Anxiety disorders in fragile X premutation carriers: Preliminary characterization of probands and non-probands

Cordeiro, Lisa; Abucayan, Floridette; Hagerman, Randi J.; Tassone, Flora; Hessl, David

doi:10.5582/irdr.2015.01029

Cited by 48 publications

(52 citation statements)

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“…FMR1 premutation is known to cause neurodegeneration with aging in a subgroup of carriers, most commonly males beginning in their 60s (Hagerman and Hagerman, 2013; Berry-Kravis et al, 2007). However, developmental problems can also occur in those with the premutation, the most common including ADHD, ASD and social anxiety (Chonchaiya et al, 2012; Farzin et al, 2006; Cordeiro et al, 2015). …”

Section: Discussionmentioning

confidence: 99%

“…Case 3 did not have exposure to phenobarbital but she had developmental problems including mutism associated with developmental delay. Her mutism may be related to the anxiety problems seen in premutation carriers (Cordeiro et al, 2015), and it is usually responsive to a selective serotonin reuptake inhibitor such as sertraline as well as speech and language therapy when treatment is started early.…”

Section: Discussionmentioning

confidence: 99%

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Phenobarbital use and neurological problems in FMR1 premutation carriers

et al. 2016

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Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by a CGG expansion in the FMR1 gene located at Xq27.3. Patients with the premutation in FMR1 present specific clinical problems associated with the number of CGG repeats (55–200 CGG repeats). Premutation carriers have elevated FMR1 mRNA expression levels, which have been associated with neurotoxicity potentially causing neurodevelopmental problems or neurological problems associated with aging. However, cognitive impairments or neurological problems may also be related to increased vulnerability of premutation carriers to neurotoxicants, including phenobarbital. Here we present a study of three sisters with the premutation who were exposed differentially to phenobarbital therapy throughout their lives, allowing us to compare the neurological effects of this drug in these patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Phenobarbital use and neurological problems in FMR1 premutation carriers

et al. 2016

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“…Mild social deficits are common among carriers 16 and usually present as social anxiety and/or social phobia 12,17 . Approximately 10% of boys with the premutation meet the diagnostic criteria for ASD, which is usually recognized in childhood 14,18,19 .…”

Section: Features Of Premutation Disordersmentioning

confidence: 99%

“…Behavioural features associated with the premutation alleles include anxiety 9-12 , obsessive-compulsive traits [12][13][14] and depression 9,10,15 . Mild social deficits are common among carriers 16 and usually present as social anxiety and/or social phobia 12,17 .…”

Section: Features Of Premutation Disordersmentioning

confidence: 99%

Fragile X-associated tremor/ataxia syndrome — features, mechanisms and management

2016

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Many physicians are unaware of the many phenotypes associated with the fragile X premutation, an expansion in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene that consists of 55-200 CGG repeats. The most severe of these phenotypes is fragile X-associated tremor/ataxia syndrome (FXTAS), which occurs in the majority of ageing male premutation carriers but in fewer than 20% of ageing women with the premutation. The prevalence of the premutation is 1 in 150-300 females, and 1 in 400-850 males, so physicians are likely to see people affected by FXTAS. Fragile X DNA testing is broadly available in the Western world. The clinical phenotype of FXTAS at presentation can vary and includes intention tremor, cerebellar ataxia, neuropathic pain, memory and/or executive function deficits, parkinsonian features, and psychological disorders, such as depression, anxiety and/or apathy. FXTAS causes brain atrophy and white matter disease, usually in the middle cerebellar peduncles, the periventricular area, and the splenium and/or genu of the corpus callosum. Here, we review the complexities involved in the clinical management of FXTAS and consider how targeted treatment for these clinical features of FXTAS will result from advances in our understanding of the molecular mechanisms that underlie this neurodegenerative disorder. Such targeted approaches should also be more broadly applicable to earlier forms of clinical involvement among premutation carriers.

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“…Anxiety disorders are seen in a high proportion of individuals with FXS, and recent evidence shows that PM carriers are also at risk for anxiety disorders with a higher rate of anxiety disorder than expected in the general population (Bourgeois et al, 2007; Bourgeois et al, 2011; Cordeiro, Abucayan, Hagerman, Tassone, & Hessl, 2015). The development of anxiety-related behaviors has also been reported in CGG KI mice that show an age-dependent increase in anxiety in the open-field locomotor test.…”

Section: How Is Fxtas Modeled In Mice?mentioning

confidence: 99%

What has been learned from mouse models of the Fragile X Premutation and Fragile X-associated tremor/ataxia syndrome?

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Careaga

Berman

2016

The Clinical Neuropsychologist

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Objective To describe in this review how research using mouse models developed to study the Fragile X premutation (PM) and Fragile X-associated tremor/ataxia syndrome (FXTAS) have contributed to understanding these disorders. PM carriers bear an expanded CGG trinucleotide repeat on the Fragile X Mental Retardation 1 (FMR1) gene, and are at risk for developing the late-onset neurodegenerative disorder FXTAS. Conclusions Much has been learned about these genetic disorders from the development and study of mouse models. This includes new insights into the early cellular and molecular events that occur in PM carriers and in FXTAS, the presence of multi-organ pathology beyond the CNS, immunological dysregulation, unexpected synthesis of a potentially toxic peptide in FXTAS (i.e., FMRpolyG), and evidence that the disease process may be halted or reversed by appropriate molecular therapies given early in the course of disease.

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Anxiety disorders in fragile X premutation carriers: Preliminary characterization of probands and non-probands

Cited by 48 publications

References 59 publications

Phenobarbital use and neurological problems in FMR1 premutation carriers

Phenobarbital use and neurological problems in FMR1 premutation carriers

Fragile X-associated tremor/ataxia syndrome — features, mechanisms and management

What has been learned from mouse models of the Fragile X Premutation and Fragile X-associated tremor/ataxia syndrome?

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