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Encyclopedia > Fragile X syndrome
Fragile X syndrome
Classification & external resources
Location of FMR1 gene
ICD-10 Q99.2
ICD-9 759.83
OMIM 309550
DiseasesDB 4973
eMedicine ped/800 
MeSH D005600

Fragile X syndrome is a syndrome of X-linked mental retardation. Boys with the syndrome may have large testicles (macroorchidism), prognathism, hypotonia and autism, and a characteristic but variable face with large ears, long face, high-arched palate, gynecomastia, and malocclusion. Additional abnormalities may include lordosis, heart defect, pectus excavatum, flat feet, shortening of the tubular bones of the hands, and joint laxity. Females who have one fragile chromosome and one normal X chromosome may range from normal to mild manifestations of the fragile X syndrome. The fragile X syndrome has an estimated incidence of 1 in 3600 males and 1 in 4,000–6,000 females. [1] Image File history File links Fmr1. ... Location of FMR1 on the X chromosome FMR1 (fragile X mental retardation 1) is a human gene that provides instructions to make a protein called fragile X mental retardation 1, or FMRP. This protein is normally made in many tissues, especially in the brain and testes. ... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // Q00-Q99 - Congenital malformations, deformations and chromosomal abnormalities (Q00-Q07) Congenital malformations of the nervous system (Q00) Anencephaly and similar malformations (Q01) Encephalocele (Q02) Microcephaly (Q03) Congenital hydrocephalus (Q04) Other congenital malformations of brain (Q05) Spina bifida (Q06) Other congenital malformations of spinal cord (Q07) Other congenital malformations of nervous... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... In medicine, the term syndrome is the association of several clinically recognizable features, signs, symptoms, phenomena or characteristics which often occur together, so that the presence of one feature alerts the physician to the presence of the others. ... Sex-linked genes are those carried on the mammalian X chromosome but not the Y chromosome. ... Mental retardation is a term for a pattern of persistently slow learning of basic motor and language skills (milestones) during childhood, and a significantly below-normal global intellectual capacity as an adult. ... Abnormally large testes commonly attributed with fragile X syndrome, the most common inherited form of mental retardation. ... This article or section is in need of attention from an expert on the subject. ... Hypotonia is a condition of abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. ... Autism is a brain development disorder characterized by impairments in social interaction and communication, and restricted and repetitive behavior, all exhibited before a child is three years old. ... The palate is the roof of the mouth in humans and vertebrate animals. ... Gynecomastia, or gynaecomastia, pronounced is the development of abnormally large mammary glands in males resulting in breast enlargement, which can sometimes cause secretion of milk. ... A malocclusion refers to the misalignment of teeth and/or incorrect relation between the teeth of the two dental arches. ... Lordosis is a term used to describe the direction of the curvature of the five lumbar and seven cervical vertebrae of the vertebral column. ... Pectus excavatum is a congenital deformity (often present at birth) of the sternum, which is pressed into the chest, resulting in a caved-in or sunken appearance. ... Flat feet, also called pes planus or fallen arches, is a condition in which the arch of the foot collapses, with the entire sole of the foot coming into complete or near-complete contact with the ground. ...

Contents

History

Martin and Bell in 1943, described a pedigree of X-linked mental disability, without considering the macroorchidism.[2] In 1969 Herbert Lubs first sighted an unusual "marker X chromosome" in association with mental disability.[3] In 1970 Frederick Hecht coined the term "fragile site" (Renpenning's syndrome is not synonymous with the Martin-Bell (fragile X) syndrome). In Renpennig's syndrome there is no fragile site on the X chromosome. Renpenning’s cases had short stature, moderate microcephaly, and neurological disorders.


Escalante's syndrome is synonymous with the fragile X syndrome. This term has been used in Brazil and other South American countries.


