Advances in research on the fragile X syndrome

Abstract

Fragile X syndrome is a neurodevelopmental disorder that results from a single gene mutation on the X chromosome. The purpose of this review is to summarize key advances made in understanding the fragile X premutation gene seen in carriers and the full mutation gene seen in persons with the syndrome. DNA testing has replaced cytogenetic testing as the primary method for identification of fragile X, although the efficacy of protein level screening is being explored. The premutation is associated with no effects, although there is evidence of physical effects—primarily premature menopause and mild outward features of the fragile X syndrome–among premutation carriers. There is much controversy regarding premutation effects on psychological development. The few experimental studies carried out to date do not suggest noticeable or significant effects. One challenge in addressing this controversy is the sometimes ambiguous differentiation between premutation and full mutation genes. There is a well‐established yet highly variable phenotype of the full mutation. Research from this decade has helped to address specific aspects of this phenotype, including the early course of its development in males, the influence of home and family environments, the nature of social difficulties and autistic features seen in boys and girls with fragile X, and the potential role of hyperarousal or hyper‐reactivity. Studies in these areas, and on the role of FMR protein, will contribute towards ongoing advances in our understanding of fragile X syndrome and its mechanisms. The variability in physical, social, and cognitive features, as described in this review, is one that prohibits clear‐cut screening guidelines designed to avoid high rates of both false positives and false negatives. Results from recent studies indicate the need to consider behavioral features in selecting candidates for fragile X screening. MRDD Research Reviews 2000;6:96‐106. © 2000 Wiley‐Liss, Inc.

Polysomnographic Findings in Fragile X Syndrome Children with EEG Abnormalities

“…Our study contributes to the currently sparse literature characterizing sleep disturbance in FXS: in particular, it has been previously reported that children suffering from FXS show abnormal sleep patterns [54] and abnormal polysomnographic phenotypes [55] with alteration in sleep microstructure [40]. Moreover, it is important to underline that unlike most of the previous studies, the diagnosis of autism was considered as an exclusion criterion, thus eliminating this possible confounding factor [56, 57].…”

Polysomnographic Findings in Fragile X Syndrome Children with EEG Abnormalities

“…Our study contributes to the currently sparse literature characterizing sleep disturbance in FXS: in particular, it has been previously reported that children suffering from FXS show abnormal sleep patterns [54] and abnormal polysomnographic phenotypes [55] with alteration in sleep microstructure [40]. Moreover, it is important to underline that unlike most of the previous studies, the diagnosis of autism was considered as an exclusion criterion, thus eliminating this possible confounding factor [56, 57].…”

Sleep Structure in Children With Attention-Deficit/Hyperactivity Disorder

“…Lower cyclic alternating pattern rate during stage 2 NREM was also reported in Fragile X patients previously. 26 Cyclic alternating pattern alterations observed in children with ADHD might link to a deficit of executive functions as it is the case for patients with Fragile X syndrome. Although the incidence of sleep disordered breathing, which was defined as apnea-hypopnea index > 1, showed no significant difference between the groups, SpO2 in total sleep was decreased mostly because of NREM SpO2 in children with ADHD.…”

“…Lower cyclic alternating pattern rate during stage 2 NREM was also reported in Fragile X patients previously. 26 Cyclic alternating pattern alterations observed in children with ADHD might link to a deficit of executive functions as it is the case for patients with Fragile X syndrome.…”

The serotonin 1A receptor gene as a genetic and prenatal maternal environmental factor in anxiety

“…Studies in attention-deficit hyperactivity disorder suggest that the disease has a negative impact on parenting behaviors and that there are improvements in children's behavior when mothers are treated (34,35). Also, mothers with fragile X syndrome have a greater predisposition to anxiety and depression, and this predisposition may affect the postnatal environment of their children (36,37). The model of dual transmission of risk factors described here indicates that the overall effects of risk alleles can 78; P = 0.060, trend only; Distance: F 3,26 = 3.72; P = 0.023; *, P < 0.05) (n = 6-9) and have reduced immobility in the FST (ANOVA: F 3,46 = 24.56; P < 0.000001; ***, P < 0.0005; n = 11-14).…”

