- Last edited on April 30, 2020
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child:genetic-disorders:fragile-x-syndrome-fxs [on April 12, 2019] |
child:genetic-disorders:fragile-x-syndrome-fxs [on January 28, 2021] (current) |
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| ===== Primer ===== | ===== Primer ===== | ||
| - | **Fragile X Syndrome (FXS)** is an X chromosome-linked dominant disorder caused by the amplification of a CGG repeat in the 5′ untranslated region of the fragile X mental retardation gene 1 (//FMR1//). It is the most common //inherited// cause of [[child:intellectual-disability:home|intellectual disability]]. | + | **Fragile X Syndrome (FXS)** is an X chromosome-linked dominant disorder caused by the amplification of a CGG repeat in the 5′ untranslated region of the fragile X mental retardation gene 1 (//FMR1//). It is the most common //inherited// cause of [[child:intellectual-disability|intellectual disability]], after Down syndrome.[([[https://pubmed.ncbi.nlm.nih.gov/17910090/|Sherman, S. L., Allen, E. G., Bean, L. H., & Freeman, S. B. (2007). Epidemiology of Down syndrome. Mental retardation and developmental disabilities research reviews, 13(3), 221-227.]])] |
| == Epidemiology == | == Epidemiology == | ||
| - | There is a prevalence of 1 in 3600 to 4000.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306413/|M Wadell, P., J Hagerman, R., & R Hessl, D. (2013). Fragile X syndrome: psychiatric manifestations, assessment and emerging therapies. Current psychiatry reviews, 9(1), 53-58.]])] | + | * There is a prevalence of 1 in 3600 to 4000.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306413/|M Wadell, P., J Hagerman, R., & R Hessl, D. (2013). Fragile X syndrome: psychiatric manifestations, assessment and emerging therapies. Current psychiatry reviews, 9(1), 53-58.]])] |
| + | * FXS is the most common //inherited// cause of intellectual disability ([[child:genetic-disorders:down-syndrome-trisomy-21|Down syndrome]] is the most common genetic cause of intellectual disability overall, but most cases occur sporadically and thus are not "inherited"). | ||
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| + | == Prognosis == | ||
| + | |||
| + | == Risk Factors == | ||
| == Comorbidity == | == Comorbidity == | ||
| - | Individuals have very high rates of anxiety disorders (over 80%), attention-deficit/hyperactivity disorder (over 50%), autism (30 to 35%), and mood instability and aggression.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306413/|M Wadell, P., J Hagerman, R., & R Hessl, D. (2013). Fragile X syndrome: psychiatric manifestations, assessment and emerging therapies. Current psychiatry reviews, 9(1), 53-58.]])] | + | * Individuals have very high rates of [[anxiety:home|anxiety disorders]] (over 80%), [[child:adhd|attention-deficit/hyperactivity disorder]] (over 50%), [[child:asd|autism]] (30 to 35%), and mood instability and aggression.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306413/|M Wadell, P., J Hagerman, R., & R Hessl, D. (2013). Fragile X syndrome: psychiatric manifestations, assessment and emerging therapies. Current psychiatry reviews, 9(1), 53-58.]])] |
| ===== Diagnosis ===== | ===== Diagnosis ===== | ||
| + | <callout icon="fa fa-lightbulb-o" type="success" title="Mnemonic"> | ||
| + | The mnemonic "e''**X**''tra large testes, jaws, and ears" can be used to remember the features of Fragile ''**X**'' Syndrome. | ||
| + | </callout> | ||
| ===== Pathophysiology ===== | ===== Pathophysiology ===== | ||
| + | * Fragile X is an X-linked dominant inheritance disorder. It is caused by a full mutation in the FMR1 gene. The FMR1 gene normally contains 5 to 44 trinucleotide repeats. "Premutation" carriers have about 55 to 200 trinucleotide repeats, while individuals with Fragile X have over 200 repeats. The excessive repeats lead to hypermethylation and silences expression of the gene. | ||
| + | * Since FXS affects the X chromosome, FXS predominantly affects males (since males only have one X chromosome). Females are less affected and and have greater variability in their phenotypic presentation (because they still have a normal X chromosome, in addition to the X with the mutation). | ||
| ===== Differential Diagnosis ===== | ===== Differential Diagnosis ===== | ||
| + | FXS can overlap with other disorders, such as autism, Prader-Willi syndrome, and attention-deficit/hyperactivity disorder (ADHD). | ||
| ===== Investigations ===== | ===== Investigations ===== | ||
| + | |||
| + | ===== Physical Exam ===== | ||
| + | On physical exam, individuals with FXS typically have: | ||
| + | * Long face with a large jaw, large everted ears | ||
| + | * Mitral valve prolapse | ||
| + | * Hypermobile joints | ||
| + | * Post-pubertal macroorchidism (enlarged testes) | ||
| ===== Treatment ===== | ===== Treatment ===== | ||
| ===== Resources ===== | ===== Resources ===== | ||
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| <WRAP group> | <WRAP group> | ||
| <WRAP quarter column> | <WRAP quarter column> | ||
| - | ==== For Patients ==== | + | == For Patients == |
| </WRAP> | </WRAP> | ||
| <WRAP quarter column> | <WRAP quarter column> | ||
| - | ==== For Providers ==== | + | == For Providers == |
| + | * **[[https://www.nature.com/articles/nrdp201765|Hagerman, R. J. et al. (2017). Fragile X syndrome. Nature reviews Disease primers, 3(1), 1-19.]]** | ||
| </WRAP> | </WRAP> | ||
| <WRAP quarter column> | <WRAP quarter column> | ||