Functional outcomes in Rett syndrome

Abstract

Aim To relate functional outcomes to mutation type and age at evaluation in patients with Rett syndrome (RTT). Method We identified 96 RTT patients with mutations in the MECP2 (methyl-CpG-binding protein 2) gene. Chart analysis, clinical evaluation, and functional measures were completed. Results Among 11 mutation groups, a statistically significant group effect of mutation type was observed for self-care, upper extremity function, and mobility, on standardized measures administered by Occupational and Physical Therapists. Patients with R133C and uncommon mutations tended to perform best on upper extremity and self-care items, whereas patients with R133C, R306C and R294X had the highest scores on the mobility items. The worst performers on upper extremity and self-care items were patients with large deletions, R255X, R168X, and T158M mutations. The lowest scores for mobility were found in patients with T158M, R255X, R168X, and R270X mutations. On categorical variables as reported by parents at the time of initial evaluation, patients with R133C and R294X were most likely to have hand use, those with R133C, R294X, R306C and small deletions were most likely to be ambulatory, and those with R133C were most likely to be verbal. Interpretation Functional performance in RTT patients may relate to the type of mutation. Knowledge of these relationships is useful for developing appropriate rehabilitation strategies and prognosis.

Diagnostic value of partial exome sequencing in developmental disorders

“…This mutation is the second most common mutation located within the methylated-CpG-binding domain of the MECP2 protein and is causative in 4% of all patients with MECP2-related disorders [ 10 ]. In line with previous reports, patient #15 could speak single words, did not show any regression and did not develop microcephaly [ 11 ]. She met neither main nor supportive criteria for classical or even atypical Rett syndrome.…”

RettBASE: Rett syndrome database update

“…For instance, the relatively common p.Arg133Cys mutation has been shown to be of least severity compared with other common MECP2 mutations. The nonsense mutations p.Arg168 * and p.Arg255 * seen in young children are observed to be among the most clinically severe (Neul et al., ; Pidcock et al., ). Early truncating and large deletion mutations in MECP2 gene have been implicated in delayed early development and inability to walk.…”

Síndrome de Rett: revisión de la literatura con primeros casos reportados en Colombia con caracterización clínica y molecular

“…La etiología de RTT se ha establecido por alteraciones en el gen MECP2 localizado en la región Xq28p, cuya estruc-tura está compuesta por cuatro exones como se evidencia en la figura 1 y codifica una proteína de unión a metil CpG 2 (55). Una región de 80 aminoácidos llamada dominio de unión a metil CpG (MBD) cerca del N-terminal pareciera ser suficiente para enlazar el ADN metilado in vitro e in vivo.…”

“…con RTT en RettBASE (R106W, R133C, T158M, R168X, R255X, R270X, R294X, y R306C) (52,55). De todas maneras, se estima que el MECP2 está mutado en el 80-90 % de las pacientes con RTT clásico así como en el 40 % con RTT atípico, por lo que el diagnóstico debe ser esencialmente clínico ante la existencia de otros genes probablemente asociados, relacionándose por ejemplo, las variantes convulsiva temprana y congénita con mutaciones en los genes CDKL5 y FOXG1, respectivamente (5,37,59).…”

“…No obstante y pese a la evidencia existente, todavía no se ha logrado establecer una adecuada correlación entre genotipo y fenotipo, por lo que los reportes establecen que pacientes con la misma mutación pueden presentar cuadros clínicos muy diferentes. Una explicación que se ha dado al respecto, aparte del efecto de varios genes asociados, son los perfiles de inactivación selectiva del cromosoma X que varían entre una paciente y otra, incluso dentro de una misma familia (5,55,56,61). Esto permitiría un mecanismo de transmisión por madres asintomáticas rara vez documentado, aunque el 99 % de los casos son esporádicos (52,61,62).…”