A Phenotypic Description of Congenital Myotonic Dystrophy using PhenoStacks

Background: Congenital Myotonic Dystrophy (CDM1) is a rare neuromuscular condition caused by a triplet repeat expansion in the DMPK gene. Despite there being a well-recognized clinical syndrome, there has not been an effort to use a standardized ontology system to describe the disease characteristics in existing literature. Thus, comparing or contrasting different cohorts from the literature can be challenging, and coding disease features for clinical research or for registry data items is not uniform. PhenoStacks is a visualization analytics tool which helps graphically illustrate phenotypes of patients with genetic disorders using Human Phenotype Ontology (HPO) terms and can sort phenotypes by different disease characteristics. Objective: To demonstrate the efficacy of PhenoStacks and the HPO system as clinical research tools when describing CDM1 cohorts. Methods: Health Endpoints and Longitudinal progression in congenital myotonic dystrophy (HELP-CDM) is an ongoing study which longitudinally follows patients with CDM1. Items from the HELP-CDM data sheet were matched to corresponding HPO terms and analyzed using PhenoStacks. Results: In total 40 subjects' phenotypes were visualized through PhenoStacks and 73 HPO terms were used for the analysis. Frequent phenotypic features included "high narrow palate", "facial palsy", "ptosis", "hyporeflexia", and "weak voice". Contractures were associated with higher repeat sizes. Hypoplastic muscles and infantile axial hypotonia were more frequently observed in infants. Conclusions: PhenoStacks is a valuable clinical and scientific tool as it identifies variability within cohorts and highlights significant phenotypic features.