PURPOSE OF REVIEW: We give an update on the etiology and potential treatment 
options of rare inherited monogenic disorders associated with arterial 
calcification and calcific cardiac valve disease.
RECENT FINDINGS: Genetic studies of rare inherited syndromes have identified key 
regulators of ectopic calcification. Based on the pathogenic principles causing 
the diseases, these can be classified into three groups: (1) disorders of an 
increased extracellular inorganic phosphate/inorganic pyrophosphate ratio 
(generalized arterial calcification of infancy, pseudoxanthoma elasticum, 
arterial calcification and distal joint calcification, progeria, idiopathic 
basal ganglia calcification, and hyperphosphatemic familial tumoral calcinosis; 
(2) interferonopathies (Singleton-Merten syndrome); and (3) others, including 
Keutel syndrome and Gaucher disease type IIIC. Although some of the identified 
causative mechanisms are not easy to target for treatment, it has become clear 
that a disturbed serum phosphate/pyrophosphate ratio is a major force triggering 
arterial and cardiac valve calcification. Further studies will focus on 
targeting the phosphate/pyrophosphate ratio to effectively prevent and treat 
these calcific disease phenotypes.