Despite having the same underlying genetic etiology, individuals with the same syndromic form of intellectual developmental disability (IDD) show a large degree of interindividual differences in cognition and IQ. Research indicates that up to 80% of the variation in IQ scores among individuals with syndromic IDDs is attributable to nongenetic effects, including social-environmental factors. In this narrative review, we summarize evidence of the influence that factors related to economic stability (focused on due to its prevalence in existing literature) have on IQ in individuals with syndromic IDDs. We also highlight the pathways through which economic stability is hypothesized to impact cognitive development and drive individual differences in IQ among individuals with syndromic IDDs. We also identify broader social-environmental factors (e.g., social determinants of health) that warrant consideration in future research, but that have not yet been explored in syndromic IDDs. We conclude by making recommendations to address the urgent need for further research into other salient factors associated with heterogeneity in IQ. These recommendations ultimately may shape individual- and community-level interventions and may inform systems-level public policy efforts to promote the cognitive development of and improve the lived experiences of individuals with syndromic IDDs.

Children with fragile X syndrome (FXS) often avoid eye contact, a behavior that is potentially related to hyperarousal. Prior studies, however, have focused on between-person associations rather than coupling of within-person changes in gaze behaviors and arousal. In addition, there is debate about whether prompts to maintain eye contact are beneficial for individuals with FXS. In a study of young females (ages 6–16), we used eye tracking to assess gaze behavior and pupil dilation during social interactions in a group with FXS (n = 32) and a developmentally similar comparison group (n = 23). Participants engaged in semi-structured conversations with a female examiner during blocks with and without verbal prompts to maintain eye contact. We identified a social–behavioral and psychophysiological profile that is specific to females with FXS; this group exhibited lower mean levels of eye contact, significantly increased mean pupil dilation during conversations that included prompts to maintain eye contact, and showed stronger positive coupling between eye contact and pupil dilation. Our findings strengthen support for the perspective that gaze aversion in FXS reflects negative reinforcement of social avoidance behavior. We also found that behavioral skills training may improve eye contact, but maintaining eye contact appears to be physiologically taxing for females with FXS.

Prospective longitudinal studies of idiopathic autism spectrum disorder (ASD) have provided insights into early symptoms and predictors of ASD during infancy, well before ASD can be diagnosed at age 2–3 years. However, research on the emergence of ASD in disorders with a known genetic etiology, contextualized in a developmental framework, is currently lacking. Using a biobehavioral multimethod approach, we (a) determined the rate of ASD in N = 51 preschoolers with fragile X syndrome (FXS) using a clinical best estimate (CBE) procedure with differential diagnoses of comorbid psychiatric disorders and (b) investigated trajectories of ASD symptoms and physiological arousal across infancy as predictors of ASD in preschoolers with FXS. ASD was not diagnosed if intellectual ability or psychiatric disorders better accounted for the symptoms. Our results determined that 60.7% of preschoolers with FXS met the Diagnostic and Statistical Manual of Mental Disorders (fifth edition) (DSM-5) criteria for ASD using the CBE procedure. In addition, 92% of these preschoolers presented with developmental delay and 45.4% also met criteria for psychiatric disorders, either anxiety, ADHD, or both. ASD diagnoses in preschoolers with FXS were predicted by elevated scores on traditional ASD screeners in addition to elevated autonomic arousal and avoidant eye contact from infancy.

A large body of literature has accumulated within the last decade concerning the fragile X syndrome, the most common cause of X-linked mental retardation. The first article of this review summarizes the peculiar genetic mechanisms and molecular biology properties (eg, unstable DNA triplet repeats), which have been characterized since the detection of the FMR-1 gene in 1991. However, the most important question concerning the function of the FMR-1 gene is still an unresolved issue and is in need of future research. The second article of this review addresses the clinical picture, neuropsychological functioning and psychopathological characteristics of pre- and full mutation carriers.

Fragile X syndrome (FXS) – the leading cause of inherited mental retardation – is an X-linked disease caused by loss of expression of the FMR1 (fragile X mental retardation 1) gene. In addition to impairment of higher-cognitive functions, FXS patients show a variety of physical and other mental abnormalities. FMRP, the protein encoded by the FMR1 gene, is thought to play a key role in translation, trafficking and targeting of mRNA in neurons. To better understand FMRP's functions, the protein partners and mRNA targets that interact with FMRP have been sought. These and functional studies have revealed links with processes such as cytoskeleton remodelling via the RhoGTPase pathway and mRNA processing via the RNA interference pathway. In this review, we focus on recent insights into the function of FMRP and speculate on how the absence of FMRP might cause the clinical phenotypes seen in FXS patients. Finally, we explore potential therapies for FXS.

Over the past two decades, mental retardation research converges on three general themes: co-occurring mental retardation and psychopathology; families of offspring with mental retardation; and the developmental approach regarding behavioral sequences and profiles. Intertwined with each theme is a mounting body of research on genetic mental retardation syndromes. We first review recent progress in each of the three domains—psychopathology, families, and development—based on studies of groups with heterogenous or nonspecific mental retardation. We then show how new findings from specific genetic syndromes take this knowledge even further, as well as aid in the search for genetic, physiological, and environmental mechanisms associated with certain behaviors. We end the review by briefly summarizing our reasons for promoting an etiological approach to future mental retardation research, as well as by discussing methodological and other challenges.

Recent advances are reviewed in understanding the heightened prevalence of psychopathology and maladaptive behavior among children with intellectual disability. Researchers have traditionally emphasized measurement and prevalence issues, using either psychiatric assessments or rating scales to identify the prevalence of various problems in children with intellectual disability. Yet the time is ripe to shift directions, and identify more precisely why children are at increased risk for psychopathology to begin with. Although several “bio- psycho-social” hypotheses are reviewed, a particularly promising line of work links psychopathology to genetic intellectual disability syndromes. Psychiatric vulnerabilities in several syndromes are reviewed, as are the advantages of phenotypic work for understanding psychopathology among children with intellectual disability more generally.

The fragile X mutation is the result of an abnormal expansion of a CGG repeat sequence in the FMR-1 gene.

Molecular techniques enable the detection of the mutation and also of the exact length of this DNA sequence, allowing the classification of the tested subjects as normal, carrier or affected.

We propose a protocol of analysis that combines a method of non-radioactive PCR, Southern blotting and cytogenetic testing.

This protocol can be used for screening programme of selected groups of mentally retarded individuals and for prevention studies in families at risk.