{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T01:24:34Z","timestamp":1778203474067,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"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>Wiedemann\u2013Steiner syndrome (WDSTS) is an autosomal dominant disorder with a broad and variable phenotypic spectrum characterized by intellectual disability, prenatal and postnatal growth retardation, hypertrichosis, characteristic facial features, behavioral problems, and congenital anomalies involving different systems. Here, we report a five-year-old boy who was diagnosed with WDSTS based on the results of Trio-based whole-exome sequencing and an assessment of his clinical features. He had intellectual disability, short stature, hirsutism, and atypical facial features, including a low hairline, down-slanting palpebral fissures, hypertelorism, long eyelashes, broad and arching eyebrows, synophrys, a bulbous nose, a broad nasal tip, and dental\/oral anomalies. However, not all individuals with WDSTS exhibit the classic phenotype, so the spectrum of the disorder can vary widely from relatively atypical facial features to multiple systemic symptoms. Here, we summarize the clinical and molecular spectrum, diagnosis and differential diagnosis, long-term management, and care planning of WDSTS to improve the awareness of both pediatricians and clinical geneticists and to promote the diagnosis and treatment of the disease.<\/jats:p>","DOI":"10.3390\/children9101545","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T05:31:18Z","timestamp":1665552678000},"page":"1545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Wiedemann\u2013Steiner Syndrome: Case Report and Review of Literature"],"prefix":"10.3390","volume":"9","author":[{"given":"Huan","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guijiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengxu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"ref_1","unstructured":"Wiedemann, H.R., Kunze, J., Grosse, F.R., and Dibbern, H. (1989). A syndrome of abnormal facies, short stature, and psychomotor retar-dation. Atlas Clin. Syndr. A Vis. Aid Diagn. Clin. Pract. Physicians, 198\u2013199."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1097\/00019605-200009020-00021","article-title":"Growth deficiency, mental retardation and unusual facies","volume":"9","author":"Steiner","year":"2000","journal-title":"Clin. Dysmorphol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.ajhg.2012.06.008","article-title":"De novo mutations in MLL cause Wiedemann-Steiner syndrome","volume":"91","author":"Jones","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1074\/mcp.M113.035600","article-title":"Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics","volume":"13","author":"Fagerberg","year":"2014","journal-title":"Mol. Cell. Proteom. MCP"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E64","DOI":"10.1097\/PEP.0000000000000714","article-title":"Physical Therapy Management of Wiedemann-Steiner Syndrome From Birth to 3 Years","volume":"32","author":"Mendoza","year":"2020","journal-title":"Pediatr. Phys. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1210\/jcem-21-11-1440","article-title":"Clinical assessment of body hair growth in women","volume":"21","author":"Ferriman","year":"1961","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1002\/ajmg.a.62124","article-title":"Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome","volume":"185","author":"Sheppard","year":"2021","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/cge.13254","article-title":"Wiedemann-Steiner syndrome as a major cause of syndromic intellectual disability: A study of 33 French cases","volume":"94","author":"Baer","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1186\/s13023-018-0909-0","article-title":"Description of the molecular and phenotypic spectrum of Wiedemann-Steiner syndrome in Chinese patients","volume":"13","author":"Li","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1002\/ajmg.a.33587","article-title":"Wiedemann-Steiner syndrome: Three further cases","volume":"152","author":"Koenig","year":"2010","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41431-017-0033-y","article-title":"Molecular and cellular issues of KMT2A variants involved in Wiedemann-Steiner syndrome","volume":"26","author":"Lebrun","year":"2018","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41431-020-0679-8","article-title":"Expanding the phenotype associated to KMT2A variants: Overlapping clinical signs between Wiedemann-Steiner and Rubinstein-Taybi syndromes","volume":"29","author":"Massa","year":"2021","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1002\/ajmg.a.37681","article-title":"Congenital immunodeficiency in an individual with Wiedemann-Steiner syndrome due to a novel missense mutation in KMT2A","volume":"170","author":"Stellacci","year":"2016","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e19813","DOI":"10.1097\/MD.0000000000019813","article-title":"Wiedemann-steiner syndrome with a de novo mutation in KMT2A: A case report","volume":"99","author":"Jinxiu","year":"2020","journal-title":"Medicine"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Strom, S.P., Lozano, R., Lee, H., Dorrani, N., Mann, J., O\u2019Lague, P.F., Mans, N., Deignan, J.L., Vilain, E., and Nelson, S.F. (2014). De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing. BMC Med. Genet., 15.","DOI":"10.1186\/1471-2350-15-49"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/ajmg.a.60698","article-title":"The progression of Wiedemann-Steiner syndrome in adulthood and two novel variants in the KMT2A gene","volume":"179","author":"Feldman","year":"2019","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ng, R., Harris, J., Fahrner, J.A., and Bjornsson, H.T. (2022). Individuals with Wiedemann-Steiner syndrome show nonverbal reasoning and visuospatial defects with relative verbal skill sparing. J. Int. Neuropsychol. Soc. JINS, 1\u20137.","DOI":"10.1017\/S1355617722000467"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.2106\/JBJS.CC.21.00623","article-title":"Severe Hip Dysplasia in Wiedemann-Steiner Syndrome Treated with Bilateral Bernese Periacetabular Osteotomy: A Case Report","volume":"12","author":"Evans","year":"2022","journal-title":"JBJS Case Connect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1002\/ajmg.a.36590","article-title":"Advanced bone age in a girl with Wiedemann-Steiner syndrome and an exonic deletion in KMT2A (MLL)","volume":"164","author":"Mendelsohn","year":"2014","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_20","first-page":"e15203","article-title":"Feeding disorder in a patient with Wiedemann-Steiner syndrome","volume":"64","author":"Iijima","year":"2022","journal-title":"Pediatr. Int. Off. J. Jpn. Pediatr. