Psychiatric and cognitive phenotype of childhood myotonic dystrophy type 1

Abstract

ABBREVIATIONSASD Autism spectrum disorder CTG Cytosine-thymine-guanine DM1 Myotonic dystrophy type 1 AIM To investigate the psychiatric and cognitive phenotype in young individuals with the childhood form of myotonic dystrophy type 1 (DM1).METHOD Twenty-eight individuals (15 females, 13 males) with childhood DM1 (mean age 17y, SD 4.6, range 7-24y) were assessed using standardized instruments and cognitive testing of general intelligence, visual attention, and visual-spatial construction abilities.RESULTS Nineteen patients had repeated a school grade. The mean (SD) Full-scale IQ was 73.6 (17.5) and mean Verbal IQ was significantly higher than the mean Performance IQ: 80.2 (19.22) versus 72.95 (15.58), p=0.01. Fifteen patients had one or more diagnoses on the DSM-IV axis 1, including internalizing disorders (phobia, n=7; mood disorder, n=6; other anxiety disorders, n=5) and attention-deficit-hyperactivity disorder, inattentive subtype (n=8). Twelve out of 22 patients had alexithymia (inability to express feelings with words and to recognize and share emotional states). Cognitive testing found severe impairments in visual attention and visual-spatial construction abilities in four out of 18, and 14 out of 24 patients respectively. No diagnosis was correlated with the transmitting parent's sex or with cytosine-thymine-guanine (CTG) repeat numbers. Patients with severe visual-spatial construction disabilities had a significantly longer CTG expansion size than those with normal visual-spatial abilities (p=0.04).INTERPRETATION Children and adolescents with childhood DM1 have frequent diagnoses on DSM-IV axis 1, with internalizing disorders being the most common type of disorder. They also have borderline low intelligence and frequent impairments in attention and visual-spatial construction abilities.Myotonic dystrophy type 1 (DM1) is the most frequently inherited neuromuscular disease, with autosomal dominant transmission. The estimated incidence is one in 8000 people.1 DM1 is a progressive neuromuscular disorder caused by the expansion of a cytosine-thymine-guanine (CTG) trinucleotide repeat. The unstable CTG repeat sequence is located in the 3¢ untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene on the long arm of chromosome 19. In the general population, the CTG repeat ranges from five to 37 units, whereas in DM1 it exceeds 50 units and can increase to several thousand units. Progressive expansion of CTG amplification appears unstable and is biased towards amplification. It explains both the anticipation phenomenon observed in DM1 pedigrees and the variable clinical expression among affected individuals.DM1 is classified according to clinical manifestations, severity, and age at onset.2 Four types of DM1 are distinguished:(1) a mild form with cataracts and minimal muscular or no symptoms with onset in middle or older age; (2) a typical form with neuromuscular symptomatology with onset in adolescence or early adult life; (3) a childhood form with learning disability ⁄ learning difficulties ofte...

Dystrophie myotonique de Steinert congénitale chez un grand prématuré : questionnements éthiques

“…Le déficit intellectuel est constant, avec un quotient intellectuel (QI) généralement compris entre 40 et 70. L'atteinte du langage et les perturbations fréquentes de l'attention et du comportement empêchent aussi un cursus scolaire normal [9,16,17]. Les troubles intellectuels, moteurs, musculaires et langagiers sont nettement plus marqués dans les formes congénitales qu'infantiles ou juvéniles [9].…”

Clinical, pathological and genetic characteristics of a pedigree with myotonic dystrophy type 1

“…Central nervous system involvement may commonly be exhibited as mental retardation, daytime sleepiness and night-time sleep disorders. The patients may also have personality disorders, manifested as compulsion, irritability or apathy (21). Digestive system involvement may include cholecystitis, cholelithiasis, abnormal liver functions, intestinal pseudo-obstruction and congenital megacolon, and also delayed gastric emptying, diarrhea and other symptoms.…”

Intérêt des traitements pharmacologiques symptomatiques des maladies neuromusculaires de l’enfant

“…Dans la dystrophie myotonique de Steinert, les troubles comportementaux et cognitifs sont également fréquents : phobies, troubles de l'humeur, troubles anxieux et THADA dans près d'un tiers des cas. L'intérêt du méthylphénidate chez ces patients Steinert avec THADA a également été rapporté [18,19].…”