First Korean Patients with Craniofrontonasal Syndrome Confirmed by EFNB1 Analysis

Craniofrontonasal syndrome (CFNS) is a very rare genetic disorder with variable clinical phenotypes, including brachycephaly, hypertelorism, and a bifid nasal tip. Moreover, longitudinal splittings of the nails and skeletal abnormalities may accompany this condition. CFNS is inherited in an X-linked dominant manner; however, affected heterozygous females exhibit additional and more severe manifestations compared with affected hemizygous males, paradoxically. Here, we report for the first time in Korea two girls with molecularly confirmed CFNS. They commonly showed the typical craniofacial manifestations of CFNS, whereas the severity and the type of associated anomalies differed between them, suggesting phenotypic diversity for this disease. One patient showed unilateral coronal synostosis, cleft palate, and septate uterus together with intellectual disability. The other patient exhibited bilateral coronal synostosis and normal developmental milestones, without anomalies in other organs. A Sanger sequencing analysis of these patients revealed one novel (IVS2+3G>T) and one previously reported mutation (p.Gly151Ser) in EFNB1 Both patients were de novo cases without a family history of CFNS.