Browsing by Author "Hagerman, Randi J. (7006679292)"

Background: The majority of individuals with fragile X syndrome (FXS) have intellectual disability, behavioral problems, autism, and language deficits. IQ typically declines with age in boys with the full mutation. The results of preclinical studies demonstrated that metformin, a biguanide used to treat type 2 diabetes, rescues multiple phenotypes of FXS in both Drosophila and mouse models. Preliminary studies of patients with FXS demonstrated improvements in behavior. Methods: Here, we present two cases of individuals who have been treated with metformin clinically for one year. Results: Both patients demonstrated significant cognitive and behavioral improvements. They also improved eating habits and normalization of their weight percentiles. Conclusion: Metformin may be a candidate drug for treatment of several types of symptoms in individuals with FXS. © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Background: The majority of individuals with fragile X syndrome (FXS) have intellectual disability, behavioral problems, autism, and language deficits. IQ typically declines with age in boys with the full mutation. The results of preclinical studies demonstrated that metformin, a biguanide used to treat type 2 diabetes, rescues multiple phenotypes of FXS in both Drosophila and mouse models. Preliminary studies of patients with FXS demonstrated improvements in behavior. Methods: Here, we present two cases of individuals who have been treated with metformin clinically for one year. Results: Both patients demonstrated significant cognitive and behavioral improvements. They also improved eating habits and normalization of their weight percentiles. Conclusion: Metformin may be a candidate drug for treatment of several types of symptoms in individuals with FXS. © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Fragile X syndrome (FXS) is caused by the full mutation (>200 CGG repeats) in the Fragile X Mental Retardation 1 (FMR1) gene. It is the most common inherited cause of intellectual disability (ID) and autism. This review focuses on neuropsychiatric disorders frequently experienced by premutation carriers with 55 to 200 CGG repeats and the pathophysiology involves elevated FMR1 mRNA levels, which is different from the absence or deficiency of fragile X mental retardation protein (FMRP) seen in FXS. Neuropsychiatric disorders are the most common problems associated with the premutation, and they affect approximately 50% of individuals with 55 to 200 CGG repeats in the FMR1 gene. Neuropsychiatric disorders in children with the premutation include anxiety, ADHD, social deficits, or autism spectrum disorders (ASD). In adults with the premutation, anxiety and depression are the most common problems, although obsessive compulsive disorder, ADHD, and substance abuse are also common. These problems are often exacerbated by chronic fatigue, chronic pain, fibromyalgia, autoimmune disorders and sleep problems, which are also associated with the premutation. Here we review the clinical studies, neuropathology and molecular underpinnings of RNA toxicity associated with the premutation. We also propose the name Fragile X-associated Neuropsychiatric Disorders (FXAND) in an effort to promote research and the use of fragile X DNA testing to enhance recognition and treatment for these disorders. Copyright © 2018 Hagerman, Protic, Rajaratnam, Salcedo-Arellano, Aydin and Schneider.

Fragile X Syndrome (FXS) is the most common cause of inherited intellectual disability with prevalence rates estimated to be 1:5,000 in males and 1:8,000 in females. The increase of >200 Cytosine Guanine Guanine (CGG) repeats in the 5’ untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene results in transcriptional silencing on the FMR1 gene with a subsequent reduction or absence of fragile X mental retardation protein (FMRP), an RNA binding protein involved in the maturation and elimination of synapses. In addition to intellectual disability, common features of FXS are behavioral problems, autism, language deficits and atypical physical features. There are still no currently approved curative therapies for FXS, and clinical management continues to focus on symptomatic treatment of comorbid behaviors and psychiatric problems. Here we discuss several treatments that target the neurobiological pathway abnormal in FXS. These medications are clinically available at present and the data suggest that these medications can be helpful for those with FXS. © 2019 Bentham Science Publishers.

Fragile X–associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that usually begins in the early 60s and affects carriers of premutation expansion (55–200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. Additional disorders can co-occur with FXTAS including Alzheimer’s disease (AD). Here we discuss a case report of a male with 67 CGG repeats in FMR1 who had mild late-onset FXTAS symptoms followed by neurocognitive disorder symptoms consistent with AD. The patient has developed tremor and ataxia that are the two characteristic symptoms of FXTAS. In addition, he shows rapid cognitive decline, brain atrophy most substantial in the medial temporal lobe, and decreased metabolism in the brain regions that are the characteristic findings of AD. The purpose of this study is to describe a patient profile with both diseases and review the details of an overlap between these two diseases. © 2020 Aydin et al.