The Trajectory of Cognitive Development in Males with Fragile X Syndrome

Dykens, Elisabeth M.; Hodapp, Robert M.; Ort, Sharon I.; Finucane, Brenda; Shapiro, Laurence R.; Leckman, James F.

doi:10.1097/00004583-198905000-00020

Cited by 105 publications

(79 citation statements)

References 20 publications

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“…These findings confirm results previously obtained by other investigators. However, the relationship between age and I& appears to be nonlinear and I& similar to one noted by Dykens et al [1989].…”

Section: Resultssupporting

confidence: 61%

Relationship between age and IQ among fragile X males: A multicenter study

Fisch

Arinami²,

Froster-Iskenius

et al. 1991

Am. J. Med. Genet.

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Longitudinal decline in IQ among fragile X males was reported recently. However, there are problems in retesting IQ that may affect scores. Two such factors are intertest time interval and score obtained on the first test. To determine the generality of IQ score changes, we examined 101 fragile X males from 6 centers. To ensure high test-retest reliability, only results from Stanford-Binet and Wechsler tests were used. Thus there were retest scores from 60 subjects. Test-retest reliability between first and last scores was very good (r = 0.85) and comparable to those seen in nonfragile X mentally retarded individuals. Also computed were z-scores of differences in IQ scores. The z-score differences were distributed about a mean at 1 SD below the expected zero value. Eighteen subjects showed statistically significant decreases in IQ, 6 showed statistically significant increases, while 5 showed the same scores. Z-score differences were not correlated with type of residence or elapsed intertest interval, but were negatively correlated with first score obtained, indicating a regression-to-the-mean effect. Using a multiple regression analysis, we found first score obtained, age tested, and age retested significant predictors of score differences, accounting for 19% of the total variance. These results suggest that factors previously identified as affecting retest scores have a smaller effect than originally thought. It is suspected that decline in IQ is associated with dynamic neurological processes and needs to be investigated further.

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Section: Resultssupporting

confidence: 61%

Relationship between age and IQ among fragile X males: A multicenter study

Fisch

Arinami²,

Froster-Iskenius

et al. 1991

Am. J. Med. Genet.

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“…These include fragile X syndrome, in which lossof-function in FMR1 12 leads to intellectual disability. 13 The most common mechanism leading to fragile X syndrome is a CGG trinucleotide repeat expansion in the promoter region of the FMR1 gene leading to methylation of the promoter of the gene, with subsequent silencing of transcription and the absence of the encoded product FMRP, 14 which is important for synaptic plasticity and synaptic protein synthesis. 15,16 However, other loss-of-function mutations, including deletions, missense mutations and splice-site mutations, have been reported.…”

Section: Discussionmentioning

confidence: 99%

De novo microduplication of the FMR1 gene in a patient with developmental delay, epilepsy and hyperactivity

et al. 2012

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Loss-of-function due to expansion of a CGG repeat located in the 5'UTR of the FMR1 gene is the most frequent cause of fragile X syndrome. Less than 1% of individuals with fragile X syndrome have been reported to have a partial or full deletion or point mutation of the FMR1 gene. However, whether a copy number gain of the FMR1 gene could result in certain clinical phenotypes has not been fully investigated. Here, we report the case of a child who presented with developmental delay starting at 9 months of age, fine motor and speech delay, progressive seizures since 18 months of age and hyperactivity. Molecular workup identified a de novo microduplication in the Xq27.3 region, including the FMR1 gene and the ASFMR1 gene. The expression level of the FMR1 gene in peripheral blood did not differ from that of the controls. In addition, an inherited 363-kb duplication on the chromosome 1q44 region and an inherited deletion of 168 kb on the chromosome 4p15.31 region were detected. It is not clear whether these inherited copy number variations (CNVs) also have a modifying role in the clinical phenotype of this patient.

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“…Dykens et al [1989] examined the relationship between age and cognitive-behavioral features in older children and young adolescents with the FRAXA mutation. They reported that, although age-equivalent cognitive ability was directly related to increasing chronological age, increases gradually slowed, forming a ''plateau.''…”

Section: Discussionmentioning

confidence: 99%

Studies of age‐correlated features of cognitive‐behavioral development in children and adolescents with genetic disorders

Fisch

Carpenter²,

Howard‐Peebles

et al. 2007

American J of Med Genetics Pt A

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Studies of age-related features of cognitive-behavioral deficits produced by genetic mutations permit us to draw inferences about how brain development may be related cognitive ability as the child ages. Except for Down syndrome (DS) and the fragile X mutation (FRAXA), little is known about the longitudinal changes in cognitive-behavioral development in individuals with genetic abnormalities producing learning disabilities (LD) or mental retardation (MR). The purpose of this prospective study was to compare and contrast age related to cognitive abilities, adaptive and maladaptive behaviors in children and adolescents in the same age range, diagnosed with one of three genetic disorders: the FRAXA mutation, Neurofibromatosis type 1 (NF1) or Williams-Beuren syndrome (WBS). We also sought to examine whether cognitive-behavioral abilities associated with these three genetic disorders were related systematically to age. We examined 108 children, ages 4-15 years, with FRAXA, WBS, or NF1. Results show that there is a significant negative correlation between age and IQ, and between age and adaptive behavior (DQ) scores, in children with FRAXA and WBS, but not in children with NF1. All three groups of children have unusually high proportions of maladaptive behavior, ranging from 1/6 children with NF1 to 2/3 children with FRAXA. Cognitive and adaptive behavior profiles of children with FRAXA and WBS were also surprisingly similar. Our findings suggest the need for examining longitudinal developmental cognitive-behavioral changes in children and adolescents with all genetic disorders that produce LD or MR.

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The Trajectory of Cognitive Development in Males with Fragile X Syndrome

Cited by 105 publications

References 20 publications

Relationship between age and IQ among fragile X males: A multicenter study

Relationship between age and IQ among fragile X males: A multicenter study

De novo microduplication of the FMR1 gene in a patient with developmental delay, epilepsy and hyperactivity

Studies of age‐correlated features of cognitive‐behavioral development in children and adolescents with genetic disorders

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