Dual molecular diagnoses in a neurometabolic specialty clinic.

Reports of patients with concomitant diagnoses of two inherited genetic disorders, sometimes referred to as "double trouble," have appeared intermittently in the medical literature. We report eight additional cases with dual diagnoses of two genetic conditions. All cases had a phenotype atypical for their primary diagnosis, leading to the search for a second genetic diagnosis. These cases highlight the importance of the history, physical examination and continued work-up if the phenotype of the patient falls drastically outside what has been reported with their primary diagnosis. Some of the diagnoses of the patients presented here (e.g., Myotonic Dystrophy Type 1, fascioscapulohumeral muscular dystrophy) would not have been identified by genetic testing done on a next generation sequencing backbone (e.g., panel or exome sequencing). When the clinical picture is atypical or more severe than expected the possibility of a dual diagnosis (double trouble) should be considered. Identification of a second genetic condition can impact management and genetic counseling.

A mitochondrial disorder with ptosis and exercise intolerance without ophthalmoparesis secondary to m.5865 T > C variant.

We describe a novel mitochondrial variant (m.5865 T > C) in a patient with decreased exercise endurance and juvenile onset slowly progressive bilateral ptosis without ophthamloparesis. The m.5865 T > C variant was seen in 82.9% of mtDNA molecules in skeletal muscle tissue and ~8% of mtDNA molecules in urine epithelium, but was not detected in blood leukocytes. The proband does not demonstrate any additional features often seen in individuals with a mitochondrial disorder (i.e., sensorineural hearing loss, type 2 diabetes, stroke-like episodes, muscle weakness, ophthalmoparesis, cardiomyopathy or cardiac arrhythmias). This case suggests that ptosis and exercise intolerance, without ophthalmoparesis, are the primary clinical features of the m.5865 T > C mtDNA variant.