Constitutional (familial, hereditary) mastocytosis is transmitted, at least in some cases, as an autosomal dominant disorder (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20). It is characterized by occurrence in multiple generations, onset in neonatal life, and limitation of disease to the skin. A familial etiology accounts for about 10% of mastocytosis cases presenting in childhood. The skin pathology includes urticaria pigmentosa, telangiectasia macularis eruptiva perstans, and grossly normal skin with microscopic dermal mast cell hyperplasia. Constitutional mastocytosis is typically indolent and may regress spontaneously.

Other findings reported with constitutional mastocytosis include familial hyperbetalipoproteinemia, gastrointestinal stromal tumors (GIST), germ cell tumors, neurosensory deafness, and trisomy 21 (Down syndrome). Mast cells, gastrointestinal stromal cells, and germ cells express KIT, located on chromosome 4q11-q12, which encodes a tyrosine kinase that is the receptor for mast cell growth factor. Like clonal mastocytosis, GIST and germ cell tumors are associated with activating mutations of KIT.

The peripheral blood and bone marrow show no pathologic findings.

Genetic studies show a germline activating KIT mutation in some cases; others show no KIT mutations.

The differential diagnosis includes sporadic mastocytosis presenting in childhood, which does not usually show a KIT mutation, and systemic mastocytosis presenting in childhood, which typically shows an acquired activating KIT mutation (21, 22, 23). Analysis of KIT may be required to make an accurate diagnosis in an individual case.

In early published accounts of familial mast cell disease, it is difficult to determine whether the disorder is truly constitutional, possibly with a germline KIT mutation, or the occurrence of multigenerational systemic mastocytosis, which typically shows an activating KIT mutation acquired in utero or later in life.