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| {{SK}}: Martin-bell syndrome; marker X syndrome, escalante's syndrome | | {{SK}}: Martin-bell syndrome; marker X syndrome, escalante's syndrome |
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| == [[Fragile X syndrome overview|Overview]] == | | ==[[Fragile X syndrome overview|Overview]]== |
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| == [[Fragile X syndrome historical perspective|Historical Perspective]] == | | ==[[Fragile X syndrome historical perspective|Historical Perspective]]== |
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| == [[Fragile X syndrome classification|Classification]] == | | ==[[Fragile X syndrome classification|Classification]]== |
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| == [[Fragile X syndrome pathophysiology|Pathophysiology]] == | | ==[[Fragile X syndrome pathophysiology|Pathophysiology]]== |
| Fragile x syndrome has an x-linked dominant inheritance. It is caused by an expansion of CGG trinucleotide repeat within FMR1 gene on X chromosome. Due to high number of CGG repeats (>200), this leads to methylation of part of gene on X chromosome that codes for Fragile X Mental retardation protein (FMRP), which is required for proper development of connections between neurons. <ref>1. fragile X syndrome - Genetics Home Reference [Internet]. 2016 [cited 2021 Jul 15]. Available from: https://web.archive.org/web/20161009162713/https://ghr.nlm.nih.gov/condition/fragile-x-syndrome </ref>
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| == [[Fragile X syndrome causes|Causes]] == | | ==[[Fragile X syndrome causes|Causes]]== |
| Fragile x Syndrome is a genetic disease which is caused by mutation in the Fragile x Mental Retardation 1(FMR1) gene in X chromosome. Generally, these mutation (>200 repeats of CGG) occurs at in the 5' untranslated region of FMR1.<ref name="pmid22017584">{{cite journal| author=Santoro MR, Bray SM, Warren ST| title=Molecular mechanisms of fragile X syndrome: a twenty-year perspective. | journal=Annu Rev Pathol | year= 2012 | volume= 7 | issue= | pages= 219-45 | pmid=22017584 | doi=10.1146/annurev-pathol-011811-132457 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22017584 }} </ref> In around 2% of cases, Fragile X syndrome can occur as a result of point mutation in FMR1 gene.<ref name="pmid22188182">{{cite journal| author=Peprah E| title=Fragile X syndrome: the FMR1 CGG repeat distribution among world populations. | journal=Ann Hum Genet | year= 2012 | volume= 76 | issue= 2 | pages= 178-91 | pmid=22188182 | doi=10.1111/j.1469-1809.2011.00694.x | pmc=3288311 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22188182 }} </ref>
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| == [[Fragile X syndrome differential diagnosis|Differentiating Fragile X syndrome from other Diseases]] == | | ==[[Fragile X syndrome differential diagnosis|Differentiating Fragile X syndrome from other Diseases]]== |
| Fragile X syndrome must be differentiated from Autism Spectrum Disorder, Attention deficit hyperactivity disorder (ADHD), Fragile XE syndrome (FRAXE), Klinefelter syndrome and Prader-Willi syndrome (PWS).<ref name="pmid15331251">{{cite journal| author=Wiesner GL, Cassidy SB, Grimes SJ, Matthews AL, Acheson LS| title=Clinical consult: developmental delay/fragile X syndrome. | journal=Prim Care | year= 2004 | volume= 31 | issue= 3 | pages= 621-5, x | pmid=15331251 | doi=10.1016/j.pop.2004.04.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15331251 }} </ref>
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| == [[Fragile X syndrome epidemiology and demographics|Epidemiology and Demographics]] == | | ==[[Fragile X syndrome epidemiology and demographics|Epidemiology and Demographics]]== |
| The prevalence of Fragile X syndrome is approximately 1 in 5000 men and 1 in 4000-6000 women worldwide, determined by molecular assays. <ref name="pmid19804849">{{cite journal| author=Coffee B, Keith K, Albizua I, Malone T, Mowrey J, Sherman SL | display-authors=etal| title=Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA. | journal=Am J Hum Genet | year= 2009 | volume= 85 | issue= 4 | pages= 503-14 | pmid=19804849 | doi=10.1016/j.ajhg.2009.09.007 | pmc=2756550 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19804849 }} </ref>
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| Fragile X Syndrome has been diagnosed in approximately 3 percent of boys with significant neurodevelopmental disorders. <ref name="pmid16047089">{{cite journal| author=McConkie-Rosell A, Finucane B, Cronister A, Abrams L, Bennett RL, Pettersen BJ| title=Genetic counseling for fragile x syndrome: updated recommendations of the national society of genetic counselors. | journal=J Genet Couns | year= 2005 | volume= 14 | issue= 4 | pages= 249-70 | pmid=16047089 | doi=10.1007/s10897-005-4802-x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16047089 }} </ref>
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| == [[Fragile X syndrome risk factors|Risk Factors]] == | | ==[[Fragile X syndrome risk factors|Risk Factors]]== |
| There are no established risk factors for Fragile X syndrome. However, the child with family history of Fragile x Syndrome, autism disorder of unknown cause, developmental delay, adult onset ataxia/tremor or any intellectual disabilities are at greater risk of developing the disorder. <ref> 1. Carrier Testing for Fragile X Syndrome [Internet]. ucsfhealth.org. [cited 2021 Jul 15]. Available from: https://www.ucsfhealth.org/Education/Carrier Testing for Fragile X Syndrome </ref>
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| == [[Fragile X syndrome screening|Screening]] == | | ==[[Fragile X syndrome screening|Screening]]== |
