Achondroplasia, Hypochondroplasia and Tanatophor Dysplasia

Question 0

Genetic defect

Answer 0

Point mutation in FGFR3 (4p) 1138

Arg-> Gly

Question 1

Important facts

Answer 1

Achondroplasia: transmembrane domain
Hypochondroplasia: tyrosine kinase domain
Tanatophor dysplasia: tyrosine kinase domain

Question 2

Gene mechanism and fuction

Answer 2

Gene is expressed in physis(bone) and CNS
Normal fucntion is inhibit the proliferation of chondrocyte in proliferation zone of physis, help to regulate bone growth by inhibiting the endochrondral ossification

Question 3

Gene mutation effects

Answer 3

FGFR 3 deficiency > growth faster longer period
The receptor is active even without FGF 3 binding-> superly inhibit the growth and ossification-> short statue
-> GAIN FUCNTION MUTATION

Question 4

Differential diagnosis

Answer 4

Cartilage hair hynoplasia
Campomelic dysplasia
Pseudchondroplasia

Question 5

Cartilage hair dysplasia

Answer 5

Short statue
Gene varum
Curvature of femur
Thin, fragile hair
Irregular, enlarge metaphase
Immunodeficiency

Question 6

Campomelic dysplasia

Answer 6

AD/AR: 17q24,3-24,1
Curvature of lower 1/3 of tibia
Thickening of corticalis
Hypoplasia of fibula
Curvature of femur
Pes equinovarus
Opposite gender (XY-female phenotype)

Question 7

Pseudochondroplasia

Answer 7

AD/AR- gene in pericentric region of chromosome 9
One of the most common skeletal dysplasia with manifestation 1-3 years
Along with growth it become more expressed