Yoo Hani, Ko Jung Min, Lim Byung Chan, Cheong Hae Il
Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.
Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea
Ann Clin Lab Sci. 2016 Sep;46(5):544-8.
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.
颅额鼻综合征（CFNS）是一种非常罕见的遗传性疾病，临床表型多样，包括短头畸形、眼距过宽和鼻尖裂。此外，指甲纵向裂开和骨骼异常可能伴随这种情况。CFNS以X连锁显性方式遗传；然而，矛盾的是，与受影响的半合子男性相比，受影响的杂合子女性表现出更多且更严重的症状。在此，我们首次在韩国报告两名经分子确诊的CFNS女孩。她们通常表现出CFNS典型的颅面表现，然而，她们之间相关异常的严重程度和类型有所不同，表明这种疾病存在表型多样性。一名患者表现为单侧冠状缝早闭、腭裂、纵隔子宫以及智力残疾。另一名患者表现为双侧冠状缝早闭且发育里程碑正常，其他器官无异常。对这些患者进行的桑格测序分析在EFNB1基因中发现了一个新突变（IVS2+3G>T）和一个先前报道的突变（p.Gly151Ser）。两名患者均为新发病例，无CFNS家族史。
