Background: Mucolipidosis type IV (ML-IV) is a rare autosomal recessive lysosomal storage disease, caused by mutations in the MCOLN1 gene. It manifests with non-specific symptoms of developmental delay, esotropia and even corneal clouding. While the clinical phenotype, molecular basis and underlying pathomechanism have been described, the diagnosis of ML-IV remains elusive and patients are often misdiagnosed. Our clinical observation was that ML IV patients share common and identifiable facial features, which have yet to be included in the clinical phenotype as described in the literature to date.
Objective and methods: In order to validate these findings using an objective and digital tool, two-dimensional facial images of ten patients with ML-IV, obtained at various ages, were analyzed using facial dysmorphology novel analysis (FDNA). This technology utilizes various measurements extracted from automatically-detected facial points from facial photographs, to recognize distinct dysmorphic features and analyze their similarities to known facial patterns, termed gestalts.
Results: When analyzed in comparison to a control cohort of unaffected cases (n=100) and a cohort of cases diagnosed with syndromes other than ML-IV (n=100), the ML-IV cohort showed a mean area-under-the-curve (AUC) of 0.77 (SD, 0.19) and 0.87 (SD, 0.05), respectively.
Conclusions: We describe for the first time recognizable facial features typical in patients with ML-IV. Reaffirmed by the objective FDNA technology, the described common facial gestalt adds to the tools currently available for clinicians and may thus assist in reaching an earlier diagnosis of this rare and underdiagnosed disorder.
