Craniofacial phenotype in Cutis Laxa

Cutis laxa (CL) is a rare connective tissue disorder associated with mutations in extracellular matrix genes that leads to loose, redundant, lax skin and is often accompanied by cardiovascular, pulmonary, musculoskeletal or neurological complications. Literature suggests that individuals with CL have distinctive craniofacial features. Prior reports have been inconsistent and to date no quantitative, objective analysis of the craniofacial phenotype has been carried out on this population. To address this deficit, state-of-the-art 3-dimensional (3D) imaging was used to capture quantitative facial measurements in a sample of individuals with cutis laxa and compare the facial morphology of affected individuals to matched controls. The hypothesis that different forms of CL (acquired vs congenital) exhibit different craniofacial phenotypes was also tested. Subjects were recruited as part of the Genetics of Extracellular Matrix in Health and Disease Study and 3D images of the head and face were acquired using a 3DMD portable stereophotogrammetry system. Twenty-four facial landmarks were identified on each subject’s 3D facial image, and from these landmarks, a set of standard anthropometric facial measurements was calculated. These shape coordinates were then subjected to principal components analysis to quantify and compare the major aspects of facial shape variation within and among groups. Congenital CL showed marked narrowing and lengthening of the face and subjects with ELN mutations had the most severe facial phenotypes. The craniofacial shape did not correlate with the individual’s skin elasticity supporting the conclusion that the craniofacial phenotype of CL is primarily caused by altered craniofacial development rather than skin laxity. The public health significance of this study is that craniofacial dysmorphism can occur as a part of many genetic syndromes. This type of quantitative study can be applied to any genetic disease with a distinct craniofacial phenotype and may assist the development of accurate, objective, sensitive and specific diagnostic criteria.