Other Genetic Syndromes

Question 1

What is achondroplasia?

Answer 1

It is a form of short limb dwarfism which is caused by mutations in the FGFR3 gene.

Inheritance is autosomal dominant. Although many cases are due to de novo mutations in the FGFR3 gene.

Question 2

What is the clinical presentation of those with achondroplasia?

Answer 2

Short stature with short limb length.
Macrocephaly.

Normal intelligence and life expectancy.

More prone to developing spinal abnormalities:

• Lordiosis
• Kyphosis
• Spinal stenosis

Question 3

What is Noonan’s syndrome?

Answer 3

It is an autosomal dominant disorder characterised by:

• dysmorphic features including short stature
• congenital cardiac defect
• bleeding (repeated nosebleeds/menorrhagia)
• chest wall deformities
• undescended testicles

Question 4

What are the dysmorphic features of Noonan’s?

Answer 4

General:
Short stature

Face:
Low hair line
Wide spaced eyes
Low set ears
Small jaw

Other:
Webbed neck
Chest wall deformities

Question 5

What is Fragile X syndrome?

Answer 5

It is an X linked dominant condition (therefore women with one affected gene will be affected).

Which is characterised by dysmorphic features, learning difficulties and developmental delay.

Men have a more severe phenotypic presentation.

Question 6

What is Marfan’s syndrome and what are the clinical features?

Answer 6

It is an autosomal dominant connective tissue disorder. However (25% have de novo mutations)

It is characterised by:
Tall stature
Arm span greater than height
Hyper-flexibility

The main clinical features are:

• Ectopia lentis (dislocated lenses in the eyes)
• Aortic aneurysm/dissections
• Chest wall deformities

Question 7

What is phenylketonuria (PKU)?

Answer 7

It is an autosomal recessive disease in which there are high levels of phenylalanine in the blood.

If not treated this can cause:

• developmental delay
• learning difficulties
• seizures

It is a spectrum of disorders ranging from severe classical PKU and mild diseases.

Phenylalanine can also act as a teratogen so women with PKU often have babies with learning difficulties.

Question 8

What is Rett’s syndrome?

Answer 8

It is a de novo genetic disorder which occurs in females.

It is characterised by normal development unto 6-18months of age followed by developmental regression in language and motor domains.

Question 9

What is Prader-Willi syndrome?

Answer 9

It is a genetic disorder caused by a deletion on the long arm of the paternal chromosome 15.

It is characterised by:

• Underdeveloped genitalia causing infertility
• Unsatiable appetite leading to obesity
• Learning difficulties
• Behavioural problems such as temper tantrums

Question 10

What is Angelman’s syndrome?

Answer 10

It is a genetic disorder caused by a deletion on the long arm of the maternal chromosome 15.

It is characterised by:

• delayed development
• learning difficulties
• severe speech impairment
• ataxia
• microcephaly
• seizures

Those with angle mans often have a happy excitable demeanour.

Question 11

What is Williams syndrome?

Answer 11

It is a genetic disorder which usually occurs due de novo mutations.

It is characterised by:

• mild to moderate intellectual disability
• friendly personality characteristics
• dysmorphic features
• cardiac defects (supravalvular aortic stenosis)