Causes

X-linked recessive inheritance
X-linked recessive inheritance

The fragile X syndrome is a genetic disorder caused by mutation of the FMR1 gene on the X chromosome. Mutation at that site is found in 1 out of about every 2000 males and 1 out of about every 259 females. (Incidence of the disease itself is about 1 in every 4000 females.) X-linked Recessive inheritance From http://ghr. ... A genetic disorder is a disease caused by abnormalities in genes or chromosomes. ... It has been suggested that mutant be merged into this article or section. ... Location of FMR1 on the X chromosome FMR1 (fragile X mental retardation 1) is a human gene that provides instructions to make a protein called fragile X mental retardation 1, or FMRP. This protein is normally made in many tissues, especially in the brain and testes. ... For a non-technical introduction to the topic, see Introduction to Genetics. ... ‹ The template below (Expand) is being considered for deletion. ... The shield and spear of the Roman god Mars, which is also the alchemical symbol for iron, represents the male sex. ... Look up Female in Wiktionary, the free dictionary. ...


Normally, the FMR1 gene contains between 6 and 55 repeats of the CGG codon (trinucleotide repeats). In people with the fragile X syndrome, the FMR1 allele has over 230 repeats of this codon. Location of FMR1 on the X chromosome FMR1 (fragile X mental retardation 1) is a human gene that provides instructions to make a protein called fragile X mental retardation 1, or FMRP. This protein is normally made in many tissues, especially in the brain and testes. ... RNA codons. ... Trinucleotide repeat disorders (also known as trinucleotide repeat expansion disorders, expansion disorders or codon reiteration disorders) are due to stretches of DNA in a gene that contain the same trinucleotide sequence repeated many times. ... For the hard rock band, see Allele (band). ...


Expansion of the CGG repeating codon to such a degree results in a methylation of that portion of the DNA, effectively silencing the expression of the FMR1 protein. DNA methylation is a type of chemical modification of DNA that can be inherited without changing the DNA sequence. ... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ...


This methylation of the FMR1 locus in chromosome band Xq27.3 is believed to result in constriction of the X chromosome which appears 'fragile' under the microscope at that point, a phenomenon that gave the syndrome its name. Figure 1: A representation of a condensed eukaryotic chromosome, as seen during cell division. ...


Mutation of the FMR1 gene leads to the transcriptional silencing of the fragile X-mental retardation protein, FMRP. In normal individuals, FMRP binds and facilitates the translation of a number of essential neuronal RNAs. In fragile X patients, however, these RNAs are not translated into proteins. Location of FMR1 on the X chromosome FMR1 (fragile X mental retardation 1) is a human gene that provides instructions to make a protein called fragile X mental retardation 1, or FMRP. This protein is normally made in many tissues, especially in the brain and testes. ... Neurons (also called nerve cells) are the primary cells of the nervous system. ... Ribonucleic acid or RNA is a nucleic acid polymer consisting of nucleotide monomers that plays several important roles in the processes that translate genetic information from deoxyribonucleic acid (DNA) into protein products; RNA acts as a messenger between DNA and the protein synthesis complexes known as ribosomes, forms vital portions...


Transmission of the Fragile X

The diagram (right) of X-linked recessive inheritance is not entirely inappropriate but it markedly oversimplifies the situation and does not provide a sufficient foundation for genetic counseling about the fragile X syndrome. Technically, fragile X syndrome is an X-linked dominant condition with reduced penetrance.


Because males normally have only one copy of the X chromosome, those males with significant trinucleotide expansion at the FMR1 locus are symptomatic. They are intellectually disabled and may show various physical features of the fragile X syndrome.


Females have two X chromosomes and thus have double the chance of having a working FMR1 allele. Females carrying one X chromosome with an expanded FMR1 gene can have some signs and symptoms of the disorder or be normal. Although the extra X chromosome can serve as a backup, only one X chromosome is active at a time due to X-inactivation. For the hard rock band, see Allele (band). ... In those species in which sex is determined by the presence of the Y or W chromosome rather than the diploidy of the X or Z, a Barr body is the inactive X chromosome in a female cell, or the inactive Z in a male. ...


