Albright-McCune syndrome is characterised by:
- cafe au lait spots - more precisely Coast of Maine lesions, describing the less sharp edges of the patches
- cystic bone lesions - polyostic fibrous dysplasia
- precocious puberty
- other possible findings include renal phosphate wasting and hyperfunctioning endocroninopathies e.g. acromegaly, hyperthyroidism, Cushing's syndrome
The underlying problem is with a mutation in the intracellular messanger G protein:
- in patients with this condition the underlying defect consists of post-zygotic activating mutations in the GNAS1 gene - this gene codes for the alpha subunit of the signalling G protein
- this alpha subunit causes ligand-dependent activation of cAMP signalling pathway and results in cellular hyperfunction, and in some cases hyperplasia
- affected tissues in patients with McCune-Albright syndrome have a mutation of the G3a subunit of the G3 protein that activates adenylate cyclase
- this activating mutation leads to continued stimulation of endocrine function, eg, precocious puberty
Patients with McCune-Albright syndrome are phenotypically somatic mosaics. This is because the mutation is post-zygotic.
Reference:
- (1) Lancet 2001;357 (9273): 2011.
- (2) Saenger P, Rincon M.Precocious puberty: McCune-Albright syndrome and beyond.J Pediatr. 2003 Jul;143(1):9-10.