Pathogenetic insights from quantification of the cerebriform connective tissue nevus in Proteus syndrome

Background The plantar cerebriform connective tissue nevus (CCTN) is the most common and problematic cutaneous manifestation of Proteus syndrome. Objective To gain insights into CCTN pathogenesis and natural history. Methods The size and location of plantar CCTN was measured on 152 images from 22 individuals with Proteus syndrome by 2 independent, blinded reviewers. Average measures of plantar CCTN were transformed into a linear mixed model to estimate proportionate change in size with age. Results Median patient age was 6.9 years at study onset. The intraclass correlation coefficient between 2 blinded reviewers was 0.946 for CCTN single measures. The CCTN relative area increased with age in children (n = 18, P AKT1 mutant allele frequency was observed (0.62, P  = .10, n = 8). Limitations This was a retrospective review using photographs. Conclusion CCTN growth is affected by age and extent of the CCTN precursor lesion. Monitoring of CCTN size might prove useful for evaluating drug response in the treatment of Proteus syndrome.