Revisiting Wiedemann-Steiner Syndrome: Novel KMT2A Variants and Broadened Clinical Spectrum
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: . Although several large international cohorts have helped define its broad clinical spectrum, data from underrepresented populations remain limited. Aims: To characterize the molecular and phenotypic spectrum of Turkish patients with WDSTS and compare these findings with previously published cohorts. Study Design: Multicenter retrospective cohort study. Methods: Sixteen individuals from 15 unrelated families were recruited across Türkiye. Clinical information was obtained through medical records and systematic phenotyping. Molecular analyses included next-generation sequencing or targeted variant testing, and the variants were classified according to the American College of Medical Genetics and Genomics guidelines. Results: variants were identified, including nine novel alleles. Most variants were predicted to result in loss of function; only one was a missense substitution. Neurodevelopmental involvement was prominent, with developmental and speech delays, intellectual disability, and behavioral comorbidities such as autism spectrum disorder and attention-deficit/hyperactivity disorder. Endocrine evaluation revealed growth hormone deficiency in approximately half of the tested patients. Ophthalmologic, cardiac, and dental abnormalities, including delayed tooth eruption, further expanded the known phenotype. Additional systemic features included skeletal, genitourinary, and immunological findings. Comparison with previously reported cohorts displayed no statistically significant genotype-phenotype correlations, although truncating variants appeared to be associated with more pronounced neurodevelopmental and behavioral manifestations. Conclusion: as a key chromatin regulator and an "umbrella gene" within the chromatinopathy spectrum. Growing recognition of these disorders underscores the need for systematic, multidisciplinary surveillance and contributes to the expanding global understanding of their shared pathogenic mechanisms.
Source: Balkan Medical Journal
Authors: Zehra Manav Yiğit, Aydan Mengübaş Erbaş, Ayberk Türkyılmaz, İsmihan Merve Tekin, Elif Yılmaz Güleç, Gülsüm Kayhan, Aydeniz Aydın Gümüş, Esra Arslan Ateş, Eyyüp Üçtepe, Kübra Ateş, Elvin Kazancıoğlu, Bülent Uyanık, Sena Çetin, Sahra Acır, Elif Sobu, İbrahim Kamer, Ahmet Yeşilyurt, Alperhan Çebi, Ahmet Anık, Müge Ayanoğlu, Gül Ünsel Bolat, Gökay Bozkurt, Hilmi Bolat
Institutions: Adnan Menderes University, Karadeniz Technical University, Istanbul Medeniyet University, Gazi University, Sağlık Bilimleri Üniversitesi, İstanbul Başakşehir Çam ve Sakura Şehir Hastanesi, Istanbul University-Cerrahpaşa, Istanbul University, Sakarya Eğitim ve Araştırma Hastanesi, Adıyaman Eğitim ve Araştırma Hastanesi, Bezmiâlem Vakıf Üniversitesi, Üsküdar University, Balıkesir University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4416736205
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