Chapter 129 - Skeletal Dysplasias and Mucopolysaccharidoses Flashcards
genetic inheritance of achondroplsia?
autosomal dominant but 90% are new mutations
phenotypic features of achondroplasia
- rhizomelic limb shortening
- abnormal facies
pathophysiology of achondroplasia
FGFR-3 receptor mutation
point mutation - substitutes glycine to argenine
-> PROLIFERATIVE ZONE growth retardation
what feature of achondroplasia resolves with motor development progression
thoracic kyphosis -> do no operate
phenotypic facial features of achondroplasia
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
most dangerous feature of achondroplasia
foramen magnum stenosis -> central apnea
genetic inheritance of Pseudoachondroplasia
autosomal dominant
genetic mutation in pseudoachondroplasia
mutation in COMP - cartilage oligomeric matrix protein
Chromosome 19
Phenotypic features of pseudoachondroplasia
metaphyseal flaring
early onset OA and flexion contractures
NORMAL FACIES
normal development until age 2
DDH
Scoli with platyspondyly (flattened vertebrae)
most dangerous feature of Pseudoachondroplasia
Odontoid hypoplasia -> C1-2 instabillity
genetic inheritance for diastrophic dysplsia
autosomal RECESSIVE
genetic defect in diastrophic dysplasia
sulfate transport protein mutation -> cartilage matrix defect
FINNISH descent
phenotype for diastrophic dysplasia
hitchhiker’s thumb
cauliflower ear
cleft palate
Also:
cervical kyphosis
flexion contractures (including dislocated patellae)
rigid clubfeet
genetic inheritance pattern for cleidocranial dysostosis
autosomal DOMINANT
genetic defect - cleidocranial dysostosis
Core-binding factor alpha-1 (CBFA-1) -> transcription factor for osteocalcin
-> affects INTRAMEMBRANOUS ossification
phenotype for cleidocranial dysostosis
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
genetic inheritance for muchopolysaccharidoses
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
if you get a patient with muschopolysaccharidosis what condition should you be thinking of?
cervical instability - get C1-C2 fusion
genetic inheritance for multiple epiphyseal dysplasia
Autosomal DOMINANT
genetic defect in multiple epiphyseal dysplasia
COMP (cartilage ologomeric matrix protein) mutation and COL9A2 mutation - a linker protein for type II collagen
phenotype for multiple epiphyseal dysplasia
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
genetic inheritance of spondyloepiphyseal dysplasia
most common: Autosomal dominant (apparent at birth)
much more rare: x-linked recessive (doesnt appear for 8-10 years)
genetic mutations involved in spondyloepiphyseal dysplasia
common, AD form: Col2A1 - encodes type II collagen, affects PROLIFERATIVE ZONE chondrocytes
rare XR form (SED tarda): SEDL gene
phenotypes for spondyloepiphyseal dysplasia
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
Nail patella syndrome
- dislocated radial head
- glaucoma
- 1/3 of adults develop renal failure and glaucoma
