Movement disorders in Rett syndrome: an analysis of 60 patients with detected MECP2 mutation and correlation with mutation type.
Rett syndrome (RS) is one of the best human models to study movement disorders. Patients evolve from a hyperkinetic to a hypokinetic state, and a large series of abnormal movements may be observed along their lives such as stereotypies, tremor, chorea, myoclonus, ataxia, dystonia, and rigidity. The aim of this work was to analyze movement disorders in RS patients with a detected MECP2 mutation, as well as their correlation with genotype, in a clinically and genetically well-characterized sample of patients, and thus contribute to redefine the clinical profile of this disease. In this study, we included 60 patients with detected MECP2 mutations. These were categorized and grouped for analysis, according to (1) type of change (missense or truncating, including nonsense and frameshift but also large deletions) and (2) location of the mutation. Differences were found concerning the frequency of independent gait, dystonia, type of tremor, and global score severity when comparing the group of patients with missense and truncating mutations. We also found differences in the presence, distribution, severity, or type of movement disorders in the two groups of patients according to the median duration of the disease (less than 60 months; 60 months or more). We conclude that movement disorders seem to reflect the severity and rate of progression of Rett disorder, patients with truncating mutations presenting a higher rate and more severe dystonia and rigid-akinetic syndrome, when comparing groups with similar time of disease evolution.
Temudo
Teresa
T
Unidade de Neuropediatria, Serviço de Pediatria, Hospital Geral de Santo António, Porto, Portugal. teresatemudo@netcabo.pt
Ramos
Elisabete
E
Dias
Karin
K
Barbot
Clara
C
Vieira
Jose P
JP
Moreira
Ana
A
Calado
Eulalia
E
Carrilho
Ines
I
Oliveira
Guiomar
G
Levy
Antonio
A
Fonseca
Maria
M
Cabral
Alexandra
A
Cabral
Pedro
P
Monteiro
Joao P
JP
Borges
Luis
L
Gomes
Roseli
R
Santos
Manuela
M
Sequeiros
Jorge
J
Maciel
Patricia
P
D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D018450:Disease Progression; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000502:physiology; D009069:Movement Disorders / Q000209:etiology*; D009154:Mutation; D020125:Mutation, Missense; D015518:Rett Syndrome / Q000150:complications* / Q000235:genetics; D017384:Sequence Deletion; D012720:Severity of Illness Index; D019956:Stereotypic Movement Disorder / Q000209:etiology; D013997:Time Factors
D018389:Codon, Nonsense; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2