Multicentric Carpotarsal Osteolysis
Multicentric Carpotarsal Osteolysis (MCTO) is a rare skeletal dysplasia characterized by aggressive osteolysis [resorption of bone], particularly affecting the carpal and tarsal bones, and is frequently associated with renal failure. - Zankl, A., et al. (2012). "Multicentric Carpotarsal Osteolysis Is Caused by Mutations Clustering in the Amino-Terminal Transcriptional Activation Domain of MAFB." The American Journal of Human Genetics 90: 494-501. .
Skeletal dysplasias are rare disorders that cause abnormal growth and development. This particular condition is cased by a mutation of the MAFB gene. MAFB encodes a transcription factor that plays a critical role in regulation of osteoclast differentiation (degradation of bone.)
But, we don’t know enough about how the mutation causes the phenotype (observable characteristics of an individual) of the disorder. Osteoclasts do not appear to be the ONLY CAUSE of the problem. Further, the disease appears to manifest a bit differently in each of the - possibly only 30 - identified patients in the world. We are faced with a number of conundrums. To name a few:
1) The disorder is always misdiagnosed for arthritis or chronic kidney disease. Perhaps there are people living with the disorder, that have not had whole genome or whole exome sequencing to discover the mutation. There is some variability with how the disorder manifests.
2) There is no standard course or timeline of disintegration. Each patient has a slightly different variant, manifestation and extremeness of symptoms. Known treatments for symptoms have been ruled out due to ineffectiveness.
3) The disease appears not to be ONLY osteoclast driven (because anti-resorptive medications are not effective in stopping the progressive loss of bone) even though the result is disappearance of bone cells without regeneration.
4) There is such a small number of people identified with the disease, so funding for a treatment or cure is non-existent. And red tape involving patient research and data sharing, especially across international boarders is an enormous block to progress.
We need more information beyond the surface that has been scratched, and gathering it requires funding and a team to champion the cause. Whether that be discovering something entirely new or repurposing a medication already used for a more common disease - we are determined to find it.
At just under 3 years old Sophie does not show contractures (shortening and hardening of muscles, tendons, other tissue leading to deformity and rigidity of joints) in the hands yet, although it is one of the characteristics that tends to happen in all cases. Her symptoms can be seen in X-rays. There is a marked decrease in size of the wrist compartments bilaterally. The carpal bones are small and irregular in appearance. There is a tapering of her metatarsals and an irregularity of the distal radio epiphysis. The talus and calcaneus in her feet are small and irregular, there is a decrease in the size of the mid foot compartment bilaterally. Her feet point inwards and roll out on the side, such that she does not walk with her feet pressed flat to the ground. She cannot climb stairs, she cannot hop or jump.