Diagnostic criteria
- At least 2 of these features need to be present to diagnose the condition
- Endocrine abnormalities
- Precocious puberty (in females)
- Unilateral café au lait spots with jagged edges
- Fibrous dysplasia
- Development of abnormal fibrous tissue instead of bone
- Can lead to
- Osteosarcoma (2% of patients with MAS)
- Bony changes in the skull can result in damage to nerves causing vision and/or hearing loss.
- Bony changes in the chest wall may lead to difficulty breathing.
Genetic
- Spontaneous (chance) mutation in the GNAS1 gene
- This gene then forms an abnormal protein that regulates cell proliferation, migration and survival.
- Mosaicism
- The hormones MSH (melanocyte stimulating hormone), LH (luteinizing hormone), TSH (thyroid stimulating hormone), GHRH (growth hormone stimulating hormone), and ACTH (adrenocrotical stimulating hormone) all signal through the G protein (alpha, beta, gamma subunits) pathway.
- In MAS, the alpha subunit is mutated in such a way as to induce constitutive activation of adenylate cyclase, and thus produce high levels of intracellular cAMP.
- This results in increased production of melanin, estradiol (E2), testosterone (T), thyroxine (T4), growth hormone (GH), and cortisol.
- Dysregulated production of these hormones results in café-au-lait spots, precocious puberty, fibrous dysplasia, acromegaly, hyperthyroidism, and Cushing's disease, depending on the tissue harboring the somatic mutation.
- G-protein mutation: GNAS1 mutations
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