Rambam–Hasharon syndrome of psychomotor retardation, short stature, defective neutrophil motility, and bombay phenotype

TLDR

The syndrome’s appearance in two unrelated families indicates that its diverse features likely stem from a single underlying mutation. Homozygosity‑by‑descent for a deletion of contiguous genes, or a mutation affecting the ubiquitous GDP‑fucose donor, may account for the syndrome’s pleiotropic manifestations. Two Arab patients exhibited severe mental retardation, microcephaly, cortical atrophy, seizures, hypotonia, dwarfism, recurrent infections with neutrophilia, markedly reduced neutrophil motility but normal opsonophagocytic activity, and both displayed the Bombay (hh) phenotype, while familial endocardial fibroelastosis and tetralogy of Fallot segregated independently. © Wiley‑Liss, Inc.

Abstract

Abstract We describe 2 Arab patients, both offspring of unrelated consanguineous matings, with unusual facial appearance, severe mental retardation, microcephaly, cortical atrophy, seizures, hypotonia, dwarfism, and recurrent infections with neutrophilia. Neutrophil motility was markedly decreased but the opsonophagocytic activity was normal. Both patients lack the red blood cell (RBC) H antigen and manifest the Bombay (hh) phenotype. Familial endocardial fibroelastosis and familial tetralogy of Fallot segregated independently in one family. The occurrence of the same syndrome in 2 unrelated families suggests that the various aspects of the disorder are the pleiotropic effects of a single mutation. Homozygosity‐by‐descent for a deletion involving contiguous genes may explain the findings in this syndrome. Alternatively, a mutation which involves an ubiquitous GDP fucose donor rather than the enzyme (α 2 ‐ L ‐fucosyltransferase) or its substrate (glcNAc) may account for the pleiotropic manifestations in this syndrome. © Wiley‐Liss, Inc.