Cognitive deficits and personality patterns in maternally versus paternally inherited myotonic dystrophy

Abstract

Neuropsychological functioning was compared between 7 myotonic dystrophy (MD) patients with maternal inheritance (mMD), 14 MD patients with paternal (pMD) inheritance, and 10 normal controls. Both groups evidenced slowed performance on a measure of information processing speed. However, the pMD group had an otherwise normal neuropsychological profile. In contrast, the mMD group exhibited abnormal scores on measures of intelligence, visual-construction, and some, albeit not all, measures of frontal functioning. No significant differences between the three groups were detected on measures of verbal or visual memory, or on measures of visual-perception. Overall, these findings suggest that inheritance pattern is one important moderating variable in determining the impact of the MD gene on cognitive functioning. Personality assessment revealed a relatively high incidence of dependent tendencies and depressive symptoms, even among pMDs. Given the generally normal cognitive functioning among pMDs, personality/emotional disturbance observed among MD patients may largely reflect their adjustment to having a progressively disabling medical condition, rather than being a direct expression of MD related brain dysfunction.

Cerebral involvement in myotonic dystrophies

“…Scores on overall IQ as measured by the Wechsler Adult Intelligence Scale (WAIS) are within the normal range in patients with DM1, 11,15,20,87,91,122,132,134 although lower than age-and education-matched controls. In a subset of patients with moderately severe DM1 (CTG range 500 -700), we have found reduced IQ values in one-third of patients irrespective of the degree of muscle disability.…”

Developmental changes in expression of myotonic dystrophy protein kinase in the rat central nervous system

“…It has been suggested that degeneration of the neuronal architecture of the entorhinal cortex destroys a large functional part of hippocampal input and output, resulting in the memory and cognitive deficits associated with Alzheimer's disease (Braak et al, 1993). It is possible that more discrete lesions in the same cells may result in the less drastic abnormalities in memory functions that have been noted in patients with myotonic dystrophy, including nonprogressive abnormalities in immediate recall, abstraction, spatial manipulation, and attention (Harper, 1975(Harper, , 1989Woodward et al, 1982;Bird et al, 1983;Portwood et al, 1984Portwood et al, , 1986Stuss et al, 1987;Censori et al, 1990;Censori et al, 1994;Miller, 1992;Tuikka et al, 1993;Abe et al, 1994;Palmer et al, 1994).…”

“…Stringent psychometric testing (Bird et al, 1983;Tuikka et al, 1993;Palmer et al, 1994) has shown that these defects are most prominent in patients with the neonatal form of myotonic dystrophy, especially if they have inherited the abnormal allele from their mothers (Portwood et al, 1984(Portwood et al, , 1986Palmer et al, 1994) or have large expansions of the trinucleotide repeat in the 3Ј-untranslated region of the DMPK gene (Chang et al, 1993). Because there is an association between maternal inheritance and increased size of the pathognomonic trinucleotide repeat in myotonic dystrophy (Ashizawa et al, 1992), it is possible that the characteristic pattern of CNS defects is most marked in a genotypic subset of patients with the neonatal form of the disease.…”

Saccades and smooth pursuit in myotonic dystrophy

“…Widespread cognitive deficits are reported on formal assessment in MD [2,3,5], including impairment on verbal fluency and other measures of frontal performance [2,33]. Diffuse sub-cortical lesions on computed tomography and magnetic resonance imaging are reported in MD [2,5], and functional imaging studies demonstrate cerebral hypoperfusion, particularly affecting the frontal and temporal lobes [3,34].…”