McCune-Albright Syndrome as a Rare Cause of Fanconi Syndrome and Kidney Failure: A Case Report and Literature Review

McCune-Albright syndrome (MAS) is a rare systemic genetic condition classically characterized by childhood-onset polyostotic fibrous dysplasia, café-au-lait skin pigmentation, and precocious puberty. Kidney involvement in MAS is infrequently recognized, particularly in low- and middle-income countries where genomic testing may be limited. We presented the first case report of MAS presenting with Fanconi syndrome and progressive kidney failure, which we postulated represents a phenotypic expansion of the renal phenotype associated with MAS, in addition to hyperthyroidism, osteoid osteoma, bone marrow failure secondary to fibrous dysplasia, and congenital ovarian failure. Initial renal biochemical evaluations were suggestive of proximal tubulopathy; however, secondary investigations were inconclusive. Seventeen years after the patient's initial presentation, clinically accredited whole exome sequencing conducted under a national genomic research initiative identified a pathogenic GNAS variant (NM_000516:c.[602G>A];p.(Arg201His)), confirming a diagnosis of MAS. This is the first reported case of GNAS-associated Fanconi syndrome and kidney failure. We hypothesized that dysfunction of proximal tubule transporters may be related to elevated circulating cyclic adenosine monophosphate levels and selective expression of G protein-coupled receptors in the proximal tubule, mediated by a gain-of-function in the G-protein α subunit induced by the GNAS pathogenic variant.