Markedly elevated bone mineral density in genetically elusive familial hypocalciuric hypercalcemia: A case report with targeted genetic analysis of eight candidate genes

We report an 88-year-old Japanese woman with markedly elevated bone mineral density (lumbar spine 212% of young adult mean, Z–score + 10.0 SD) diagnosed with familial hypocalciuric hypercalcemia based on a urinary calcium-to-creatinine ratio of 0.06. Tergeted genetic testing of eight genes revealed no pathogenic variants; a CASR variant (c.1733-9A>G) was a common Japanese polymorphism (frequency 1/808). This genetically elusive case highlights the extreme skeletal phenotype in FHH and the essential role of population-specific databases in variant interpretation. ©The Authors. All rights reserved. • An 88-year-old FHH patient exhibited lumbar spine BMD of 212% (Z-score + 10.0 SD). • Targeted genetic analysis of eight genes identified no pathogenic variants. • The CASR c.1733-9A>G variant was confirmed benign in Japanese databases. • Extreme BMD likely reflects cumulative PTH anabolic effects over decades. • Population-specific databases are crucial for accurate FHH variant interpretation.