Cerebral involvement in myotonic dystrophies

Abstract

Myotonic dystrophy types 1 (DM1) and 2 (DM2) are similar yet distinct autosomal-dominant disorders characterized by muscle weakness, myotonia, cataracts, and multiple organ involvement, including the brain. One key difference between DM1 and DM2 is that a congenital form has been described for DM1 only. Expression of RNA transcripts containing pathogenic repeat lengths produces defects in alternative splicing of multiple RNAs, sequesters specific repeat-binding proteins, and ultimately leads to developmentally inappropriate splice products for a particular tissue. Whether brain pathology in its entirety in adult DM1 and DM2 is caused by interference in RNA processing remains to be determined. This review focuses on the similarities and differences between DM1 and DM2 with respect to neuropsychological, neuropathological, and neuroimaging data relating to cerebral involvement, with special emphasis on the clinical relevance and social consequences of such involvement.

Retentissement des troubles cognitifs sur la vie sociale, professionnelle et émotionnelle des patients dans la forme adulte de la dystrophie myotonique de type I

“…Les troubles cognitifs observés dans la DM1 concernent principalement les fonctions frontales et sont caractérisés par des difficultés exécutives et des troubles de la cognition sociale [2]. Les fonctions exécu-tives interviennent lorsque l'individu doit s'adapter à une situation nouvelle et que les schémas automatiques et routiniers ne sont plus suffisants.…”

“…En plus des symptômes musculaires, le phé-notype comporte des atteintes multisystémiques liées à une expression génétique très variable selon les tissus. Dans la forme adulte, l'atteinte cérébrale est de découverte récente et serait à l'origine de troubles cognitifs chez certains patients [1,2]. Il est fré-quemment décrit des hypersignaux de la substance blanche dont les plus typiques sont au niveau des pôles temporaux (Figure 1).…”

Validation of Sensitivity and Specificity of Tetraplet-Primed PCR (TP-PCR) in the Molecular Diagnosis of Myotonic Dystrophy Type 2 (DM2)

“…9 An important element in the differential diagnosis with DM1 is the absence of congenital forms, which are observed only in DM1 families and which are characterized by polyhydramnios, reduced fetal movements, hypotonia, and respiratory distress at birth, with a high rate of perinatal deaths, developmental delay, and mental retardation. 10 Histological and immunohistochemical studies of DM2 muscles show the dystrophic phenotype with muscle atrophy, nuclear clumps, and type II fibers atrophy.…”

Anterior temporal white matter lesions in adult-form myotonic dystrophy type 1

“…DM1 or Steinert's disease is an autosomal-dominant disorder characterized by muscle weakness and unusual features, compared with other dystrophies, including myotonia, anticipation, and multiple organ involvement 1,2 . Anterior temporal lobe subcortical white matter lesions are described in DM1, but not in DM2 patients 3 .…”