Fragile X Syndrome Flashcards
Percentage in population
50% of all X-linked metal retardation
0.6% of all metally retarded population
What is the 2nd most common cause of mental retardation in male
Fragile X syndrome
(Most common is Down syndrome)
Incidence rate in different sex
Male: 1 per 1000
Female: 1 per 3000
so, male are more affected
Type of genetic disorder
Trinucleotide (Triplet) repeat disorder
Mendelian Inheritence
Complex X-linked inheritence
(mainly X-linked dominant)
Abnormal Chromosome and gene
Long arm of X chromosome (Xq 27.3)
Gene: FMR1
Repeated triplets in Fragile X
CGG
Recall, Seen (C) Gross Guy
because, Fragile X has large testis, ear, head, jaw etc.
In normal individual, number of repeated triplets in the FMR1 gene
6 to 55 (stable inherited)
In premutation carriers, number of repeated triplets in the FMR1 gene
Between 55 and 230
(Premutation carriers are unaffected by fragile X syndrome)
In full mutation, number of repeated triplets in the FMR1 gene
230 to >1000 repeats (disease-causing range)
Who & when are more susceptible to full mutation of FMR1 gene?
Female prematuration carriers
During oogenesis
(So, Fragile X has maternal anticipation)
Are all full mutations affected by Fragile X syndrome?
NO
All males &
50% of females with full mutation are affected by Fragile X syndrome
(As it is more severe in male)
What is the special characteristic for being triplet disorder
Anticipation
What is anticipation
Earlier age of onset in successive generation +
increased severity of symptoms in them
Type of anticipation in Fragile X syndrome
Maternal anticipation
Features in the pre-mutation carriers (Male and female)
Pre-mutation carriers (55 to 230 CGG repeats in FMR1 gene)
Females:
- NO learning disability
- High risk of POF (Premature ovarian failure) [even more than normal or full mutation carriers]
Males:
- 3% develops Fragile X-associated tremor/ataxia syndrome > includes >
- At around 50years of age >>> parkinsonism + cognitive decline
Name 2 childhood diseases that can be present in a male baby with Fragile X
- Autism Spectrum disorder
- ADHD
Stature of of Fragile X
Shorter height
Cognitive features in Fragile X
- Learning difficulties
- Slow-off the mark
- Lack of social interaction
- Lack of concentration
- Low IQ
Facial features in Fragile X
- Long thin face
- Larger head
- Large forhead
- Strabismus
- Pale iris
- Large low set floppy ears
- High arched palate
- Large jaw (Prognathism)
Musculoskeletal features in fragile X
- Hypotonia
- Joint instability
Testicular change in Fragile X
Macro-orchidism: large testes
Cardiac defect in Fragile X
MVP (mitral valve prolapse)
Associated features
- Epilepsy (in 25%) (Seizures)
- Lower IQ (score: 35-45 among boys; 20-40among males)
- Cognitive deficit (30-50% of female carriers)
- Strabismus
- Otitis media
- Sinusitis
- Apnoea
- Joint dislocation
Investigation of choice (IOC)
Ante-natal: Chorionic villus sampling or amniocentesis
Chromosomal analysis: number of CGG repeats >> using ‘restriction endonuclease digestion’ and ‘southern-blot’ analysis
Genetic disorders with high arched palate
- Marfan syndrome
- Turner syndrome
- Fragile X syndrome
Genetic disorders with learning difficulties/mental retardation
- Most common: Down syndrome
- 2nd common: Fragile X syndrome
Genetic disorders with hypotonia
- Down syndrome
- Fragile X syndrome
Genetic disorders with mitral valve prolapse (late systolic murmur)
- Marfan syndrome
- Fragile X syndrome
Ear /Auricle change in Down syndrome and Fragile X syndrome
Down syndrome: small ears
Fragile X: large ears
Testes in Fragile X and Klinefelter syndrome
Fragile X: Large testes
Klinefelter syndrome: Small testes
