Longitudinal study of cognitive abilities and adaptive behavior levels in fragile X males: A prospective multicenter analysis

Abstract

Retrospective longitudinal studies have noted declines in IQ scores in many but not all fra(X) (fragile X) males and females. We report on a prospective investigation of longitudinal changes in cognitive ability (IQ) and adaptive behavior (DQ) in 24 fra(X) males from four test sites. Individuals who were tested ranged in age from 3–15 years. To determine cognitive ability, all males were administered the Stanford‐Binet test (4th Edition). To assess adaptive behavior, all males were evaluated using the Vineland Adaptive Behavior Scales. Mean intertest interval was 2.3 years. Using identical DNA protocols, all subjects were identified as bearing the fra(X) mutation. Results showed declines in IQ scores in 18/24 (75%) males. Four males showed no change in scores. Declines in DQ scores were noted in 22/24 (92%) of those tested. DQ scores were higher than IQ scores in 20/24 (83%) subjects. From a descriptive cohort analysis, decreases in IQ scores appear to follow a well‐defined, negatively decelerating function. Declines in DQ were steeper and more nearly linear. Declining scores are not indicative of regression of intellectual and/or social skills, but of a relative inability to keep pace with their age‐normed cohort. We conclude that the fra(X) mutation affects cognitive abilities in a uniform, nonlinear manner comparable to outcomes observed in earlier retrospective studies. Adaptive behavior also declines, but in a more linear fashion. © 1996 Wiley‐Liss, Inc.

Longitudinal Changes in Intellectual Development in Children with Fragile X Syndrome

“…Specifically, during the interval between evaluations, the unaffected children gained 2.2 times as many percentage points per year, as compared with the FXS group. Given that the IQ's of the unaffected children (derived as standardized scores) presumably remained stable over the course of this study, this widening gap between the two groups accounts for the apparent drop in IQ scores in children with FXS reported by previous investigators (e.g., Fisch et al 1994Fisch et al , 1996. This apparent drop in the IQ's of children with FXS over time therefore reflects a greater slowing of intellectual development than unaffected children.…”

“…For example, in a retrospective study, IQ decreases were observed in 9 of 11 (82%) females with FXS (mean decrease of 9 standardized points; Fisch et al 1994). In a subsequent prospective study of a different group of 13 girls with FXS, significant IQ decreases were again observed in eight subjects (Fisch et al 1996). Yet, a review of these studies suggests that not all individuals with FXS show declining IQs over time (Hagerman et al 1989; Wright-Talamante et al 1996).…”

Retards mentaux liés à l’X

“…Toutefois, dans de nombreux cas familiaux dont le phénotype est clairement lié à l'X (58 sur les 80 familles RMX, par exemple), aucune mutation n'a été trouvée, soit parce que la recherche de mutations n'a pas été systématiquement effectuée pour tous les gènes RMLX connus dans un intervalle génétique donné, soit parce qu'elles affectent de nouveaux gènes non encore identifiés. Ainsi, le nombre total de gènes impliqués dans les RMLX est difficile à estimer à ce jour, et pourrait varier du simple au double (jusqu'à 100) [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] …”

“…Celui-ci est le plus souvent modéré [2,3], et l'examen neuro-anatomique de cerveaux de patients a mis en évidence des défauts morphologiques au niveau des épines dendritiques (compartiments post-synaptiques de la plupart des neurones excitateurs) [4]. Ces observations suggèrent qu'un défaut de connexion entre les neurones puisse limiter la transmission synaptique, le RM étant alors l'expression clinique de ces limitations.…”

“…Arrêt prématuré de l'ovulation et diminution de la réserve ovarienne La survenue d'une aménorrhée hypo-oestrogénique avant 40 ans, encore appelée ménopause précoce, survient chez 20 % des femmes prémutées [1,2]. Parallèlement, des études réalisées auprès d'un grand nombre de femmes souffrant d'une ménopause précoce ont montré la présence, en quantité non négligeable, de femmes porteuses d'une prémutation [3]. Des travaux récents semblent montrer qu'il existe une corrélation entre l'importance des répétitions et la réserve ovocytaire [4].…”