Which are the causes of Mandibuloacral Dysplasia?

Mandibuloacral dysplasia (MAD) is a rare genetic disorder that affects various parts of the body, including the jawbone (mandible) and the extremities (acral). It is characterized by a combination of skeletal abnormalities, skin changes, and metabolic disturbances. The exact cause of MAD is not yet fully understood, but it is believed to be primarily caused by mutations in certain genes.

LMNA Gene Mutations: The most common cause of MAD is mutations in the LMNA gene, which provides instructions for producing a protein called lamin A/C. Lamin A/C is involved in maintaining the structure and function of the cell nucleus. Mutations in the LMNA gene can disrupt the normal production or function of lamin A/C, leading to the characteristic features of MAD.

ZMPSTE24 Gene Mutations: Another gene associated with MAD is the ZMPSTE24 gene. This gene provides instructions for producing an enzyme called zinc metalloproteinase STE24. This enzyme is involved in the processing of lamin A/C, ensuring its proper function. Mutations in the ZMPSTE24 gene can impair the processing of lamin A/C, leading to the development of MAD.

Autosomal Recessive Inheritance: Mandibuloacral dysplasia is inherited in an autosomal recessive manner, which means that an affected individual must inherit two copies of the mutated gene (one from each parent) to develop the disorder. If both parents are carriers of the mutated gene, each of their children has a 25% chance of inheriting two copies and developing MAD.

Other Genetic Factors: In some cases, MAD may be caused by mutations in other genes that are not yet fully identified. Researchers are actively studying the genetic basis of MAD to uncover additional genes and mutations associated with the disorder.

Environmental Factors: While the primary cause of MAD is genetic, it is important to note that environmental factors do not play a significant role in the development of this disorder. MAD is primarily a result of inherited gene mutations rather than external influences.

Overall, the causes of Mandibuloacral Dysplasia are primarily genetic, with mutations in the LMNA and ZMPSTE24 genes being the most common known causes. Further research is needed to fully understand the genetic basis of MAD and identify additional genes involved in its development.