Article

Motor abilities of children diagnosed with fragile X syndrome with and without autism

Occupational Therapy Department, Rady Children Hospital, San Diego, CA, USA.
Journal of Intellectual Disability Research (Impact Factor: 2.41). 10/2008; 53(1):11-8. DOI: 10.1111/j.1365-2788.2008.01107.x
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ABSTRACT Previous studies suggested that children diagnosed with fragile X syndrome (FXS) often meet criteria for autism or PDD. This study describes the fine motor abilities of children diagnosed with FXS with and without autism spectrum disorder, and compares the motor scores of those groups controlling for cognitive level.
Forty-eight children, ages 12-76 months (SD = 16) diagnosed with FXS were assessed with the Mullen Scales of Early Learning, and the Autism Diagnostic Observation Schedule. Their parents were interviewed with the Autism Diagnostic Interview-Revised. We used a one-way analysis of variance to determine if the fine motor scale of the Mullen would show group differences based on autism classifications for the sample. In addition, we used Pearson correlation coefficient to examine the relationship between the cognitive level, the autism severity and the motor abilities. Lastly, we conducted a one-way analysis of covariance to determine the difference between the motor abilities of the Autism Spectrum Disorder groups controlling for cognitive level.
We found that 60% of the children with FXS met criteria for autism or Pervasive Developmental Disorder - Not otherwise specified (PDD-NOS). Children with FXS with autism and PDD-NOS had lower fine motor scores than those without. However, there was no significant association between degree of motor impairment and communication and social impairments after controlling for cognitive level, indicating that cognitive level contributes to impaired motor abilities of children diagnosed with FXS and autism, more than the severity of autism symptoms.
children with FXS and autism are at risk for impaired motor abilities. Implications for development and intervention are discussed.

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Available from: Chaya Zingerevich, Jul 10, 2014
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    • "The monogenic FXS disease state (Verkerk et al., 1991) is typically caused by an unstable 5 trinucleotide expansion in the promoter region of the Fmr1 gene leading to hypermethylation and transcriptional silencing (Leehey et al., 2008). FXS patients exhibit delayed developmental trajectories, working memory deficits, circadian defects, hypersensitivity to sensory input, seizures, increased anxiety and hyperactivity (Harris et al., 2008), and a 30% comorbidity with autism (Zingerevich et al., 2009). Furthermore, FMRP may be associated with other neurological disease states, as schizophrenic patients have reduced FMRP in the periphery (Kovacs et al., 2013) and cerebellum (Fatemi et al., 2010), correlating with poor performance on perceptual integration tasks (Kelemen et al., 2013). "
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    ABSTRACT: Early-use activity during circuit-specific critical periods refines brain circuitry by the coupled processes of eliminating inappropriate synapses and strengthening maintained synapses. We theorize these activity-dependent (A-D) developmental processes are specifically impaired in autism spectrum disorders (ASDs). ASD genetic models in both mouse and Drosophila have pioneered our insights into normal A-D neural circuit assembly and consolidation, and how these developmental mechanisms go awry in specific genetic conditions. The monogenic fragile X syndrome (FXS), a common cause of heritable ASD and intellectual disability, has been particularly well linked to defects in A-D critical period processes. The fragile X mental retardation protein (FMRP) is positively activity-regulated in expression and function, in turn regulates excitability and activity in a negative feedback loop, and appears to be required for the A-D remodeling of synaptic connectivity during early-use critical periods. The Drosophila FXS model has been shown to functionally conserve the roles of human FMRP in synaptogenesis, and has been centrally important in generating our current mechanistic understanding of the FXS disease state. Recent advances in Drosophila optogenetics, transgenic calcium reporters, highly-targeted transgenic drivers for individually-identified neurons, and a vastly improved connectome of the brain are now being combined to provide unparalleled opportunities to both manipulate and monitor A-D processes during critical period brain development in defined neural circuits. The field is now poised to exploit this new Drosophila transgenic toolbox for the systematic dissection of A-D mechanisms in normal versus ASD brain development, particularly utilizing the well-established Drosophila FXS disease model.
    Frontiers in Cellular Neuroscience 02/2014; 8:30. DOI:10.3389/fncel.2014.00030 · 4.18 Impact Factor
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    • "The cerebellum is well known to play a crucial role in speech articulation (Spencer & Slocomb, 2007). Cerebellar neuropathologies are consistently found in FXS patients (Mostofsky et al., 1998; Zingerevich et al., 2009), which may partially contribute to speech articulation deficit in FXS patients. The ormotor deficit in Fmr1-KO mice described here and the speech articulation deficits in FXS patients might have common neuronal causes associated with cerebellar dysfunction. "
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    ABSTRACT: Fragile X syndrome (FXS; MIM #300624), a well-recognized form of inherited human mental retardation is caused, in most cases, by a CGG trinucleotide repeat expansion in the 5'-untranslated region of FMR1, resulting in reduced expression of the fragile X mental retardation protein (FMRP). Clinical features include macroorchidism, anxiety, mental retardation, motor coordination, and speech articulation deficits. The Fmr1 knockout (Fmr1-KO) mouse, a mouse model for FXS, has been shown to replicate the macroorchidism, cognitive deficits, and neuroanatomical abnormalities found in human FXS. Here we asked whether Fmr1-KO mice also display appendicular and oromotor deficits comparable to the ataxia and dysarthric speech seen in FXS patients. We employed standard motor tests for balance and appendicular motor coordination, and used a novel long-term fluid-licking assay to investigate oromotor function in Fmr1-KO mice and their wild-type (WT) littermates. Fmr1-KO mice performed equally well as their WT littermates on standard motor tests, with the exception of a raised-beam task. However, Fmr1-KO mice had a significantly slower licking rhythm than their WT littermates. Deficits in rhythmic fluid-licking in Fmr1-KO mice have been linked to cerebellar pathologies. It is believed that balance and motor coordination deficits in FXS patients are caused by cerebellar neurophathologies. The neuronal bases of speech articulation deficits in FXS patients are currently unknown. It is yet to be established whether similar neuronal circuits control rhythmic fluid-licking pattern in mice and speech articulation movement in humans.
    Behavioral Neuroscience 12/2011; 125(6):962-9. DOI:10.1037/a0025920 · 3.25 Impact Factor
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    • "The most well documented phenotypic feature in FXS is its high association with autism in terms of increased core and associated features as well as diagnostic classification with 25–50% of males with FXS meeting DSM IV criteria for autism (Hall et al. 2008; Harris et al. 2008). Young children with FXS exhibit elevated rates of autism with 25–27% of 1–8 year-olds meeting criteria for autism using DSM IV based measures (Zingerevich et al. 2009). These studies unambiguously demonstrate that there is a high association with autism in young children with FXS. "
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    ABSTRACT: Aberrant attention is a core feature of fragile X syndrome (FXS), however, little is known regarding the developmental trajectory and underlying physiological processes of attention deficits in FXS. Atypical visual attention is an early emerging and robust indictor of autism in idiopathic (non-FXS) autism. Using a biobehavioral approach with gaze direction and heart activity, we examined visual attention in infants with FXS at 9, 12, and 18 months of age with a cross-sectional comparison to 12-month-old typically developing infants. Analyses revealed lower HR variability, shallower HR decelerations, and prolonged look durations in 12-month old infants with FXS compared to typical controls. Look duration and increased latency to disengage attention were correlated with severity of autistic behavior but not mental age.
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