Nager syndrome, suggesting genetic heterogeneity. The majority of the described causes of Nager syndrome include pathogenic variants in the SF3B4 gene, which encodes a component of the spliceosome; therefore, the syndrome belongs to the spliceosomopathy group of diseases. The diagnosis is made on the basis of physical and radiological examination and detection of mutations in the SF3B4 gene. Due to the diversity of defects associated with Nager syndrome, patients require multidisciplinary, complex, and long-lasting treatment. Usually, it starts from birth until the age of twenty years. The surgical procedures vary over a patient\u2019s lifetime and are related to the needed function. First, breathing and feeding must be facilitated; then, oral and facial clefts should be addressed, followed by correcting eyelid deformities and cheekbone reconstruction. In later age, a surgery of the nose and external ear is performed. Speech and hearing disorders require specialized logopedic treatment. A defect of the thumb is treated by transplanting a tendon and muscle or transferring the position of the index finger. In addition to surgery, in order to maximize a patient\u2019s benefit and to reduce functional insufficiency, complementary treatments such as rehabilitation and physiotherapy are recommended. In our study, we describe eight patients of different ages with various cases of Nager syndrome. The aim of our work was to present the actual genetic knowledge on this disease and its treatment procedures.<\/jats:p>","DOI":"10.3390\/genes15010029","type":"journal-article","created":{"date-parts":[[2023,12,24]],"date-time":"2023-12-24T20:44:15Z","timestamp":1703450655000},"page":"29","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Children with Rare Nager Syndrome\u2014Literature Review, Clinical and Physiotherapeutic Management"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2635-1074","authenticated-orcid":false,"given":"Bo\u017cena Anna","family":"Marsza\u0142ek-Kruk","sequence":"first","affiliation":[{"name":"Department of Genetics, Wroclaw University of Environmental and Life Sciences, 51-631 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2183-1156","authenticated-orcid":false,"given":"Andrzej","family":"My\u015bliwiec","sequence":"additional","affiliation":[{"name":"Laboratory of Physiotherapy and Physioprevention, Institute of Physiotherapy and Health Sciences, Academy of Physical Education in Katowice, 40-065 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9182-6953","authenticated-orcid":false,"given":"Anna","family":"Lipowicz","sequence":"additional","affiliation":[{"name":"Department of Anthropology, Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4553-3479","authenticated-orcid":false,"given":"Wojciech","family":"Wola\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Biomechatronics, Faculty of Biomedical Engineering, Silesian University of Technology, 41-800 Zabrze, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Kulesa-Mrowiecka","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation in Internal Diseases, Faculty of Health Sciences, Jagiellonian University Medical College, 31-126 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7605-2080","authenticated-orcid":false,"given":"Krzysztof","family":"Dowgierd","sequence":"additional","affiliation":[{"name":"Head and Neck Surgery Clinic for Children and Young Adults, Department of Clinical Pediatrics, Collegium Medicum, University of Warmia and Mazury, 10-561 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/cge.12123","article-title":"Human facial dysostoses","volume":"83","author":"Wieczorek","year":"2013","journal-title":"Clin. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.bjps.2016.12.014","article-title":"Ankylosis of temporomandibular joints after mandibular distraction osteogenesis in patients with Nager syndrome: Report of two cases and literature review","volume":"70","author":"Wu","year":"2017","journal-title":"J. Plast. Reconstr. Aesthetic Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.joms.2011.02.053","article-title":"Temporomandibular joint replacement for ankylosis correction in Nager syndrome: Case report and review of the literature","volume":"70","author":"Schlieve","year":"2012","journal-title":"J. Oral. Maxillofac. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Witkowski, R., Prokop, O., and Ullrich, E. (1995). Lexikon der Syndrome und Fehlbildungen, Springer.","DOI":"10.1007\/978-3-642-97628-5"},{"key":"ref_5","first-page":"984732","article-title":"Dental Management of a Patient with Nager Acrofacial Dysostosis","volume":"2015","year":"2015","journal-title":"Case Rep. Dent."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1136\/jmg.30.9.779","article-title":"Nager acrofacial dysostosis","volume":"30","author":"McDonald","year":"1993","journal-title":"J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1177\/10556656221089156","article-title":"SF3B4 Frameshift Variants Represented a More Severe Clinical Manifestation in Nager Syndrome","volume":"60","author":"Ulhaq","year":"2023","journal-title":"Cleft Palate Craniofac. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejmg.2015.12.001","article-title":"Prenatal diagnosis of Nager syndrome in a 12-week-old fetus with a whole gene deletion of SF3B4 by chromosomal microarray","volume":"59","author":"Lund","year":"2016","journal-title":"Eur. J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1002\/dvdy.214","article-title":"Spliceosomopathies: Diseases and mechanisms","volume":"249","author":"Griffin","year":"2020","journal-title":"Dev. Dyn."