Hereditary splenomegaly with hypersplenism

Abstract

We report seven children with a clinically benign form of primary splenomegaly associated with hematologic evidence of hypersplenism. Five belong to one sibship, the other two are second cousins of each other and of the group of siblings. Splenectomy was performed in five subjects, but pedigree evidence of this autosomal dominant trait tends to indicate that complete clinical resolution occurs normally so that transmitting adults show no splenomegaly or hypersplenism. This appears to be a newly recognized Mende‐lian mutation which is evident (“penetrant”) only in childhood, and which may possibly have pleiotropic effects on eye and CNS development.

Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop

“…1,2 The clinical antecedents to ALPS entail various syndromes of familial chronic nonmalignant lymphadenopathy and splenomegaly, including pseudomononucleosis, pseudolymphoma, and the Canale-Smith syndrome. [3][4][5] In 1992, Sneller et al 6 recognized that these entities resembled 2 related mouse strains with lymphoproliferative phenotypes known as lpr (lymphoproliferation) and gld (generalized lymphoproliferative disease). Earlier that same year the molecular defect of the lpr mouse was shown to be a loss of function mutation in a "death receptor" gene that is a member of the tumor necrosis factor receptor superfamily, FAS/CD95/APO-1/TNFRSF6.…”