| Genetic counseling and prenatal screening is recommended when one of the parents is shown to be a carrier of fragile X. Prenatal testing can be done by amniocentesis at 16-20 weeks or by chorionic villus sampling (CVS) at 10-13 weeks to determine if a fetus has inherited the fragile X gene. <ref name="pmid28387201">{{cite journal| author=Mak AS, Leung KY| title=Challenges in prenatal screening and counselling for fragile X syndrome. | journal=Hong Kong Med J | year= 2017 | volume= 23 | issue= 2 | pages= 108-9 | pmid=28387201 | doi=10.12809/hkmj175064 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28387201 }} </ref>
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| == [[Fragile X syndrome natural history, complications and prognosis|Natural History, Complications and Prognosis]] == | | ==[[Fragile X syndrome natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| == Diagnosis ==
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| The diagnosis of Fragile X Syndrome is based upon detection of an alteration in the fragile X mental retardation 1 (FMR1) gene. <ref name="pmid28420439">{{cite journal| author=Ciaccio C, Fontana L, Milani D, Tabano S, Miozzo M, Esposito S| title=Fragile X syndrome: a review of clinical and molecular diagnoses. | journal=Ital J Pediatr | year= 2017 | volume= 43 | issue= 1 | pages= 39 | pmid=28420439 | doi=10.1186/s13052-017-0355-y | pmc=5395755 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28420439 }} </ref>
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| ===History and Symptoms===
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| The physical features of Fragile X syndrome is prominent around the time of puberty. Physical features include:<ref name="pmid22043169">{{cite journal| author=McLennan Y, Polussa J, Tassone F, Hagerman R| title=Fragile x syndrome. | journal=Curr Genomics | year= 2011 | volume= 12 | issue= 3 | pages= 216-24 | pmid=22043169 | doi=10.2174/138920211795677886 | pmc=3137006 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22043169 }} </ref>
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| *Large and protruding ears
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| *Elongated face
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| *Macroorchidism (large testicles in men after puberty)
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| *Flat foot
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| *High Arched palate
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| *Hyperflexible finger joints
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| *Low muscle tone
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| The common features in child with Fragile X Syndrome include low IQ with learning difficulties (intellectual disabilities). Behavioral abnormalities includes stereotypic movements (e.g., hand-flapping) hyperactivity, inattention, poor social interaction, limited eye contact and poor memory. Child with Fragile X syndrome often presents with developmental delay (including delayed attainment of motor and language milestones).<ref name="pmid8844080">{{cite journal| author=Fisch GS, Simensen R, Tarleton J, Chalifoux M, Holden JJ, Carpenter N | display-authors=etal| title=Longitudinal study of cognitive abilities and adaptive behavior levels in fragile X males: a prospective multicenter analysis. | journal=Am J Med Genet | year= 1996 | volume= 64 | issue= 2 | pages= 356-61 | pmid=8844080 | doi=10.1002/(SICI)1096-8628(19960809)64:2<356::AID-AJMG24>3.0.CO;2-D | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8844080 }} </ref> Approximately, 20% of boy with Fragile X syndrome develops seizures (mostly simple or complex partial seizures)<ref name="pmid19693328">{{cite journal| author=Hagerman PJ, Stafstrom CE| title=Origins of epilepsy in fragile X syndrome. | journal=Epilepsy Curr | year= 2009 | volume= 9 | issue= 4 | pages= 108-12 | pmid=19693328 | doi=10.1111/j.1535-7511.2009.01309.x | pmc=2728488 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19693328 }} </ref>
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| ===Physical Examination=== | | ===[[History and Symptoms]]=== |
| ===Laboratory findings===
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| ===Other diagnostic studies===
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| == Treatment == | | ===Physical Examination=== |
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| | ===[[Laboratory findings]]=== |
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| | ===[[Other diagnostic studies]]=== |
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| | ==Treatment== |
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| [[Fragile X syndrome medical therapy|Medical Therapy]] | [[Fragile X syndrome primary prevention|Primary Prevention]] | [[Fragile X syndrome secondary prevention|Secondary Prevention]] | [[Fragile X syndrome cost-effectiveness of therapy|Cost Effectiveness of Therapy]] | [[Fragile X syndrome future or investigational therapies|Future or Investigational Therapies]] | | [[Fragile X syndrome medical therapy|Medical Therapy]] | [[Fragile X syndrome primary prevention|Primary Prevention]] | [[Fragile X syndrome secondary prevention|Secondary Prevention]] | [[Fragile X syndrome cost-effectiveness of therapy|Cost Effectiveness of Therapy]] | [[Fragile X syndrome future or investigational therapies|Future or Investigational Therapies]] |
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| ==External links== | | ==External links== |
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| *[http://www.cdc.gov/ncbddd/single_gene/fragilex.htm CDC’s National Center on Birth Defects and Developmental Disabilities] | | *[http://www.cdc.gov/ncbddd/single_gene/fragilex.htm CDC’s National Center on Birth Defects and Developmental Disabilities] |
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