RESUMO
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.
Assuntos
Síndrome do Cromossomo X Frágil/tratamento farmacológico , Agonistas GABAérgicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Terapia de Alvo Molecular , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , Reprogramação Celular/genética , Criança , Metilação de DNA , Modelos Animais de Doenças , Epigênese Genética , Proteína do X Frágil da Deficiência Intelectual , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/fisiopatologia , Humanos , Terapia de Alvo Molecular/tendências , Transdução de Sinais , Resultado do TratamentoRESUMO
Mutations in the Fragile X Mental Retardation 1 (FMR1) gene create a spectrum of developmental disorders in children in addition to neurodegenerative problems in older populations. Two types of mutations are recognized in the FMR1 gene. The full mutation (>200 CGG repeats) in the FMR1 gene leads to Fragile X Syndrome which is the most common inherited cause of intellectual disability and autism, while the premutation (55 to 200 CGG repeats) identified among carriers leads to a range of problems linked to elevated levels of the FMR1 mRNA leading to mRNA toxicity and occasionally mildly deficient FMRP levels. Two disorders among premutation carriers have been recognized namely: the Fragile X-associated Primary Ovarian Insufficiency (FXPOI) and Fragile X-associated Tremor/Ataxia Syndrome (FXTAS). Recently, in order to recognize a group of associated disorders commonly found in premutation carriers and extensively reported in co-morbidities studies, a new distinctive name was proposed: Fragile X-associated Neuropsychiatric Disorders (FXAND). This paper will present a case report of a female premutation carrier who has encountered predominantly psychiatric problems, but also chronic pain and sleep disturbances consistent with FXAND.
