Msk 3 Flashcards
What mutation causes achondroplasia? On what chromosome?
FGFR3; 4p16.3
What mutation causes thanatophoric dysplasia?
Gain of function in FGR3 gene
The mutation of what gene causes Thanatophoric Dysplasia type II?
K650E
What type of osteogenesis imperfecta is lethal?
Type II
In achdonroplasia, are there associated changes in lifespan, intelligence, or reproductive status?
No.
AR, b-galactosidase deficiency Accumulation of keratan sulfate & chondroitin-6-sulfate
MPS IV B
Severe shortening of limbs, extra skin folds, small chest cavity, hypoplastic lungs, respiratory insufficiency, bell-shaped abdomen
thanatophoric dysplasia
AR, deficiency in b-glucuronidase (GUSB) Accumulation of heparan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate
MPS type VII: Sly syndrome
What do the mutations of CA2 (carbonic anhydrase) and CLCN7 (chloride channel 7) cause?
interference with process of acidification of the osteoclast resorption pit, required for dissolution of ca-hydorxyapatite
Why would osteopetrosis lead to anemia with subsequent extramedullary hematopoiesis in the spleen and liver (thus causing hepatosplenomegaly)?
Bone marrow gets clogged with bone? (Tegrity)
Type I thanatophoric dysplasia is characterized by
bowed, long bones
long extremities, tall, tapering fingers & toes, kyphosis, scoliosis, chest deformity (pectus excavatum or carinatum), cardiovascular lesions
marfan syndrome
MPS’s are deficiencies of an enzyme involved in the degradation of
glycosaminoglycans (GAGs)
How many types of osteogenesis imperfecta are there?
- Know them. 3.21!
Short stature, skeletal deformities as result of hyaline cartilage, hepatosplenomegaly, valvular lesions & subendothelial arterial deposits
MPSs
Which type of osteopetrosis is malignant?
Autosomal recessive form in utero or at birth 1:20,000/ AD is benign adolescence or adult 1:250,000
Affected children appear normal at birth, year 1 develop course facial features, wide nasal bridge, flattened midface, HSM, hernias, dysotosis multiplex, corneal clouding
MPS type I: Hurler syndrome
What mutation causes marfan syndrome?
Fibrillin-1 (FBN1) - 70-80% AD, mutations in FBN2 less common and give rise to congenital contractural arachnodactyly
Type II thanatophoric dysplasia is characterized by
straight, long bones and cloverleaf skull
Does achondroplasia affect the head? Why?
No. The axial skeleton remains relatively unaffected.
What is the most lethal form of skeletal dysplasia?
Thanatophoric dysplasia 1:20,000 live births
Disease of type I collagen
Osteogenesis imperfecta (aka brittle bone disease)
AR, deficiency in a-L iduronidase (IDUA) Accumulation of heparin sulfate and dermatan sulfate
Severe form of MPS - type I: Hurler syndrome
Lysosomal storage diseases, defined by a deficiency in a lysosomal enzyme, leads to accumulations within lysosomes.
Mucopolysaccharidoses (MPS)
