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3 M syndrome is a well-known autosomal recessive skeletal genetic disorder caused by biallelic pathogenic variants in the CUL7, OBSL1, and CCDC8 genes. Affected individuals exhibit profound pre- and postnatal growth retardation, distinctive facial features with normal intelligence. This study aims to provide insight into the comprehensive evaluation of clinical, laboratory, and radiological findings, expand the mutational spectrum of the disease, and establish a genotype-phenotype correlation in the present cases. A total of 25 patients from 19 unrelated families were included in the study. Genetic etiology was determined in probands through the utilization of Sanger sequencing and/or targeted gene panel analysis. The clinical, laboratory, and genetic features of all patients at admission and during follow-up were documented. Genotype-phenotype correlation was carried out in the CUL7 and OBSL1 groups. The genetic etiology was established in all patients (n = 25/25, 100%). We identified 15 distinct variants in CUL7, OBSL1, and CCDC8 genes, with eleven being novel. CUL7 variants were present in 13 patients (n = 13/25, 52%), while OBSL1 variants were found in 11 patients (n = 11/25, 44%). No notable distinctions were found in mean birth weight, height, and standard deviation scores between the CUL7 and OBSL1 mutation groups (p > 0.05). Patients with CUL7 variants exhibited significantly lower height standard deviation scores both at admission and at the last examination, as well as lower weight standard deviation scores at the last examination, compared to those with OBSL1 variants (p < 0.05)., Conclusion: To date, genotype-phenotype correlations have been identified in a limited number of studies. Further research involving larger cohorts is necessary to solidify these correlations., What Is Known: • 3M syndrome is a well-known skeletal dysplasia caused by biallelic pathogenic variants in CUL7, OBSL1, and CCDC8 genes. • Despite genetic heterogeneity, clinical, and radiologic features show homogeneity in affected individuals., What Is New: • Genotype-phenotype correlations have been established in limited studies. • The CUL7 group exhibited significantly lower height SDS at both admission and the final evaluation and lower weight SDS at the final examination compared to the OBSL1 group. • The frequency of variants in the OBSL1 gene among Turkish patients exceeds the rates reported in the literature. • Gradenigo syndrome is being reported for the first time in a patient with 3M syndrome., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by Health Sciences, Diyarbakir Gazi Yasargil Training and Research Hospital Noninvasive Clinical Research Ethical Committee (approval number: 2024/69). Consent to participate: Written informed consent was obtained from the parents. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To evaluate the utility of genetic testing for etiology-specific diagnosis (ESD) in infantile epileptic spasms syndrome (IESS) with a step-based diagnostic approach in the next-generation sequencing (NGS) era., Methods: The study cohort consisted of 314 patients with IESS, followed by the Pediatric Neurology Division of Ege University Hospital between 2005 and 2021. The ESD was evaluated using a step-based approach: step I (clinical phenomenology), step II (neuroimaging), step III (metabolic screening), and step IV (genetic testing). The diagnostic utility of genetic testing was evaluated to compare the early-NGS period (2005 to 2013, n = 183) and the NGS era (2014 to 2021, n = 131)., Results: An ESD was established in 221 of 314 (70.4%) infants with IESS: structural, 40.8%; genetic, 17.2%; metabolic, 8.3%; immune-infectious, 4.1%. The diagnostic yield of genetic testing increased from 8.9% to 41.7% in the cohort during the four follow-up periods. The rate of unknown etiology decreased from 34.9% to 22.1% during the follow-up periods. The genetic ESD was established as 27.4% with genetic testing in the NGS era. The genetic testing in the NGS era increased dramatically in subgroups with unknown and structural etiologies. The diagnostic yields of the epilepsy panels increased from 7.6% to 19.2%. However, the diagnostic yield of whole exome sequencing remained at similar levels during the early-NGS period at 54.5% and in the NGS era at 59%., Conclusions: The more genetic ESD (27.4%) was defined for IESS in the NGS era with the implication of precision therapy (37.7%)., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work., (Copyright © 2024. Published by Elsevier Inc.)