McCune-Albright syndrome — SCE Endocrinology MCQ

Correct answer: B — Post-zygotic activating GNAS mosaicism causing McCune–Albright syndrome

The best answer is “Post-zygotic activating GNAS mosaicism causing McCune–Albright syndrome”. Fibrous dysplasia, café-au-lait pigmentation and autonomous endocrine hyperfunction form the McCune–Albright spectrum, which results from post-zygotic GNAS activation and therefore has a mosaic distribution. “A germline RET pathogenic variant causing MEN2A” is less appropriate because RET-related MEN2 causes endocrine neoplasia rather than mosaic fibrous dysplasia “Biallelic AIRE variants causing autoimmune polyglandular syndrome type 1” is less appropriate because AIRE disease causes autoimmune gland failure, chronic candidiasis and hypoparathyroidism rather than autonomous hormone excess with bone lesions “A germline MEN1 pathogenic variant” is less appropriate because MEN1 causes parathyroid, pituitary and gastro-entero-pancreatic tumours without the characteristic skin and skeletal mosaicism “A maternally inherited mitochondrial variant causing endocrine failure” is less appropriate because the phenotype reflects somatic G-protein signalling rather than maternally inherited mitochondrial disease

Reference: GeneReviews: Fibrous Dysplasia/McCune-Albright Syndrome. https://www.ncbi.nlm.nih.gov/books/NBK274564/