Shared facial phenotype of patients with mucolipidosis type IV: A clinical observation reaffirmed by next generation phenotyping.

Abstract

Mucolipidosis type IV (ML-IV) is a rare autosomal-recessive lysosomal storage disease, caused by mutations in MCOLN1. ML-IV manifests with developmental delay, esotropia and corneal clouding. While the clinical phenotype is well-described, the diagnosis of ML-IV is often challenging and elusive. Our experience with ML-IV patients brought to the clinical observation that they share common and identifiable facial features, not yet described in the literature to date. Here, we utilized a computerized facial analysis tool to establish this association. Using the DeepGestalt algorithm, 50 two-dimensional facial images of ten ML-IV patients were analyzed, and compared to unaffected controls (n=98) and to individuals affected with other genetic disorders (n=99). Results were expressed in terms of the area-under-the-curve (AUC) of the receiver-operating-characteristic curve (ROC). When compared to unaffected cases and to cases diagnosed with syndromes other than ML-IV, the ML-IV cohort showed an AUC of 0.822 (p value < 0.01) and an AUC of 0.885 (p value < 0.001), respectively. We describe recognizable facial features typical in patients with ML-IV. Reaffirmed by the DeepGestalt technology, the described common facial phenotype adds to the tools currently available for clinicians and may thus assist in reaching an earlier diagnosis of this rare and underdiagnosed disorder.