Akademik Veri Yönetim Sistemi
Turkish archives of pediatrics (Online), cilt.60, sa.2, ss.191-199, 2025 (ESCI)
Objective: Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder caused by EFNB1 pathogenic variants. It is characterized by coronal synostosis, facial asymmetry, hypertelorism, bifid nasal tip, woolly hair, longitudinal nail ridging, and skeletal anomalies in heterozygous females. Hemizygous males paradoxically display a less severe phenotype. This study aims to further define the clinical and mutational spectrum of CFNS in 8 new families. Materials and Methods: Nine female and 2 male patients were included. After detailed phe- notypic characterization, Sanger sequencing of EFNB1 was performed, followed by deletion– duplication analysis of mutation-negative patients. Results: Universal findings in affected females included wide nasal bridge, hypertelorism, and nasal tip abnormalities. Clinical features were consistent with literature data in the majority, except for 2 females with a mild phenotype resembling hemizygous males. Rare or previ- ously undescribed features included enlarged cisterna magna, nasolacrimal duct obstruction, mesoaxial polydactyly, small echogenic kidney, and hypoplastic labia minora in females, and metopic groove, columellar skin pit, and absent midline mustache hair in males. Genetic analy- ses identified 6 EFNB1 variants, including a novel variant, heterozygous in females and hemizy- gous in males. One female patient with a classical CFNS phenotype had no identifiable EFNB1 variant. Conclusion: This study of the largest CFNS cohort from Türkiye expands the phenotypic spec- trum in affected males and females and contributes to the genetic landscape of EFNB1 vari- ants. Two females of the cohort with a phenotype at the mildest end of the CFNS spectrum emphasize the importance of recognizing atypical CFNS presentations for timely diagnosis and accurate genetic counseling.