Polysomnographic Findings in Fragile X Syndrome Children with EEG Abnormalities

“…Our study contributes to the currently sparse literature characterizing sleep disturbance in FXS: in particular, it has been previously reported that children suffering from FXS show abnormal sleep patterns [54] and abnormal polysomnographic phenotypes [55] with alteration in sleep microstructure [40]. Moreover, it is important to underline that unlike most of the previous studies, the diagnosis of autism was considered as an exclusion criterion, thus eliminating this possible confounding factor [56, 57].…”

Sleep Structure in Children With Attention-Deficit/Hyperactivity Disorder

“…Lower cyclic alternating pattern rate during stage 2 NREM was also reported in Fragile X patients previously. 26 Cyclic alternating pattern alterations observed in children with ADHD might link to a deficit of executive functions as it is the case for patients with Fragile X syndrome. Although the incidence of sleep disordered breathing, which was defined as apnea-hypopnea index > 1, showed no significant difference between the groups, SpO2 in total sleep was decreased mostly because of NREM SpO2 in children with ADHD.…”

“…Lower cyclic alternating pattern rate during stage 2 NREM was also reported in Fragile X patients previously. 26 Cyclic alternating pattern alterations observed in children with ADHD might link to a deficit of executive functions as it is the case for patients with Fragile X syndrome.…”

The serotonin 1A receptor gene as a genetic and prenatal maternal environmental factor in anxiety

“…Studies in attention-deficit hyperactivity disorder suggest that the disease has a negative impact on parenting behaviors and that there are improvements in children's behavior when mothers are treated (34,35). Also, mothers with fragile X syndrome have a greater predisposition to anxiety and depression, and this predisposition may affect the postnatal environment of their children (36,37). The model of dual transmission of risk factors described here indicates that the overall effects of risk alleles can 78; P = 0.060, trend only; Distance: F 3,26 = 3.72; P = 0.023; *, P < 0.05) (n = 6-9) and have reduced immobility in the FST (ANOVA: F 3,46 = 24.56; P < 0.000001; ***, P < 0.0005; n = 11-14).…”

Polysomnographic Findings in Fragile X Syndrome Children with EEG Abnormalities

“…Our study contributes to the currently sparse literature characterizing sleep disturbance in FXS: in particular, it has been previously reported that children suffering from FXS show abnormal sleep patterns [54] and abnormal polysomnographic phenotypes [55] with alteration in sleep microstructure [40]. Moreover, it is important to underline that unlike most of the previous studies, the diagnosis of autism was considered as an exclusion criterion, thus eliminating this possible confounding factor [56, 57].…”

Sleep Structure in Children With Attention-Deficit/Hyperactivity Disorder

“…Lower cyclic alternating pattern rate during stage 2 NREM was also reported in Fragile X patients previously. 26 Cyclic alternating pattern alterations observed in children with ADHD might link to a deficit of executive functions as it is the case for patients with Fragile X syndrome. Although the incidence of sleep disordered breathing, which was defined as apnea-hypopnea index > 1, showed no significant difference between the groups, SpO2 in total sleep was decreased mostly because of NREM SpO2 in children with ADHD.…”

“…Lower cyclic alternating pattern rate during stage 2 NREM was also reported in Fragile X patients previously. 26 Cyclic alternating pattern alterations observed in children with ADHD might link to a deficit of executive functions as it is the case for patients with Fragile X syndrome.…”

The serotonin 1A receptor gene as a genetic and prenatal maternal environmental factor in anxiety

“…Studies in attention-deficit hyperactivity disorder suggest that the disease has a negative impact on parenting behaviors and that there are improvements in children's behavior when mothers are treated (34,35). Also, mothers with fragile X syndrome have a greater predisposition to anxiety and depression, and this predisposition may affect the postnatal environment of their children (36,37). The model of dual transmission of risk factors described here indicates that the overall effects of risk alleles can 78; P = 0.060, trend only; Distance: F 3,26 = 3.72; P = 0.023; *, P < 0.05) (n = 6-9) and have reduced immobility in the FST (ANOVA: F 3,46 = 24.56; P < 0.000001; ***, P < 0.0005; n = 11-14).…”