Achondroplasia

Question 1

What is achondroplasia?

Answer 1

It is a type of skeletal dysplasia and is the most common cause of disproportionate short stature

Question 2

What gene mutation is associated with achondroplasia?

What are the consequences of this mutation?

Answer 2

FGFR3 on chromosome 4

Leads to abnormal function of epiphyseal plates= inhibits chondrocyte proliferation
I.e. restricrs bone growth in length-> short stature

Question 3

What is the inheritance pattern?

What is signficant about homozygous gene mutations

Answer 3

Autosomal dominant
Homozygous= fatal in neonatal period
Therefore anyone with achondroplasia is heterozygous

Question 4

What are the common features someone with achondroplasia might present with?

Answer 4

Disproportionate short stature i.e. around 4ft

Proximal bone (humerus and femur) affected more than other bones

Normal trunk length due to spine length not being as affected

Short digits

Bow legs (genu varum)

Disproportionate skull

Foramen magnum stenosis

Question 5

Why do individuals with achondroplasia develop a disproportionate skull?

Answer 5

Due to different areas of the skull growing by different methods

Skull base= endochondrial ossification

• affected by achondroplasia
• leads to flattened mid-face and nasal bridge and foramen magnum stenosis

Cranial vault= membranous ossification

• not affected by achondroplasia
• normal sized vault and leads to prominent forehead (frontal bossing)

Question 6

What other conditions are associated with achondroplasia?

Answer 6

Recurrent otitis media-> due to cranial abnormalities

Kyphoscoliosis

Spinal stenosis

OSA

Obesity

Cervical cord compression and hydrocephalus (due to foramen magnum stenosis)