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.ajhg.2012.04.004","article-title":"Haploinsufficiency of SF3B4, a component of the pre-mRNA spliceosomal complex, causes Nager syndrome","volume":"90","author":"Bernier","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1101\/gad.8.16.1974","article-title":"The prespliceosome components SAP 49and SAP 145 interact in a complex implicated in tethering U2 snRNPto the branch site","volume":"8","author":"Reed","year":"1994","journal-title":"Genes Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20728","DOI":"10.1074\/jbc.M703292200","article-title":"Splicing factor 3b subunit 4 binds BMPR-IA and inhibits osteochondral cell differentiation","volume":"282","author":"Watanabe","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/ccr3.2509","article-title":"Second-trimester prenatal diagnosis of Nager syndrome with a deletion including SF3B4detected by chromosomal microarray","volume":"8","author":"Drozniewska","year":"2020","journal-title":"Clin. Case Rep."},{"key":"ref_14","first-page":"30","article-title":"Nager acrofacial dysostosis in four patients including monozygous twins","volume":"7","author":"Byrd","year":"1988","journal-title":"Proc. Greenwood Genet. Center"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/1096-8628(20000619)92:5<373::AID-AJMG19>3.0.CO;2-Q","article-title":"Heterogeneity and minor anomalies","volume":"92","author":"Opitz","year":"2000","journal-title":"Am. J. Med. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/pd.2214","article-title":"Prenatal diagnosis of Nager syndrome in a monochorionic-diamniotic twin pregnancy","volume":"29","author":"Ghoumid","year":"2009","journal-title":"Prenat. Diagn."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.pedneo.2012.01.014","article-title":"Nager Syndrome: A Case Report","volume":"53","author":"Lin","year":"2012","journal-title":"Pediatr. Neonatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s00439-013-1295-2","article-title":"Clinical and mutation data in 12 patients with the clinical diagnosis of Nager syndrome","volume":"132","author":"Czeschik","year":"2013","journal-title":"Hum Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/cge.12259","article-title":"Nager syndrome: Confirmation of SF3B4 haploinsufficiency as the major cause","volume":"86","author":"Petit","year":"2014","journal-title":"Clin. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1002\/ajmg.a.36555","article-title":"Rodriguez syndrome with SF3B4 mutation: A severe form of Nager syndrome?","volume":"164","author":"McPherson","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e23426","DOI":"10.1002\/jcla.23426","article-title":"Broad-spectrum next-generation sequencing-based diagnosis of a case of Nager syndrome","volume":"34","author":"Zhao","year":"2020","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.cancergen.2021.01.025","article-title":"Prenatal diagnosis of Acrofacial Dysostosis type 1 (Nager syndrome) by chromosomal microarray at the exon level","volume":"252\u2013253","author":"Drendel","year":"2021","journal-title":"Cancer Genet."},{"key":"ref_23","first-page":"2050313X221144219","article-title":"First case report of Nager syndrome patient from Georgia","volume":"10","author":"Tkemaladze","year":"2022","journal-title":"Med. Case Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rutka, M., My\u015bliwiec, A., Wolny, T., Gogola, A., and Linek, P. (2021). Influence of Chest and Diaphragm Manual Therapy on the Spirometry Parameters in Patients with Cerebral Palsy: A Pilot Study. Biomed Res. Int., 2021.","DOI":"10.1155\/2021\/6263973"},{"key":"ref_25","first-page":"3187","article-title":"Efficacy of immediate physiotherapy after surgical release of zygomatico-coronoid ankylosis in a young child: A Case Report","volume":"38","author":"Dowgierd","year":"2021","journal-title":"Int. J. Phys. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kulesa-Mrowiecka, M., Piech, J., Dowgierd, K., and My\u015bliwiec, A. (2021). Physical therapy of temporomandibular disorder in a child with arthrogryposis multiplex congenita: A case report and literature review. J. Craniomandib. Sleep Pract., 1\u20138.","DOI":"10.1080\/08869634.2021.1890453"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"93","DOI":"10.20966\/chn.2017.52.399","article-title":"Case of a child with Nager\u2019s syndrome\u2014Diagnosis and rehabilitation","volume":"26","author":"Dytrych","year":"2017","journal-title":"Child Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1002\/ajmg.a.61121","article-title":"The final demise of Rodriguez lethal acrofacial dysostosis: A case report and review of the literature","volume":"179","author":"Drivas","year":"2019","journal-title":"Am. J. Med. Genet. A"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/1\/29\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:41:14Z","timestamp":1760132474000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/1\/29"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,24]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["genes15010029"],"URL":"https:\/\/doi.org\/10.3390\/genes15010029","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,24]]}}}