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3702","DOI":"10.1038\/s41598-017-02434-4","article-title":"Early-onset primary antibody deficiency resembling common variable immunodeficiency challenges the diagnosis of Wiedeman-Steiner and Roifman syndromes","volume":"7","author":"Bogaert","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhang, H., Xiang, B., Chen, H., Chen, X., and Cai, T. (2019). A novel deletion mutation in KMT2A identified in a child with ID\/DD and blood eosinophilia. BMC Med. Genet., 20.","DOI":"10.1186\/s12881-019-0776-0"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e1533","DOI":"10.1002\/mgg3.1533","article-title":"Trio-WES reveals a novel de novo missense mutation of KMT2A in a Chinese patient with Wiedemann-Steiner syndrome: A case report","volume":"9","author":"Wang","year":"2021","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s12017-018-8502-1","article-title":"RNA Sequencing and Pathway Analysis Identify Important Pathways Involved in Hypertrichosis and Intellectual Disability in Patients with Wiedemann-Steiner Syndrome","volume":"20","author":"Mietton","year":"2018","journal-title":"Neuromolecular Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41525-019-0083-x","article-title":"Expanding the neurodevelopmental phenotypes of individuals with de novo KMT2A variants","volume":"4","author":"Chan","year":"2019","journal-title":"npj Genom. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/sj.ejhg.5200987","article-title":"Mutations in PAX1 may be associated with Klippel-Feil syndrome","volume":"11","author":"McGaughran","year":"2003","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tracy, M.R., Dormans, J.P., and Kusumi, K. (2004). Klippel-Feil syndrome: Clinical features and current understanding of etiology. Clin. Orthop. Relat. Res., 183\u2013190.","DOI":"10.1097\/01.blo.0000130267.49895.20"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Reynisdottir, T., Anderson, K.J., Boukas, L., and Bjornsson, H.T. (2022). Missense variants causing Wiedemann-Steiner syndrome preferentially occur in the KMT2A-CXXC domain and are accurately classified using AlphaFold2. PLoS Genet., 18.","DOI":"10.1101\/2022.01.03.474770"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"40","DOI":"10.25100\/cm.v50i1.3555","article-title":"Wiedemann-Steiner syndrome with a novel pathogenic variant in KMT2A: A case report","volume":"50","author":"Pachajoa","year":"2019","journal-title":"Colomb. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"252ra123","DOI":"10.1126\/scitranslmed.3009262","article-title":"Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome","volume":"6","author":"Zemojtel","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/s10038-019-0619-z","article-title":"Evaluation of Face2Gene using facial images of patients with congenital dysmorphic syndromes recruited in Japan","volume":"64","author":"Mishima","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1159\/000511971","article-title":"Wiedemann-Steiner Syndrome as a Differential Diagnosis of Cornelia de Lange Syndrome Using Targeted Next-Generation Sequencing: A Case Report","volume":"12","author":"Demir","year":"2021","journal-title":"Mol. Syndr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00439-019-01985-y","article-title":"Exploring by whole exome sequencing patients with initial diagnosis of Rubinstein-Taybi syndrome: The interconnections of epigenetic machinery disorders","volume":"138","author":"Negri","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s00439-015-1535-8","article-title":"Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes","volume":"134","author":"Bramswig","year":"2015","journal-title":"Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vasko, A., Drivas, T.G., and Schrier Vergano, S.A. (2021). Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome. Genes, 12.","DOI":"10.3390\/genes12060937"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1136\/jmedgenet-2018-105625","article-title":"Kabuki syndrome: International consensus diagnostic criteria","volume":"56","author":"Adam","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Castiglioni, S., di Fede, E., Bernardelli, C., Lettieri, A., Parodi, C., Grazioli, P., Colombo, E.A., Ancona, S., Milani, D., and Ottaviano, E. (2022). KMT2A: Umbrella Gene for Multiple Diseases. Genes, 13.","DOI":"10.3390\/genes13030514"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1172\/JCI77435","article-title":"Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes","volume":"125","author":"Yuan","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41576-018-0031-0","article-title":"Diagnosis and management of Cornelia de Lange syndrome: First international consensus statement","volume":"19","author":"Kline","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_40","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_41","first-page":"18-0085","article-title":"Growth hormone deficiency as a cause for short stature in Wiedemann-Steiner Syndrome","volume":"2018","author":"Stoyle","year":"2018","journal-title":"Endocrinol. Diabetes Metab. Case Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000502231","article-title":"Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective","volume":"92","author":"Ambler","year":"2019","journal-title":"Horm. Res. Paediatr."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/10\/1545\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:50:18Z","timestamp":1760143818000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/10\/1545"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,12]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["children9101545"],"URL":"https:\/\/doi.org\/10.3390\/children9101545","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,12]]}}}