Males with the fragile X cannot transmit it to any of their sons (since males contribute a Y chromosome, not an X, to their male offspring), but will transmit it to all of their daughters, as males contribute their X to all of their daughters.


Females carrying one copy of the fragile X can transmit it to their sons or daughters; in this case each child has a 50% chance of inheriting the fragile X. Sons who receive the fragile X are at high risk of intellectual disability. Daughters who receive the fragile X may appear normal or they may be intellectually disabled, usually to a lesser degree than boys with the syndrome. The transmission of fragile X often increases with each passing generation. This seemingly anomalous pattern of inheritance is referred to as the Sherman paradox. The Sherman Paradox refers to an anomalous pattern of inheritance found in Fragile X syndrome. ...


Symptoms

Prominent characteristics of the syndrome include an elongated face, large or protruding ears, and low muscle tone.
Prominent characteristics of the syndrome include an elongated face, large or protruding ears, and low muscle tone.

Aside from intellectual disability, prominent characteristics of the syndrome include an elongated face, large or protruding ears, flat feet, larger testicles in men (macroorchidism), and low muscle tone. Speech may include cluttered speech or nervous speech[4]. Behavioral characteristics may include stereotypic movements (e.g., hand-flapping) and atypical social development, particularly shyness and limited eye contact. Some individuals with the fragile X syndrome also meet the diagnostic criteria for autism. Most females experience symptoms to a lesser degree because of their second X-chromosome, however they can develop just as severe symptoms. While full mutation males tend to present with severe intellectual disability, the symptoms of full mutation females runs the gamut of minimally affected to severe intellectual disability, which may explain why females are underdiagnosed relative to males. Image File history File links Download high-resolution version (583x694, 91 KB) From: Jean-no illustrations JNL The w:en:Fragile X syndrome common physical symptoms : elongated face, large ears, etc. ... Image File history File links Download high-resolution version (583x694, 91 KB) From: Jean-no illustrations JNL The w:en:Fragile X syndrome common physical symptoms : elongated face, large ears, etc. ... Hypotonia is a medical term that refers to a condition of abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). ... Abnormally large testes commonly attributed with fragile X syndrome, the most common inherited form of mental retardation. ... Hypotonia is a medical term that refers to a condition of abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). ... Cluttered speech is a common term for speech that becomes broken down, cluttered, or unintelligible due to a variety of reasons. ...


Diagnosis

Fragile X syndrome was originally diagnosed by culturing cells in a folate deficient medium and then assessing the cultures for X-chromosome breakage by cytogenetic analysis of the long arm of the X chromosome. This technique proved unreliable for both diagnosis and carrier testing. A metaphase cell positive for the bcr/abl rearrangement using FISH Cytogenetics is the study of the structure of chromosome material. ...


The fragile X abnormality is now directly determined by analysis of the number of CGG repeats and their methylation status using restriction endonuclease digestion and Southern blot analysis. A restriction enzyme (or restriction endonuclease) is an enzyme that cuts double-stranded DNA. The enzyme makes two incisions, one through each of the phosphate backbones of the double helix without damaging the bases. ... A Southern blot is a method routinely used in molecular biology to check for the presence of a DNA sequence in a DNA sample. ...


Treatment and current research

Recent studies have focused on a number of critical areas. The role of FMRP's RNA partners, many of which have now been validated through in vitro assays, is of primary importance. Also being examined is the function the various domains of FMRP, an RNA-binding protein, which is still relatively unknown. Wiktionary has a definition of: In vitro In vitro (Latin: within glass) means within a test tube, or, more generally, outside a living organism or cell. ... RNA-binding proteins are typically cytoplasmic and nuclear proteins that associate with (bind) and facilitate the translation of RNAs. ...


