Osteopetrosis associated with PLEKHM1 and SNX10 genes, both involved in osteoclast vesicular trafficking

The clinical and radiological variability seen in different forms of osteopetrosis, all due to impaired osteoclastic bone resorption, reflect many causal genes. Both defective differentiation of osteoclasts from hematopoietic stem cells as well as disturbed functioning of osteoclasts can be the underlying pathogenic mechanism. Pathogenic variants in PLEKHM1 and SNX10 can be classified among the latter as they impair vesicular transport within the osteoclast and therefore result in the absence of a ruffled border. Some of the typical radiological hallmarks of osteopetrosis can be seen, and most cases present as a relatively mild form segregating in an autosomal recessive mode of inheritance.