Comparisons of intellectual capacities between mild and classic adult-onset phenotypes of myotonic dystrophy type 1 (DM1)

Abstract

BackgroundMyotonic dystrophy type 1 (DM1) is an autosomal dominant genetic multisystem disorder and the commonest adult-onset form of muscular dystrophy. DM1 results from the expansion of an unstable trinucleotide cytosine-thymine-guanine (CTG) repeat mutation. CTG repeats in DM1 patients can range from 50 to several thousands, with a tendency toward increased repeats with successive generations (anticipation). Associated findings can include involvements in almost every systems, including the brain, and cognitive abnormalities occur in the large majority of patients. The objectives are to describe and compare the intellectual abilities of a large sample of DM1 patients with mild and classic adult-onset phenotypes, to estimate the validity of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) in DM1 patients with muscular weakness, and to appraise the relationship of intelligence quotient (IQ) to CTG repeat length, age at onset of symptoms, and disease duration.MethodsA seven-subtest WAIS-R was administered to 37 mild and 151 classic adult-onset DM1 patients to measure their Full-Scale (FSIQ), Verbal (VIQ) and Performance IQ (PIQ). To control for potential bias due to muscular weakness, Standard Progressive Matrices (SPM), a motor-independent test of intelligence, were also completed.ResultsTotal mean FSIQ was 82.6 corresponding to low average IQ, and 82% were below an average intelligence. Mild DM1 patients had a higher mean FSIQ (U=88.7 vs 81.1, p<0.001), VIQ (U=87.8 vs 82.3, p=0.001), and PIQ (U=94.8 vs 83.6, p<0.001) than classic adult-onset DM1 patients. In both mild and classic adult-onset patients, all subtests mean scaled scores were below the normative sample mean. FSIQ also strongly correlate with SPM (rs=0.67, p<0.001), indicating that low intelligence scores are not a consequence of motor impairment. FSIQ scores decreased with both the increase of (CTG)n (rs=−0.41, p<0.001) and disease duration (rs=−0.26, p=0.003).ConclusionsResults show that intellectual impairment is an extremely common and important feature in DM1, not only among the classic adult-onset patients but also among the least severe forms of DM1, with low IQ scores compared to general reference population. Health care providers involved in the follow-up of these patients should be aware of their intellectual capacities and should adapt their interventions accordingly.

Myotonic dystrophy: disease repeat range, penetrance, age of onset, and relationship between repeat size and phenotypes

“…Cardiac conduction defects with arrhythmias contribute to the shortened life span of adult DM1 patients [61] [62]. Mild intellectual deficits can be found in both of adult and late-onset patients [•63], but clinical depression and personality disorders are more common in adult DM1 [64] [65]. Nocturnal apnoeic episodes and excessive daytime somnolence also have significant repercussions on the quality of adult DM1 patient’s life [66] [67].…”

Diagnosis and management of adult hereditary cardio-neuromuscular disorders: A model for the multidisciplinary care of complex genetic disorders

“…Patients classically have a 6 narrow, droopy-appearing face with temporal wasting, frontal balding, and ptosis, and often go on to develop dysarthria, dysphagia, and diaphragmatic weakness in addition to early foot drop and hand weakness. Other important systemic features of DM1, though often variable and incomplete in their appearance, include intellectual impairment, early cataracts, insulin resistance, sleep disordered breathing and excessive daytime sleepiness, and increased risk of cancer [4,8].…”

Uncovering health and social care needs among myotonic dystrophy patients

“…6,8 The wide range (53-106) illustrates the well-described heterogeneity of DM1 patients' intellectual capacities. 6,8 The wide range (53-106) illustrates the well-described heterogeneity of DM1 patients' intellectual capacities.…”

“…In our sample, the full-scale IQ levels were lower than in the normal population, which agrees with previous studies. 6,8 The wide range (53-106) illustrates the well-described heterogeneity of DM1 patients' intellectual capacities. 6,8 However, no correlation was found between unmet needs and IQ, including subscales, suggesting that IQ cannot be used to predict whether DM1 patients have unmet needs or not.…”

“…Neuropsychiatric symptoms and characteristic cognitive profiles, for instance impaired executive function and global cognitive impairment, are considered part of the disease. [6][7][8] DM1 patients may have reduced self-awareness, 9,10 and cognitive dysfunction which may increase over time. 11,12 The complex nature of DM1 results in various levels of disability, and for many, reduced social participation and independence.…”