Chapter 129 - Skeletal Dysplasias and Mucopolysaccharidoses

Question 1

genetic inheritance of achondroplsia?

Answer 1

autosomal dominant but 90% are new mutations

Question 2

phenotypic features of achondroplasia

Answer 2

• rhizomelic limb shortening
• abnormal facies

Question 3

pathophysiology of achondroplasia

Answer 3

FGFR-3 receptor mutation
point mutation - substitutes glycine to argenine

-> PROLIFERATIVE ZONE growth retardation

Question 4

what feature of achondroplasia resolves with motor development progression

Answer 4

thoracic kyphosis -> do no operate

Question 5

phenotypic facial features of achondroplasia

Answer 5

frontal bossing
button nose
trident hands (cant put the ring and long fingers together)
champagne glass pelvis
short thick pedicles, decreased interpedicular distance and hyperlordosis
posterior radial head dislocation

Question 6

most dangerous feature of achondroplasia

Answer 6

foramen magnum stenosis -> central apnea

Question 7

genetic inheritance of Pseudoachondroplasia

Answer 7

autosomal dominant

Question 8

genetic mutation in pseudoachondroplasia

Answer 8

mutation in COMP - cartilage oligomeric matrix protein

Chromosome 19

Question 9

Phenotypic features of pseudoachondroplasia

Answer 9

metaphyseal flaring
early onset OA and flexion contractures
NORMAL FACIES
normal development until age 2
DDH
Scoli with platyspondyly (flattened vertebrae)

Question 10

most dangerous feature of Pseudoachondroplasia

Answer 10

Odontoid hypoplasia -> C1-2 instabillity

Question 11

genetic inheritance for diastrophic dysplsia

Answer 11

autosomal RECESSIVE

Question 12

genetic defect in diastrophic dysplasia

Answer 12

sulfate transport protein mutation -> cartilage matrix defect
FINNISH descent

Question 13

phenotype for diastrophic dysplasia

Answer 13

hitchhiker’s thumb
cauliflower ear
cleft palate

Also:
cervical kyphosis
flexion contractures (including dislocated patellae)
rigid clubfeet

Question 14

genetic inheritance pattern for cleidocranial dysostosis

Answer 14

autosomal DOMINANT

Question 15

genetic defect - cleidocranial dysostosis

Answer 15

Core-binding factor alpha-1 (CBFA-1) -> transcription factor for osteocalcin

-> affects INTRAMEMBRANOUS ossification

Question 16

phenotype for cleidocranial dysostosis

Answer 16

delayed skull suture closing
- frontal bossing
- delayed permanent teeth eruption
- aplasia of clavicles - can bring shoulders to touch anteriorly
- widened pubic symphysis
- coxa vara
shortening of the middle phalanges of the 3rd -5th fingers

Question 17

genetic inheritance for muchopolysaccharidoses

Answer 17

ALL are autosomal RECESSIVE

EXCEPT Hunter Syndrome - X-Linked recessive

• think hunters = mark the spot with an x, or see an x in their gunsight

Question 18

if you get a patient with muschopolysaccharidosis what condition should you be thinking of?

Answer 18

cervical instability - get C1-C2 fusion

Question 19

genetic inheritance for multiple epiphyseal dysplasia

Answer 19

Autosomal DOMINANT

Question 20

genetic defect in multiple epiphyseal dysplasia

Answer 20

COMP (cartilage ologomeric matrix protein) mutation and COL9A2 mutation - a linker protein for type II collagen

Question 21

phenotype for multiple epiphyseal dysplasia

Answer 21

IF YOU SEE A BILATERAL PERTHES, IT IS MED UNTIL PROVEN OTHERWISE

proportionate dwarfism
often not noticed until mid-childhood - early development is normal
- multiple abnormal epiphyses
- shortened metacarpals and metatarsals
- valgus knees, double layer patella

NO SPINAL INVOLVEMENT

Question 22

genetic inheritance of spondyloepiphyseal dysplasia

Answer 22

most common: Autosomal dominant (apparent at birth)

much more rare: x-linked recessive (doesnt appear for 8-10 years)

Question 23

genetic mutations involved in spondyloepiphyseal dysplasia

Answer 23

common, AD form: Col2A1 - encodes type II collagen, affects PROLIFERATIVE ZONE chondrocytes

rare XR form (SED tarda): SEDL gene

Question 24

phenotypes for spondyloepiphyseal dysplasia

Answer 24

BOTH: cervical instability, extremely short stature, platyspondyly, delayed epiphyseal ossification

Congenita:
coxa vara
genu valgum
planovalgus feet
retinal detachment
mypoia
hearing loss

Tarda: dislocated hips, genu valgum not as often

Question 25

Nail patella syndrome

Answer 25

• dislocated radial head
• glaucoma
• 1/3 of adults develop renal failure and glaucoma