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Fragile X SyndromeAka: Fragile X Mental Retardation 1 Gene, FMR1, Premutation in FMR1

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  1. Epidemiology
    1. Most common inherited developmental Disability
    2. Full mutation
      1. Prevalence 1:4000 men and up to 1:6000 women
    3. Premutation in FMR1 gene carrier
      1. Prevalence 1:800 men and up to 1:100 women
    4. Diagnosis often not made until age 8
      1. Delayed diagnosis due to subtle features
  2. Pathophysiology
    1. Fragile X Mutation (FMR1) Gene is on X Chromosome
    2. Expansion mutation in FMR1 Gene
      1. Occurs with repetitive CCG in FMR1
      2. Unaffected patients have <50 CCG repetitions
      3. Premutation carriers have 50-200 CCG repetitions
      4. Full mutation patients have >200 CCG repetitions
  3. Signs: Subtle phenotype (milder in women)
    1. Facial features (onset in early childhood)
      1. Large prominent ears
      2. Long face or Macrocephaly
      3. Prominent forehead
    2. Macroorchidism (after Puberty)
    3. Mental Retardation (80% of men, 33-65% of women)
      1. Moderate mental retardation (IQ <70)
    4. Developmental Delay
      1. Learning Disability
        1. Abstract reasoning
        2. Sequential processing
        3. Mathematics
      2. Delayed speech
        1. Males start to talk at 20 months
      3. Fine and gross motor coordination problems
        1. Males sit without support at 10 months
        2. Males start to walk at 20 months
    5. Behavior problems
      1. Autistic-like characteristics
      2. Defensiveness
      3. Mood instability
      4. Speech perseveration
      5. Anxiety
      6. Social problems
      7. Hand flapping
      8. Hand biting
      9. Gaze aversion
  4. Associated conditions
    1. Epilepsy
    2. Strabismus
    3. Connective tissue dysplasia
      1. Hyperflexible joints
      2. Mitral Valve Prolapse
      3. Pes planus
    4. Attention Deficit Hyperactivity Disorder
      1. Affects 80% of fragile X patients
  5. Conditions associated with premutation carriers
    1. Premature Ovarian Failure (20% of women)
    2. Fragile X-Associated Tremor-Ataxia Syndrome (FXTAS)
      1. Affects 30% men aged 50-60 years old
  6. Resources
    1. National Fragile X Foundation
      1. http://www.FragileX.org
    2. Fragile-X Research Foundation
      1. http://fraxa.org
    3. Gene Tests: FRM1-Related Disorders
      1. http://www.geneclinics.org/profiles/fragilex/
  7. References
    1. Wattendorf (2005) Am Fam Physician 72:111
    2. Visootsak (2005) Clin Pediatr 44:371

FMR1 gene (C1414649)

ConceptsGene or Genome (T028)
EnglishFMR1, FMR1 gene, FMRP, fragile X mental retardation 1, FRAGILE X MENTAL RETARDATION PROTEIN, FRAXA, MGC87458
SourcesHUGO, LNC, MTH, OMIM
Derived from the NIH UMLS (Unified Medical Language System)



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