While there is no current cure for the syndrome, there is hope that further understanding of its underlying causes would lead to new therapies. Currently, the syndrome can be treated through behavioral therapy, special education, medication, and when necessary, treatment of physical abnormalities. Persons with the fragile X syndrome in their family histories are advised to seek genetic counseling to assess the likelihood of having children who are affected, and how severe any impairments may be in affected descendants. Cognitive therapy or cognitive behavior therapy is a kind of psychotherapy used to treat depression, anxiety disorders, phobias, and other forms of mental disorder. ... Special education is instruction that is modified or particularized for those students with special needs, such as learning differences, mental health problems, specific disabilities (physical or developmental) [1] , and giftedness [2]. // Children with special needs have always been part of society. ... Genetic counseling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning in order to prevent, avoid or...


Researchers at the Picower Institute for Learning and Memory at MIT have reversed symptoms of mental retardation and autism in mice.[5]


References

  1. ^ Crawford, D.C.; Acuna, J.M. & Sherman, S.L. (2001) "FMR1 and the Fragile X syndrome: Human genome epidemiology review". Genet Med 3: 359-371
  2. ^ Martin, J. P. & Bell, J. "A pedigree of mental defect showing sex-linkage". Journal of neurology, neurosurgery, and psychiatry (J. Neurol. Psychiat.). BMJ Publishing Group, London 6.1943, 154-157. ISSN 0022-3050
  3. ^ Lubs, H. (1969) "A marker X chromosome". Am Hum Genet 21: 231.
  4. ^ http://www.wrongdiagnosis.com/f/fragile_x_syndrome/signs.htm
  5. ^ MIT researchers reverse symptoms in mice of leading inherited cause of mental retardation

ISSN, or International Standard Serial Number, is the unique eight-digit number applied to a periodical publication including electronic serials. ...

External links

  • CDC’s National Center on Birth Defects and Developmental Disabilities
  • FraXA.org - The Fragile X Research Foundation
  • http://www.fragilex.org.uk/index.asp - The United Kingdom National Fragile X charity
  • FragileX.org - The National Fragile X Foundation (US) - Support, Awareness, Education, Research and Advocacy since 1984
  • The Colorado Fragile X Consortium
  • Stanford.edu - 'Trinucleotide Repeat Disorders Part 9: Non-Polyglutamine Diseases: Descriptions of other diseases that involve codon repeat expansions' (September 18, 2002)
  • Genetics of Fragile X Syndrome
  • Gene Reviews

