Fragile X Syndrome

Question 1

Percentage in population

Answer 1

50% of all X-linked metal retardation

0.6% of all metally retarded population

Question 2

What is the 2nd most common cause of mental retardation in male

Answer 2

Fragile X syndrome

(Most common is Down syndrome)

Question 3

Incidence rate in different sex

Answer 3

Male: 1 per 1000

Female: 1 per 3000

so, male are more affected

Question 4

Type of genetic disorder

Answer 4

Trinucleotide (Triplet) repeat disorder

Question 5

Mendelian Inheritence

Answer 5

Complex X-linked inheritence

(mainly X-linked dominant)

Question 6

Abnormal Chromosome and gene

Answer 6

Long arm of X chromosome (Xq 27.3)

Gene: FMR1

Question 7

Repeated triplets in Fragile X

Answer 7

CGG

Recall, Seen (C) Gross Guy

because, Fragile X has large testis, ear, head, jaw etc.

Question 8

In normal individual, number of repeated triplets in the FMR1 gene

Answer 8

6 to 55 (stable inherited)

Question 9

In premutation carriers, number of repeated triplets in the FMR1 gene

Answer 9

Between 55 and 230

(Premutation carriers are unaffected by fragile X syndrome)

Question 10

In full mutation, number of repeated triplets in the FMR1 gene

Answer 10

230 to >1000 repeats (disease-causing range)

Question 11

Who & when are more susceptible to full mutation of FMR1 gene?

Answer 11

Female prematuration carriers

During oogenesis

(So, Fragile X has maternal anticipation)

Question 12

Are all full mutations affected by Fragile X syndrome?

Answer 12

NO

All males &

50% of females with full mutation are affected by Fragile X syndrome

(As it is more severe in male)

Question 13

What is the special characteristic for being triplet disorder

Answer 13

Anticipation

Question 14

What is anticipation

Answer 14

Earlier age of onset in successive generation +

increased severity of symptoms in them

Question 15

Type of anticipation in Fragile X syndrome

Answer 15

Maternal anticipation

Question 16

Features in the pre-mutation carriers (Male and female)

Answer 16

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

Question 17

Name 2 childhood diseases that can be present in a male baby with Fragile X

Answer 17

• Autism Spectrum disorder
• ADHD

Question 18

Stature of of Fragile X

Answer 18

Shorter height

Question 19

Cognitive features in Fragile X

Answer 19

• Learning difficulties
• Slow-off the mark
• Lack of social interaction
• Lack of concentration
• Low IQ

Question 20

Facial features in Fragile X

Answer 20

• Long thin face
• Larger head
• Large forhead
• Strabismus
• Pale iris
• Large low set floppy ears
• High arched palate
• Large jaw (Prognathism)

Question 21

Musculoskeletal features in fragile X

Answer 21

• Hypotonia
• Joint instability

Question 22

Testicular change in Fragile X

Answer 22

Macro-orchidism: large testes

Question 23

Cardiac defect in Fragile X

Answer 23

MVP (mitral valve prolapse)

Question 24

Associated features

Answer 24

• 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

Question 25

Investigation of choice (IOC)

Answer 25

Ante-natal: Chorionic villus sampling or amniocentesis

Chromosomal analysis: number of CGG repeats >> using ‘restriction endonuclease digestion’ and ‘southern-blot’ analysis

Question 26

Genetic disorders with high arched palate

Answer 26

• Marfan syndrome
• Turner syndrome
• Fragile X syndrome

Question 27

Genetic disorders with learning difficulties/mental retardation

Answer 27

• Most common: Down syndrome
• 2nd common: Fragile X syndrome

Question 28

Genetic disorders with hypotonia

Answer 28

• Down syndrome
• Fragile X syndrome

Question 29

Genetic disorders with mitral valve prolapse (late systolic murmur)

Answer 29

• Marfan syndrome
• Fragile X syndrome

Question 30

Ear /Auricle change in Down syndrome and Fragile X syndrome

Answer 30

Down syndrome: small ears

Fragile X: large ears

Question 31

Testes in Fragile X and Klinefelter syndrome

Answer 31

Fragile X: Large testes

Klinefelter syndrome: Small testes