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. 2025 Jul 30;184(8):512.
doi: 10.1007/s00431-025-06347-7.

Clinical and molecular results in 15 Turkish patients with Wiedemann-Steiner syndrome: identification of eight novel KMT2A variants and a case of dual molecular diagnosis in the CSNK2A1

Burcu Yeter  1 , Yasemin Kendir Demirkol  2 , Esra Usluer  2 , Sümeyra Oğuz  3 , Metin Eser  4 , Murat Hakkı Yarar  4 , Sezin Canbek  4 , Batın Ilgıt Sezgin  5 , Akçahan Akalın  6 , Gökçen Karamık  7 , Enise Avci Durmuşalioğlu  8   9 , Zeynep Ocak  10 , Mutlu Karkucak  11 , Nuray Öztürk  12 , Funda Kökali  13 , Şirin Sedef Baş  13 , Sermin Özcan  14 , Banu Nur  15 , Ercan Mıhçı  15 , Nursel H Elcioglu  13   16
Affiliations

Clinical and molecular results in 15 Turkish patients with Wiedemann-Steiner syndrome: identification of eight novel KMT2A variants and a case of dual molecular diagnosis in the CSNK2A1

Burcu Yeter et al. Eur J Pediatr. .

Abstract

Wiedemann-Steiner syndrome (WSS) is a rare autosomal dominant neurogenetic disorder caused by monallelic variants in KMT2A gene, characterized by neuromotor developmental delay, intellectual disability, microcephaly, seizures, behavioral disorders, dysmorphic facial features, hirsutism, and systemic anomalies. The KMT2A gene encodes a histone lysine methyltransferase crucial for the regulation of gene expression during early developmental stages. In this study, the clinical and molecular findings of 15 Turkish patients with WSS confirmed by whole exome sequencing are reported. Variant segregation was confirmed in all families. The ages of the patients were between 1.5 and 16 years. The majority of patients had neuromotor developmental delay, speech delay, and intellectual disability. The most frequently recognised dysmorphic facial features were thick eyebrows, long eyelashes, synophrys, hypertelorism, and broad nose. Other frequently observed clinical findings included short stature, congenital hypotonia, behavioral problems, genitourinary anomalies, and abnormal gait. Novel findings included focal segmental glomerulosclerosis, cholelithiasis, and sacrococcygeal teratoma. Fifteen different KMT2A variants were detected, including 8 novel (p.Gln3594*, p.Glu1407Argfs*4, p.Ser610Ilefs*9, p.Ser2188Leufs*25, p.Glu970Glnfs*37, p.Ser759Valfs*22, p.Lys1346Serfs*24, and c.11146 + 1_11146 + 6delinsA) variants. Additionally, one patient exhibited a dual molecular diagnosis with a de novo variant in CSNK2A1, associated with Okur-Chung neurodevelopmental syndrome.

Conclusion: This study expands the clinical and molecular spectrum of WSS, highlighting novel variants and unique manifestations. It emphasizes the importance of molecular testing in accurate diagnosis and management. By characterizing phenotypic diversity and dual diagnosis, this work contributes valuable insights for advancing clinical care and guiding future research.

What is known: • Wiedemann-Steiner syndrome (WSS) is a rare neurodevelopmental disorder caused by heterozygous KMT2A variants, characterized by developmental delay, intellectual disability, and distinctive facial features. • WSS exhibits marked clinical variability among affected individuals.

What is new: • This study presents the largest Turkish WSS cohort to date, expands the phenotypic spectrum with novel findings such as focal segmental glomerulosclerosis, cholelithiasis, and sacrococcygeal teratoma. • This study presents the largest Turkish WSS cohort to date and expands the phenotypic spectrum with novel findings such as focal segmental glomerulosclerosis, cholelithiasis, and sacrococcygeal teratoma, while also identifying eight novel WSS-associated variants, including p.Gln3594*, p.Glu1407Argfs*4, p.Ser610Ilefs*9, p.Ser2188Leufs*25, p.Glu970Glnfs*37, p.Ser759Valfs*22, p.Lys1346Serfs*24, and c.11146+1_11146+6delinsA.

Keywords: CSNK2A1; Intellectual disability; KMT2A; Neurodevelopmental delay; Wiedemann-Steiner syndrome.

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Conflict of interest statement

Declarations. Ethics approval: The study complied with the Declaration of Helsinki and received approval from the Ethical Committee of Umraniye Training and Research Hospital (approval number: B.10.1.TKH.4.34.H.GP.0.01/233, date: 01/08/2024). Informed consent: The authors affirm that human research participants provided informed consent for publication of the images in Figs. 1 and 2. Competing interests: The authors declare no competing interests.

References

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