Heterozygous mutations in MECOM (MDS1 and EVI1 complex locus) have been reported 
to be causative of a rare association of congenital amegakaryocytic 
thrombocytopenia and radioulnar synostosis. Here we report on 12 patients with 
congenital hypomegakaryocytic thrombocytopenia caused by MECOM mutations 
(including 10 novel mutations). The mutations affected different functional 
domains of the EVI1 protein. The spectrum of phenotypes was much broader than 
initially reported for the first 3 patients; we found familial as well as 
sporadic cases, and the clinical spectrum ranged from isolated radioulnar 
synostosis with no or mild hematological involvement to severe bone marrow 
failure without obvious skeletal abnormality. The clinical picture included 
radioulnar synostosis, bone marrow failure, clinodactyly, cardiac and renal 
malformations, B-cell deficiency, and presenile hearing loss. No single clinical 
manifestation was detected in all patients affected by MECOM mutations. 
Radioulnar synostosis and B-cell deficiency were observed only in patients with 
mutations affecting a short region in the C-terminal zinc finger domain of EVI1. 
We propose the term MECOM-associated syndrome for this heterogeneous hereditary 
disease and inclusion of MECOM sequencing in the diagnostic workup of congenital 
bone marrow failure.