Síndrome de X Frágil

Abstract

Fragile X Syndrome (FXS) is a genetic disease due to a CGG trinucleotide expansion, named full mutation (greater than 200 CGG repeats), in the fragile X mental retardation 1 gene locus Xq27.3; which leads to an hypermethylated region in the gene promoter therefore silencing it and lowering the expression levels of the fragile X mental retardation 1, a protein involved in synaptic plasticity and maturation. Individuals with FXS present with intellectual disability, autism, hyperactivity, long face, large or prominent ears and macroorchidism at puberty and thereafter. Most of the young children with FXS will present with language delay, sensory hyper arousal and anxiety. Girls are less affected than boys, only 25% have intellectual disability. Given the genomic features of the syndrome, there are patients with a number of triplet repeats between 55 and 200, known as premutation carriers. Most carriers have a normal IQ but some have developmental problems. The diagnosis of FXS has evolved from karyotype with special culture medium, to molecular techniques that are more sensitive and specific including PCR and Southern Blot. During the last decade, the advances in the knowledge of FXS, has led to the development of investigations on pharmaceutical management or targeted treatments for FXS. Minocycline and sertraline have shown efficacy in children.

Down Syndrome and Fragile X Syndrome in a Colombian Woman: Case Report

“…Knowing the literary work and the high prevalence of intellectual disability in the community, researchers from the Universidad del Valle began studies during the early 1990s performing karyotype with folate deficiency to patients with cognitive deficit, finding a total of 36 patients with evidence of fragile site on the X chromosome (diagnostic test for the disease, before the discovery of the FMR1 gene). It was determined then that the prevalence of FXS was 1 : 40 in men and 1 : 100 in women in this community (Payan et al 2001;Saldarriaga 2014). As this prevalence appeared to be far greater than the prevalence found in the global literature, fragile X DNA studies in patients and their families were carried out.…”

“…The simultaneous presence of DS and FXS in a patient has been previously reported in the literature (Anderson et al 2013;Arinami 1987;Collacott 1990;Stevens et al 2010); here, the present authors report the fifth case, the third female and the first from Colombia. The patient comes from a region with high prevalence of FXS, located in the department of Valle del Cauca in Colombia (Payan et al 2001;Saldarriaga 2014), where the present authors are currently conducting extensive investigations.…”

The Molecular Genetics of Autosomal Recessive Nonsyndromic Intellectual Disability: a Mutational Continuum and Future Recommendations

“…FMR1 encodes an RNA binding protein, f ragile X m ental r etardation p rotein (FMRP), that is involved in the RNA stability, subcellular transport and synthesis of neuronal proteins associated with synapsis development, neuronal plasticity and brain development. The lack of FMRP protein results in dendritic spine dysmorphogenesis and an excitation/inhibition imbalance (Glutamate/GABA) that leads to weak synaptic connections due to which patient exhibit syndromic features (Saldarriaga et al., ). Biologically, FMRP is a translational repressor protein, and its dysfunction increases the rate of protein synthesis that includes both pre and post‐synaptic proteins (Bagni et al., ).…”

The Profiles and Correlates of Psychopathology in Adolescents and Adults with Williams, Fragile X and Prader–Willi Syndromes

“…The WS phenotype is characterised by hyper-sociability, hypersensitivity to sound (hyperacusis), attention deficits, impulsivity and emotional difficulties (Einfeld et al 1997;Jones et al 2000;Levitin et al 2005;Leyfer et al 2006). FXS is caused by a fMR1 gene mutation at Xq27.3, with a prevalence of 1 in 5000 men and 1 in 4000-6000 women (Coffee et al 2009;Saldarriaga et al 2014). Repetitive behaviour, attentional difficulties, social and sensory impairments and mental health problems such as anxiety are common (Garber et al 2008;McLennan et al 2011;Oakes et al 2016;Rogers et al 2003).…”