Artificial intelligence (AI) is increasingly applied in diagnostic imaging to enhance pattern recognition and support clinical decision-making. In 2024, Google introduced Med-Gemini-3D, a multimodal platform capable of interpreting 3-dimensional computed tomography scans and generating radiologist-level reports. Although not yet approved for independent clinical use, such systems may assist in identifying rare conditions that are unfamiliar to clinicians. The authors describe a 22-month-old girl who presented with persistent bilateral parietal skull defects and global developmental delay. Computed tomography demonstrated symmetric ossification defects adjacent to the sagittal suture that were not initially recognized by the treating physician. The patient's mother used a smartphone application powered by Med-Gemini-3D to analyze a 3D-CT reconstruction image, which suggested a diagnosis of "Catlin mark skull," a historical term for Enlarged Parietal Foramina (EPF). This prompted genetic evaluation and identification of a CDC42BPB variant associated with Chilton-Okur-Chung neurodevelopmental syndrome-a finding not previously reported in association with EPF. Establishing the diagnosis facilitated earlier therapeutic interventions and informed long-term management. This case underscores the potential role of AI-assisted tools in recognizing rare craniofacial anomalies. While such technologies cannot replace clinical expertise and remain limited by variable accuracy, they may help expand differential diagnoses, expedite referrals, and improve outcomes through earlier intervention. Continued research is needed to validate their reliability and to define their optimal integration into clinical practice.

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. 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. • 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. • 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.

Okur-Chung Neurodevelopmental Syndrome (OCNDS) is an ultra-rare genetic disorder caused by de novo mutations in the CSNK2A1 gene, which encodes the catalytic subunit of protein kinase CK2α. OCNDS is characterized by global developmental delay, intellectual disability, speech and language deficits, and other multi-system symptoms. Although prior reports have described considerable phenotypic variability, the relationship between specific CK2α variant locations and symptom presentation remains poorly defined. We analyzed natural history data from 48 individuals with pathogenic or likely pathogenic CSNK2A1 missense variants enrolled in Simons Searchlight. Variants were categorized by their location in conserved CK2α protein domains, specifically distinguishing between loop (e.g., glycine-rich loop, p+1 loop) and non-loop regions. We evaluated symptom burden across organ systems, age at diagnosis, and adaptive functioning using caregiver-reported surveys. All individuals reported speech/language delay, with additional common features including global developmental delay, neurological symptoms, and gastrointestinal issues. Variants in loop regions were associated with significantly younger age at diagnosis and a higher frequency of hypotonia. Mutations in the glycine-rich loop-known to bind both ATP and the regulatory CK2β subunit-were linked to significantly higher symptom burden and more non-seizure neurological symptoms. No significant differences were observed between variant locations for core features such as sleep issues, intellectual disability, or speech delay.. Our findings suggest a core OCNDS symptom profile that is conserved across genotypes, with loop-region variants contributing to increased symptom burden. These results reinforce the relevance of conserved functional domains in driving phenotype severity and support the use of mutation location as a potential biomarker to stratify patients for therapeutic prioritization. Further studies incorporating functional assays and larger cohorts are needed to elucidate mechanisms of variant-specific pathogenesis and guide personalized intervention strategies.

This case discusses the limits of neurodevelopmental functioning attributable to Duchenne's Muscular Dystrophy (DMD) dysfunction. A 3-year-old male presented with global developmental delay, growth failure, and dysmorphic facial features. An SNP microarray revealed an interstitial duplication in exon 55 of DMD suggestive of Becker Muscular Dystrophy (BMD), but his degree of delays led to follow-up exome sequencing revealing a pathogenic CSNK2A1 variant diagnostic for Okur-Chung Neurodevelopmental Syndrome. Large cohorts predict a full-scale IQ (FSIQ) of 88.3 ± 13.9 among all patients with BMD and 86.1 ± 15.0 among all patients with DMD, while variants impacting the brain dystrophin isoform Dp140 are associated with FSIQ of 77.7 ± 10.8 in BMD and 78.8 ± 18.6 in DMD. An FSIQ one standard deviation below these expected ranges should prompt screening for alternative causes of neurodevelopmental delays, and an FSIQ two standard deviations below these ranges should prompt broad-spectrum genetic testing.

To investigate the clinical features and genetic etiology of one child with Okur-Chung neurodevelopmental syndrome (OCNDS). The pathogenic variation spectrum of the CSNK2A1 gene and the phenotype spectrum of OCNDS were analyzed retrospectively. A patient was selected from the endocrinology department of Dongying People's Hospital in July 2024. The genetic etiology of the phenotypic abnormality was identified by whole-exome sequencing (WES). All previously reported cases of OCNDS were retrieved from China National Knowledge Infrastructure (CNKI), Wanfang Data, PubMed, and the ClinVar database, and the phenotype and pathogenicity of the CSNK2A1 gene were retrospectively summarized. The differences in the mutation location and clinical phenotype of the CSNK2A1 gene were analyzed in combination with the literature on cell and molecular genetics. One variant (NM_001895.4: c.149A>G:p.Tyr50Cys) were de novo and previously reported within the CSNK2A1 gene and has been identified as a potential cause of OCNDS. The clinical data of 65 patients with OCNDS were retrospectively analyzed. The main clinical characteristics of OCNDS were developmental retardation of the nervous system, intellectual disability, facial deformity, language disorder, and other system abnormalities. This specific variant is located within the Glycine-Rich loop domain. There were significant differences in sleep disorders, autism spectrum disorders, short stature, and developmental delays. This study diagnosed an OCNDS patient caused by a heterozygous mutation NM_001895.4: c.149A>G:p.Tyr50Cys in the CSNK2A1 gene through exome sequencing technology, further expanding the pathogenic variant spectrum of this gene. A systematic literature review and analysis was conducted to provide a foundation for the subsequent demonstration, which was based on the findings of the review. The demonstration revealed that variants in critical residues within the kinase domain disrupt the protein's spatial conformation and impair its function. This provides molecular evidence for genotype-phenotype correlation. These findings contribute to the advancement of knowledge in the field of OCNDS pathogenesis and provide a foundation for the development of genetic counselling and targeted therapeutic interventions.