ORAL MUCOSAL MICROVASCULAR NETWORK ABNORMALITIES INDE NOVOMUTATION ACHONDROPLASIA

Abstract

Approximately 90% of achondroplasia (ACH) cases are the result of a de novo mutation, with no phenotypical markers for the unaffected ACH parents being known to date. Here, the hypothesis of the presence of an oral mucosal microvascular abnormality in ACH children and unaffected ACH parents was tested. Two-dimensional vascular network geometry was analyzed in 15 children with sporadic ACH, 30 unaffected parents of children with typical ACH phenotype, and 45 control subjects, using high-resolution photographs of the lower gingival and vestibular oral mucosa. The vascular networks of ACH patients and ACH parents exhibited higher D(1–46) (P ≤ 0.013) and D(1–15) (P ≤ 0.0032) fractal dimensions, higher minimum-path dimension (P ≤ 0.0013), higher relative Lempel-Ziv (L-Z) complexity (P < 0.0001), and lower vessel-free area size (P < 0.00001) than controls. A vessel-free area size ≤ 56,832 μm2and L-Z complexity > 0.62 showed 100%-sensitivity and 100%-specificity in identifying unaffected ACH parents. These findings indicate (1) how complexity measures can be used to discover biological differences not demonstrable with traditional measures, and (2) the presence of a previously unrecognized microvascular network abnormality in both ACH patients and unaffected parents of children with de novo mutation ACH.