Skeletal Disorders

Question 1

What does the prefix rhizo- mean?

Answer 1

from the root

-melia = relating to a limb

Question 2

What does the prefix meso- mean?

Answer 2

in the middle

in the middle of the rhizo (root) and acro (tip)

-melia = relating to a limb

Question 3

What does the prefix acro- mean?

Answer 3

tip

-melia = relating to a limb

Question 4

What gene is associated with Achondroplasia and what is its inheritance pattern?

What percentage of cases are de novo?

Answer 4

FGFR3
Autosomal Dominant
80 % de novo
homozygous lethal

All of the FGFR3 conditions are Autosomal Dominant

Question 5

What is the most common cause of disproportiante small stature?

Answer 5

Achondroplasia

most people are a little over 4ft tall

Question 6

What are some key features of Achondroplasia?

Answer 6

• rhizomeric limb shortening
• bowing of legs
• kyphosis

Question 7

How can Achondroplasia effect speech development?

Answer 7

Middle ear dysfunction (>50%) –> conductive
hearing loss (40%) –> speech delay

Question 8

Which gene causes Hypochondroplasia?
What is the inheritance pattern?

Answer 8

FGFR3
Autosomal Dominant

different variants in FGFR3 than in Achondroplasia

Question 9

Key features of Hypochondroplasia.

Answer 9

• Similar to achondroplasia, but radiographic features more mild
• Children typically present with toddlers / early school age – features become more prominent over time (may not be immediately apparent at birth)
• Disproportionate short stature (rhizomelic or mesomelic) with stocky build

Question 10

Key features of
Thanatophoric Dysplasia

Answer 10

• nearly always perinatal lethal
• types 1: “telephone” shaped bowed femurs
• type 2: cloverleaf craniosynostosis

Craniosynostosis - bones in a baby’s skull join together too early

Question 11

Genetic cause of Thanatophoric Dysplasia and inheritance pattern

Answer 11

FGFR3
Autosomal Dominant

All of the FGFR3 conditions are Autosomal Dominant

Question 12

What is one condition that is caused by FGFR3 but is not a skeletal disorder?

Answer 12

Muenke Syndrome
craniosynostosis, brachydactyly (short digits), bilateral hearing loss

Question 13

Common features of Ostegenesis Imperfecta.

Answer 13

1. Fractures with minimal / absent
   trauma (extremities most common)
2. Variable dentinogenesis imperfecta (DI) – grey /brown teeth, transluscent, wear down / break
3. Hearing loss (adult, middle ear fractures)

Question 14

Describe type 1 Osteogenesis Imperfecta

Answer 14

Classic non-deforming OI with blue
sclerae

Question 15

What are the genetic causes of Osteogenesis Imperfecta?
What is the inheritance pattern?

Answer 15

COL1A1, COL1A2
Autosomal Dominant

colts break their legs and are bred for dominance