Craniofrontonasal dysplasia

Craniofrontonasal dysplasia (CFND), also known as craniofrontonasal syndrome, is a rare genetic disorder characterized by distinctive abnormalities of the skull, face, and other body structures. The condition is caused by mutations in the EFNB1 gene located on the X chromosome, which encodes ephrin-B1, a protein important for cell signaling during embryonic development. Paradoxically, despite being X-linked, females are typically more severely affected than males, a phenomenon explained by cellular interference — in heterozygous females, random X-inactivation creates a mosaic of cells expressing normal and mutant ephrin-B1, disrupting cell-cell communication at tissue boundaries. Key clinical features include coronal craniosynostosis (premature fusion of skull sutures), a wide nasal bridge with a bifid or broad nasal tip, widely spaced eyes (hypertelorism), frontal bossing, and a widow's peak hairline. Additional features may include thick, wiry or curly hair, longitudinal ridging or splitting of the nails, asymmetry of the face or limbs, sloping shoulders, and skeletal anomalies such as syndactyly (webbing of fingers or toes). Some individuals may have mild intellectual disability, though cognitive development is often normal. The body systems primarily affected include the craniofacial skeleton, the limbs, and the skin and its appendages. Treatment of craniofrontonasal dysplasia is symptomatic and supportive, typically requiring a multidisciplinary approach. Surgical intervention is often necessary to correct craniosynostosis, hypertelorism, and other craniofacial abnormalities, and may involve staged procedures over childhood and adolescence. Syndactyly and other limb anomalies may also require surgical correction. Genetic counseling is recommended for affected families. With appropriate management, the prognosis is generally favorable, and life expectancy is typically normal.

Common questions about Craniofrontonasal dysplasia