Flashcards in Case Studies Deck (40)
Rhizomelic short stature
Spinal cord compression
Brainstem compression (10%)
Achodroplasia risk of death?
Between 3-7% of patients die unexpectedly in first year because of brainstem compression (central apnea) or obstructive apnea
Mutation in FGFR3
FGFR3 (fibroblast growth factor receptor 3)
Two mutations (both converting Gly380Arg) account for 99%
Type of mutation?
Gain of function
Cause ligand independent activation of FGFR3 (a transmembrane tyrosine kinase receptor)
What happens in achondroplasia when FGFR3 is independently on?
Inappropriately inhibits bony growth
Achondroplasia due to de novo mutation in whose germline?
And increase with age
Mutations in FGFR gene frequently lead to?
Issues with boney growth and bone fusion
FGFR3 Gly380Arg -->
Gain of function leading to achondroplasia
Congenital deafness (From birth) is usually ?
Progressive childhood deafness is usually?
Of genetic congenital deafness, what fraction is syndromic and what fraction is nonsyndromic (meaning there is no other issue)
Which mutation accounts for 1/2 of all nonsyndromic autosomal recessive deafness?
GJB2 implicated in ?
1/2 all recessive nonsyndromic deafness
retinitis pigmentosa suggests
Usher (AR) syndrome
Thyroid goiter suggests?
Pendred (#2 AR) syndrome
sudden death suggests
Jurvell and Lange-Nielson (AR) syndrome
white forelock suggests?
Waardenburg (#1 AD) syndrome
8th nerve schwannomas suggests?
NF type II
What percent of congenital deafness is genetic?
What percent of genetic congenital deafness is nonsyndromic?
Of nonsyndromic congenital genetic deafness, what percent is autosomal recessive?
Of autosomal recessive congential nonsyndromic deafness, which gene is reponsible for 1/2
Severe congenital deafness is typically due to?
nonsyndromic progressive deafness with childhood onset is typically due to?
To calculate risk from pedigree, must be certain you are not dealing with genetic heterogeneity, e.g. the risk of two deaf people (homozygous recessive for their deaf gene) to have a deaf child is?
Because you don't know if their same gene is effected?
Most common category of congenital deafness?
Genetic, autosomal recessive, nonsyndromic due to GJB2
Fragile X syndrome
Fragile X syndrome
What is the cause?
Full triple repeat expansion