fragile X

see also:

• dementia

• genetic disorders caused by mutation of the Fragile X mental retardation 1 gene (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.
• some female carriers may experience ovarian insufficiency, which can cause irregular menstrual cycles, infertility and early menopause
• male and female carriers who do not have Fragile X syndrome, may still develop Fragile X Tremor Ataxia Syndrome when they age (see below)

• a late onset neurodegenerative disorder associated with problems with movement, memory, and the autonomic nervous system
• it is caused by a trinucleotide repeat disorder in the FMR1 gene.
• it most often occurs in men, but can present in women.

• intentional tremor
• ataxia
• Parkinsonism
• peripheral neuropathy
• Autonomic dysfunction and autonomic neuropathy causing hypertension, bladder/bowel dysfunction, impotence
• progressive dementia - diminishing short-term memory and executive function skills, declining math and spelling abilities and decision-making abilities
• limbic changes affecting personality - increased irritability, angry outbursts, and impulsive behaviour

• Fragile X syndrome is a genetic disorder caused by mutation of the FMR1 gene on the X-chromosome
  • Incidence of the disorder itself is about 1 in every 3600 males and 1 in 4000–6000 females
• it is the most commonly known single-gene cause of autism and the most common inherited cause of intellectual disability
• most females who have the syndrome experience symptoms to a lesser degree because of their second X-chromosome, however, they can develop symptoms just as severe as their male counterparts.
• full mutation males tend to present with severe intellectual disability
• other features include:
  • elongated face
  • large or protruding ears
  • flat feet
  • large testes (macroorchidism)
  • low muscle tone
  • hernias
  • pectus excavatum
  • high arched palate
  • puffy eyelids
  • cluttered speech or nervous speech
  • stereotypic movements (e.g. hand-flapping)
  • atypical social development, particularly shyness, limited eye contact, memory problems, and difficulty with face encoding
  • perseveration is a common communicative and behavioral characteristic
  • very short attention spans, are hyperactive, and show hypersensitivity to visual, auditory, tactile, and olfactory stimuli (ie. similar to ADHD)
  • ~30% meet the criteria for autism and FXS accounts for 2-6% of children with autism
  • from their 40s onward, males with FXS begin developing progressively more severe problems in performing tasks that require the central executive of working memory.