Background: Myotonia congenita is the most common form of nondystrophic myotonia and is caused by Mendelian inherited mutations in the CLCN1 gene encoding the voltage-gated chloride channel of skeletal muscle. Objective: The study aimed to describe the clinical and genetic spectrum of Myotonia congenita in a large pediatric cohort. Methods: Demographic, genetic, and clinical data of the patients aged under 18 years at time of first clinical attendance from 11 centers in different geographical regions of Türkiye were retrospectively investigated. Results: Fifty-four patients (mean age:15.2 years (±5.5), 76% males, with 85% Becker, 15% Thomsen form) from 40 families were included. Consanguineous marriage rate was 67%. 70.5% of patients had a family member with Myotonia congenita. The mean age of disease onset was 5.7 (±4.9) years. Overall 23 different mutations (2/23 were novel) were detected in 52 patients, and large exon deletions were identified in two siblings. Thomsen and Becker forms were observed concomitantly in one family. Carbamazepine (46.3%), mexiletine (27.8%), phenytoin (9.3%) were preferred for treatment. Conclusions: The clinical and genetic heterogeneity, as well as the limited response to current treatment options, constitutes an ongoing challenge. In our cohort, recessive Myotonia congenita was more frequent and novel mutations will contribute to the literature.

Cardiofaciocutaneous (CFC) syndrome is one of the developmental disorders caused by a dysregulation of the Ras/mitogen-activated protein kinase (MAPK) pathway. RASopathies share overlapping clinical features, making the diagnosis challenging, especially in the newborn period. The majority of CFC syndrome cases arise by a mutation in the BRAF, MAP2K1, MAP2K2, or (rarely) KRAS genes. Germline KRAS mutations are identified in a minority of CFC and Noonan syndrome cases. Here, we describe a patient with a KRAS mutation presenting with a CFC syndrome phenotype. The female patient was referred for genetic testing because of congenital exophthalmos. Her facial appearance is distinctive with a coarse face, exophthalmos, ptosis, downslanting palpebral fissures, hypertelorism, deep philtrum, downturned corners of the mouth, and a short neck. She suffered from feeding difficulties, poor weight gain, and developmental delay. The sequencing of the genes involved in the MAPK pathway (PTPN11, SOS1, RAF1, KRAS, NRAS, MAP2K1, SHOC2, CBL, and SPRED1) identified a heterozygous de novo NM_004985.4:c.173C>T (p.Thr58Ile) in the KRAS gene. Germline KRAS mutations have been identified in approximately 2% of the reported NS cases and less than 5% of the reported CFC syndrome cases. Because CFC and Noonan syndrome share clinical overlapping features, the phenotype caused by KRAS mutations is often difficult to assign to one of the 2 entities. The mutation that we detected in our patient was previously reported in a patient with an Noonan syndrome phenotype. However, our patient predominantly exhibits CFC clinical features. In our case, coarse facial appearance and severe developmental delay help discriminate CFC from Noonan syndrome. Thus, patient follow-up, especially for delayed motor milestones suspected from RASopathies, is important for the discrimination of overlapping conditions as in the abovementioned syndromes.

Objective: Maturity‐onset diabetes of the young (MODY) represents a genetically and clinically heterogeneous form of monogenic diabetes caused by defects in pancreatic β‐cell function. Accurate molecular diagnosis is essential for distinguishing MODY from type 1 and type 2 diabetes, enabling precision‐based management and targeted therapy. This study aimed to evaluate the genetic and clinical features of pediatric patients with MODY, to assess the prevalence of common and rare subtypes, and to report novel pathogenic variants identified in a Turkish cohort. Methods: This single‐center, retrospective cohort study evaluated 81 pediatric patients with suspected MODY followed between 2022 and 2025. Genetic analysis was performed using targeted next‐generation sequencing (NGS) panels, including HNF4A , GCK , HNF1A , PDX1 , HNF1B , NEUROD1 , INS , ABCC8 , KCNJ11 , APPL1 , and CEL . Patients were selected based on the presence of at least two clinical features suggestive of MODY, as defined by the 2022 International Society for Pediatric and Adolescent Diabetes (ISPAD) Clinical Practice Consensus Guidelines. Demographic, biochemical, and clinical data were extracted from hospital records and analyzed descriptively. Results: Genetic variants were identified in 25 of 81 patients (30.9%), including pathogenic, likely pathogenic, and variants of uncertain significance (VUS). Of these, 22 variants were classified as pathogenic or likely pathogenic, corresponding to a diagnostic yield of 27.2%. The most frequently affected gene was GCK (72.0%), followed by HNF1A (8.0%), with single cases identified in HNF1B , INS , PDX1 , CEL , and KCNJ11 . Rare MODY subtypes collectively accounted for 20.0%. Three novel GCK variants c.1055T >C, c.1229A >C, and c.185_186insA were identified. One patient with syndromic features harbored a heterozygous 17q12 microdeletion encompassing HNF1B , approximately 1.5 Mb in size, and presented with global developmental delay, intellectual disability, epilepsy, dysmorphic facial features, persistent hypomagnesemia, and a bicornuate uterus with normal renal structure. Following genetic analysis, two patients had therapy adjustments based on the identified variants. Conclusion: This study underscores the clinical and genetic heterogeneity of MODY in the pediatric population and reinforces the value of comprehensive NGS panels for accurate diagnosis, even in patients who do not fully meet classical MODY criteria. The identification of novel GCK variants and the detection of rare subtypes further expand the mutational and phenotypic spectrum of pediatric monogenic diabetes. These findings highlight the importance of incorporating population‐specific genomic data into clinical practice and of periodically re‐evaluating gene–disease associations as new molecular and functional evidence emerges. Ultimately, the integration of molecular diagnostics into routine pediatric diabetes care will enhance diagnostic yield, optimize management, and improve long‐term outcomes for affected families.

Background: Double genetic diagnoses are increasingly identified with the advent of genome-wide sequencing techniques. While MECP2 mutations are associated with Rett syndrome and EPHB4 mutations with vascular malformation syndromes, their co-occurrence has not been previously described. Case Presentation: We describe an 8-year-and-2-month-old girl presenting with global developmental delay, autism spectrum disorder, and stereotypic behaviors, along with multiple well-demarcated cutaneous vascular lesions. Although she had no clinical seizures, electroencephalogram revealed epileptiform discharges. Physical examination showed dysmorphic features and vascular anomalies, including telangiectatic pink-to-red macular vascular lesions. Whole exome sequencing (WES) identified two de novo heterozygous pathogenic variants: a missense mutation in MECP2 (c.433C>T; p.Arg145Cys), a gene classically implicated in Rett syndrome, and a nonsense mutation in EPHB4 (c.1093C>T; p.Arg365Ter), which has been previously associated with capillary malformation-arteriovenous malformation syndrome type 2. The neurodevelopmental findings, while consistent with the broader spectrum of MECP2-related disorders, along with coexisting vascular anomalies, were best accounted for by a dual genetic diagnosis involving both MECP2 and EPHB4. Conclusion: This case underscores the diagnostic value of considering dual genetic diagnoses in patients with complex phenotypes and highlights the role of WES in uncovering multilocus variation, thereby expanding the known phenotypic spectrum associated with MECP2 and EPHB4 mutations.