Genetic transmission of tumoral calcinosis: autosomal dominant with variable clinical expressivity

Tumoral calcinosis is a rare inherited metabolic disorder characterized by hyperphosphatemia, elevated serum 1,25-dihydroxyvitamin D levels and periarticular cystic and solid calcifications. Based on previous investigations, the inheritance of this disorder has been postulated to be autosomal recessive. This interpretation was based on finding clinically affected subjects in only single generations of kindreds. We investigated four generations of an affected kindred and found nine subjects with the disease. A unique dental lesion which is specific for this disorder and serves as a phenotypic marker was identified in two generations of the kindred. In all affected subjects, elevated serum 1,25-dihydroxyvitamin D levels were found, although each member did not have the classical clinical findings of tumoral calcinosis. The possibility that this disorder may be variably expressed and have multiple formes frustes has not been previously considered. Using the unique dental lesion as well as the classical clinical and biochemical abnormalities, we found that in this kindred, tumoral calcinosis is transmitted in an autosomal dominant mode, with variable clinical expressivity.