II. Epidemiology
- Most common inherited Developmental Disability
- Full mutation
- Prevalence 1:4000 men and up to 1:6000 women
- Premutation in FMR1 gene carrier
- Prevalence 1:800 men and up to 1:100 women
- Diagnosis often not made until age 8
- Delayed diagnosis due to subtle features
III. Pathophysiology
- Fragile X Mutation (FMR1) Gene is on X Chromosome
- Expansion mutation in FMR1 Gene
- Occurs with repetitive CCG in FMR1
- Unaffected patients have <50 CCG repetitions
- Premutation carriers have 50-200 CCG repetitions
- Full mutation patients have >200 CCG repetitions
IV. Signs: Subtle Phenotype (milder in women)
- Facial features (onset in early childhood)
- Large prominent ears
- Long face or Macrocephaly
- Prominent forehead
- Macroorchidism (after Puberty)
-
Mental Retardation (80% of men, 33-65% of women)
- Moderate Mental Retardation (IQ <70)
-
Developmental Delay
-
Learning Disability
- Abstract reasoning
- Sequential processing
- Mathematics
- Delayed speech
- Males start to talk at 20 months
- Fine and gross motor coordination problems
- Males sit without support at 10 months
- Males start to walk at 20 months
-
Learning Disability
- Behavior problems
- Autistic-like characteristics
- Defensiveness
- Mood instability
- Speech Perseveration
- Anxiety
- Social problems
- Hand flapping
- Hand biting
- Gaze aversion
V. Associated conditions
- Epilepsy
- Strabismus
- Connective tissue dysplasia
- Hyperflexible joints
- Mitral Valve Prolapse
- Pes Planus
-
Attention Deficit Hyperactivity Disorder
- Affects 80% of fragile X patients
VI. Conditions associated with premutation carriers
- Premature Ovarian Failure (20% of women)
-
Fragile X-Associated Tremor-Ataxia Syndrome (FXTAS)
- Affects 30% men aged 50-60 years old
VII. Resources
- National Fragile X Foundation
- Fragile-X Research Foundation
- Gene Tests: FRM1-Related Disorders