Fragile X syndrome: Difference between revisions
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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> | 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> | ||
===History and Symptoms=== | ===History and Symptoms=== | ||
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> | |||
*Large and protruding ears | |||
*Elongated face | |||
*Macroorchidism (large testicles in men after puberty) | |||
*Flat foot | |||
*High Arched palate | |||
*Hyperflexible finger joints | |||
*Low muscle tone | |||
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> | |||
===Physical Examination=== | ===Physical Examination=== | ||
===Laboratory findings=== | ===Laboratory findings=== | ||
Revision as of 10:26, 15 July 2021
For patient information click here
| Fragile X syndrome | |
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| Location of FMR1 gene | |
| ICD-10 | Q99.2 |
| ICD-9 | 759.83 |
| OMIM | 309550 |
| DiseasesDB | 4973 |
| MeSH | D005600 |
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Fragile X syndrome Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Fragile X syndrome On the Web |
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American Roentgen Ray Society Images of Fragile X syndrome |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords:: Martin-bell syndrome; marker X syndrome, escalante's syndrome
Overview
Fragile x syndrome is the leading inherited cause of intellectual disorder and autism spectrum disorder with severe behavioral abnormalities . It is an X linked disorder, affecting both males and females. It is a genetic disease caused by CGG trinucleotide expansion (>200 CGG repeats).
Historical Perspective
Fragile X syndrome was described first by Martin and Bell in 1943. [1]
Classification
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. [2]
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.[3] In around 2% of cases, Fragile X syndrome can occur as a result of point mutation in FMR1 gene.[4]
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).[5]
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. [6] Fragile X Syndrome has been diagnosed in approximately 3 percent of boys with significant neurodevelopmental disorders. [7]
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. [8]
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. [9]
Natural History, Complications and Prognosis
Diagnosis
The diagnosis of Fragile X Syndrome is based upon detection of an alteration in the fragile X mental retardation 1 (FMR1) gene. [10]
History and Symptoms
The physical features of Fragile X syndrome is prominent around the time of puberty. Physical features include:[11]
- Large and protruding ears
- Elongated face
- Macroorchidism (large testicles in men after puberty)
- Flat foot
- High Arched palate
- Hyperflexible finger joints
- Low muscle tone
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).[12] Approximately, 20% of boy with Fragile X syndrome develops seizures (mostly simple or complex partial seizures)[13]
Physical Examination
Laboratory findings
Other diagnostic studies
Treatment
Medical Therapy | Primary Prevention | Secondary Prevention | Cost Effectiveness of Therapy | Future or Investigational Therapies
Case Studies
External links
Template:Pervasive developmental disorders Template:Chromosomal abnormalities
- ↑ Martin JP, Bell J. A pedigree of mental defect showing sex- linkage. J Neurol Psychiatry. 1943; 6(3-4): 154–7.
- ↑ 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
- ↑ Santoro MR, Bray SM, Warren ST (2012). "Molecular mechanisms of fragile X syndrome: a twenty-year perspective". Annu Rev Pathol. 7: 219–45. doi:10.1146/annurev-pathol-011811-132457. PMID 22017584.
- ↑ Peprah E (2012). "Fragile X syndrome: the FMR1 CGG repeat distribution among world populations". Ann Hum Genet. 76 (2): 178–91. doi:10.1111/j.1469-1809.2011.00694.x. PMC 3288311. PMID 22188182.
- ↑ Wiesner GL, Cassidy SB, Grimes SJ, Matthews AL, Acheson LS (2004). "Clinical consult: developmental delay/fragile X syndrome". Prim Care. 31 (3): 621–5, x. doi:10.1016/j.pop.2004.04.008. PMID 15331251.
- ↑ Coffee B, Keith K, Albizua I, Malone T, Mowrey J, Sherman SL; et al. (2009). "Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA". Am J Hum Genet. 85 (4): 503–14. doi:10.1016/j.ajhg.2009.09.007. PMC 2756550. PMID 19804849.
- ↑ McConkie-Rosell A, Finucane B, Cronister A, Abrams L, Bennett RL, Pettersen BJ (2005). "Genetic counseling for fragile x syndrome: updated recommendations of the national society of genetic counselors". J Genet Couns. 14 (4): 249–70. doi:10.1007/s10897-005-4802-x. PMID 16047089.
- ↑ 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
- ↑ Mak AS, Leung KY (2017). "Challenges in prenatal screening and counselling for fragile X syndrome". Hong Kong Med J. 23 (2): 108–9. doi:10.12809/hkmj175064. PMID 28387201.
- ↑ Ciaccio C, Fontana L, Milani D, Tabano S, Miozzo M, Esposito S (2017). "Fragile X syndrome: a review of clinical and molecular diagnoses". Ital J Pediatr. 43 (1): 39. doi:10.1186/s13052-017-0355-y. PMC 5395755. PMID 28420439.
- ↑ McLennan Y, Polussa J, Tassone F, Hagerman R (2011). "Fragile x syndrome". Curr Genomics. 12 (3): 216–24. doi:10.2174/138920211795677886. PMC 3137006. PMID 22043169.
- ↑ Fisch GS, Simensen R, Tarleton J, Chalifoux M, Holden JJ, Carpenter N; et al. (1996). "Longitudinal study of cognitive abilities and adaptive behavior levels in fragile X males: a prospective multicenter analysis". Am J Med Genet. 64 (2): 356–61. doi:10.1002/(SICI)1096-8628(19960809)64:2<356::AID-AJMG24>3.0.CO;2-D. PMID 8844080.
- ↑ Hagerman PJ, Stafstrom CE (2009). "Origins of epilepsy in fragile X syndrome". Epilepsy Curr. 9 (4): 108–12. doi:10.1111/j.1535-7511.2009.01309.x. PMC 2728488. PMID 19693328.