What is the characteristic triad of features in McCune-Albright Syndrome?
Polyostotic fibrous dysplasia
Cafe-au-lait skin pigmentation
Autonomous endocrine hyperfunction
What does the gene involved in McCune-Albright syndrome encode for?
Alpha subunit of a G-protein
What is the proposed mechanism for the phenotype resulting from the mutation of the G protein in McCune-Albright syndrome?
Mutation in G protein --> inactivation of intrinsic GTPase activity --> prevents inactivation of Gs alpha subunit once activated --> continuous stimulation of AC even in absence of ligand binding to receptor --> increased intracellular cAMP and continual stimulation of downstream cAMP signalling cascades
How does the pattern of inheritance of McCune-Albright syndrome result in the variable phenotype?
Post zygotic somatic mutation
-- All daughter cells of embryonic cell inwhich mutation occurs contain mutation
-- the earlier in embryogenesis that the mutation occurs the more widespread the involvement
What is the most common endocrine features of McCune-Albright syndrome?
What is the cause of precocious puberty in McCune-Albright syndrome and what are the ramifications for growth?
result of gonadotropin independent autonomous ovarian or testicular function
results in sexual precocity, increased growth velocity and advanced skeletal maturity
What are the endocrine features of McCune-Albright syndrome?
ACTH-independent Cushings syndrome (growth failure and HTN in infancy)