Independent coexistence of diseases in neurogenetics: case reports and literature review

Abstract

Combined hereditary pathology (“double trouble”) in a patient and/or family, previously considered a rarity, is being identified increasingly often due to the development of modern genetic diagnostic methods. We describe 13 patients from 12 families with two hereditary diseases of the nervous system, verified by DNA analysis. The spectrum of diseases includes 23 nosological forms, including a number of rare ones. The cases differ in their diagnostic pathways (clinical diagnoses of two diseases and their laboratory confirmation; an unusual clinical presentation of the first disease followed by a targeted search for the second; unexpected findings during molecular genetic testing) and DNA analysis methods (massive parallel sequencing: panel, whole-exome and whole-genome sequencing; targeted methods: sequencing of individual genes and testing for common pathogenic variants; molecular cytogenetic methods). Among the identified gene variants, 8 have not been previously described. The cases are discussed in comparison with literature data on neurogenetic “double troubles”.