Gökçen Karamık

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.

Koolen‐de Vries syndrome (KdVS) is a rare multisystemic disorder caused by a microdeletion on chromosome 17q21.31 including KANSL1 gene or intragenic pathogenic variants in KANSL1 gene. Here, we describe the clinical and genetic spectrum of eight Turkish children with KdVS due to a de novo 17q21.31 deletion, and report on several rare/new conditions. Eight patients from unrelated families aged between 17 months and 19 years enrolled in this study. All patients evaluated by a clinical geneticist, and the clinical diagnosis were confirmed by molecular karyotyping. KdVS patients had some common distinctive facial features. All patients had neuromotor retardation, and speech and language delay. Epilepsy, structural brain anomalies, ocular, ectodermal, and musculoskeletal findings, and friendly personality were remarkable in more than half of the patients. Hypertension, hypothyroidism, celiac disease, and postaxial polydactyly were among the rare/new conditions. Our study contributes to the clinical spectrum of patients with KdVS, while also provide a review by comparing them with previous cohort studies.