This article or section does not cite any references or sources. ... There are many comorbid disorders associated with autism spectrum disorders and Aspergers Syndrome. ... The heritability of autism is debated by psychology researchers, parents of children diagnosed with autism, and members of the autistic community. ... The reported incidence of autism varies considerably among countries and is complicated by varying criteria for diagnosing autism, different standards for reporting public health problems, and other possible variations. ... Autism (also called autistic disorder, infantile autism, Kanners syndrome or Kanner syndrome) is a neurodevelopmental disorder that manifests itself before the age of three years. ... It has been suggested that this article or section be merged with Biomedical intervention for autism. ... Asperger syndrome (also referred to as Aspergers syndrome, Aspergers disorder, Aspergers, or AS) is one of five neurobiological pervasive developmental disorders (PDD), and is characterized by deficiencies in social and communication skills, normal to above normal intelligence,[1] and standard language development. ... Autism is a brain development disorder characterized by impairments in social interaction and communication, and restricted and repetitive behavior, all exhibited before a child is three years old. ... Childhood disintegrative disorder (CDD), also known as Hellers syndrome and disintegrative psychosis, is a rare condition characterized by late onset (>3 years of age) of developmental delays in language, social function, and motor skills. ... Hyperlexia is a syndrome in which the main characteristics are an above normal ability to read coupled with a below normal ability to understand spoken language. ... Multiple-complex Developmental Disorder (McDD) represents a distinct group within the autistic spectrum based on symptomatology. ... PDD not otherwise specified or PDD-NOS is a pervasive developmental disorder. ... A woman with Retts Syndrome Rett syndrome is a neurodevelopmental disorder that is classified as a pervasive developmental disorder by the DSM-IV. Many [1] argue that this is a mis-classification just as it would be to include such disorders as fragile X syndrome, tuberous sclerosis, or Down... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... It has been suggested that Sensory processing disorder be merged into this article or section. ... There is considerable disagreement over the exact nature of autism, however it is generally considered to be a neurodevelopmental condition which manifests itself in markedly abnormal social interaction, communication ability, patterns of interests, and patterns of behavior. ... Andrew Wakefield (born 1956 in the United Kingdom) is a Canadian trained surgeon, best known as the lead author of a controversial 1998 research study, published in The Lancet, which reported bowel symptoms in a selected sample of twelve children with autistic spectrum disorders and other disabilities, and alleged a... The autism rights movement (which has also been called autistic self-advocacy movement [1] and autistic liberation movement [2]) was started by adult autistic individuals in order to advocate and demand tolerance for what they refer to as neurodiversity. ... Autistic enterocolitis is a controversial condition first reported by British gastroenterologist Dr. Andrew Wakefield to describe a number of common clinical symptoms and signs which he contends is distinctive to autism. ... Biomedical intervention for autism consists of a wide range of therapeutic approaches for treating - and some say curing - autism in children, adolescents, and possibly adults. ... Chelation therapy is a process involving the use of chelating agents to remove heavy metals from the body. ... Ethical challenges to autism treatment have been made by people who feel that autism therapies intended to be helpful are actually harmful to autistic people. ... There are many controversies about functioning labels in the autism spectrum. ... Generation Rescue is a nonprofit organization which was founded by parents united by their belief that many childhood neurological disorders, such as autism, Aspergers syndrome, ADHD, speech delay, sensory integration disorder and other developmental delays, are the effects of a primary diagnosis of mercury poisoning and related complications. ... Neurodiversity is an idea that asserts that atypical (neurodivergent) neurological wiring is a normal human difference that is to be tolerated and respected as any other human difference. ... The term refrigerator mother was coined in the 1940s as a label for mothers of autistic children. ... This is a list of autism-related topics. ... Fictional characters described by the authors as having conditions on the autistic spectrum. ... Further reading on the topic of Asperger syndrome: [Attwood, Tony]; foreword by Lorna Wing (1998). ... This is a list of noteworthy people known to have a condition on the autistic spectrum. ... A number of famous people have been speculated by reputable sources to have had autistic disorder or Asperger syndrome. ... Infinity logo as a positive representation of autism Aspies For Freedom is a group which is at the forefront of the autism rights movement. ... Cure Autism Now, or CAN, is an American organization dedicated to finding a cure for autism by accelerating the pace of biomedical research in autism through fundraising for research projects, education and outreach. ... The National Alliance for Autism Research, based in Princeton, New Jersey, is a non-profit advocacy organization, founded by parents of children with autism concerned about the limited funding available for research. ...   Wrong Planet (sometimes referred to by its URL, WrongPlanet. ...


  Results from FactBites:
 
fragile X syndrome: Definition and Much More from Answers.com (4526 words)
Fragile X syndrome inherited in an X-linked dominant manner (characters are transmitted by genes on the X chromosome).
The fragile X syndrome is a genetic disorder caused by mutation of the FMR1 gene on the X chromosome.
Fragile X syndrome was originally diagnosed by culturing cells in a folate deficient medium and then assessing the cultures for X-chromosome breakage by cytogenetic analysis of the long arm of the X chromosome.
Fragile X Syndrome- Health Encyclopedia and Reference (715 words)
Fragile X syndrome is an X chromosome defect that causes mental retardation and a wide range of associated signs and symptoms.
Most of the time these fragile sites are not associated with medical problems, but a pronounced gap in one such region, at the end of the long arm of the X chromosome is associated with fragile X syndrome.
Fragile X syndrome is estimated to affect one in 2,000 males and to be responsible for 10 percent of mentally retarded males.
  More results at FactBites »

 
 

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