Adult-onset calcification of the lower extremity arteries, including the iliac, femoral, and tibial arteries, and hand and foot capsule joints is an autosomal recessive condition that represents only the second mendelian disorder of isolated calcification (see generalized arterial calcification of infancy (GACI), 208000). Age of onset has been reported as early as the second decade of life, usually involving intense joint pain or calcification in the hands (St. Hilaire et al., 2011).

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common degenerative spinal disorder that causes severe neurologic dysfunction in middle-aged and elderly populations. This ectopic ossification results in compression of the spinal cord and nerve root by the ossified ligament. Histologic studies of OPLL suggest that OPLL develops through a process of endochondral ossification (summary by Nakajima et al., 2016).

Greenberg dysplasia (GRBGD), also known as hydrops-ectopic calcification-moth-eaten (HEM) skeletal dysplasia, is a rare autosomal recessive osteochondrodysplasia characterized by gross fetal hydrops, severe shortening of all long bones with a moth-eaten radiographic appearance, platyspondyly, disorganization of chondroosseous calcification, and ectopic ossification centers. It is lethal in utero. Patient fibroblasts show increased levels of cholesta-8,14-dien-3-beta-ol, suggesting a defect of sterol metabolism (summary by Konstantinidou et al., 2008). Herman (2003) reviewed the cholesterol biosynthetic pathway and 6 disorders involving enzyme defects in postsqualene cholesterol biosynthesis: Smith-Lemli-Opitz syndrome (SLOS; 270400), desmosterolosis (602398), X-linked dominant chondrodysplasia punctata (CDPX2; 302960), CHILD syndrome (308050), lathosterolosis (607330), and HEM skeletal dysplasia.