Systemic mast cell activation disease variants and certain genetically determined comorbidities may be consequences of a common underlying disease

The available research data about mast cell activation disease (MCAD, a common disease with prevalence estimated at 17???20%) suggest it may be rooted in an unnamed transgenerationally transmittable epigenetic disease. As a result, somatic and germline mutations in a variety of genes occur which finally manifest in MCAD and its comorbidities. The combinatorial calculated number of possible combinations of such genetic alterations in mast cells results in a unique mutational pattern or profile in each patient, inducing a unique pattern of aberrant mast cell mediator production and release. Therefore, treatment must be guided by the individual???s clinical symptoms. The number of generations which the unnamed underlying epigenetic disease will affect by transgenerational transmission cannot be predicted because of insufficient knowledge about the causative processes driving this transgenerational epigenetic disease. However, in contrast to genetic diseases, epigenetic diseases are, in principle, reversible, such that individual MCAD might be able to be induced into remission, perhaps even cured, by drugs targeting the epigenome. However, new epigenomic drugs with much better risk???benefit ratios than existing epigenomic drugs are needed. Since there is currently at best only a vague conception of the processes driving transgenerational transmission, cessation and, thus, remission or cure of the epigenetic disease likely will not be inducible by drugs in the near future. The presented novel concept of MCAD being rooted in an unnamed epigenetic disease has impact on research, diagnosis and treatment of MCAD.