Jacobsen syndrome hematological comorbidities

Jacobsen syndrome and hematological comorbidities – cytopenia of varying severities and morphological abnormalities in peripheral blood and bone marrow.

Jacobsen syndrome is a genetic disorder caused by deletions of the distal segment of chromosome 11q. It manifests in a variety of physical malformations and hematological comorbidities, mainly thrombocytopenia, where individuals have a low number of platelets in their blood. To expand upon the phenotype, Yamashita et al. report on four patients diagnosed with Jacobsen syndrome in a Japanese cohort of pediatric patients with bone marrow failure. The 1^st patient is a 10-year-old girl born with pulmonary hypertension and a ventricular septal defect, and later was diagnosed with anemia and thrombocytopenia. The 2^nd patient is a 15-year-old girl who did not have any prominent signs of cytopenia at birth, but recent routine medical examination revealed anemia and thrombocytopenia. The 3^rd patient had a thrombocytopenia, neutropenia, anemia, and cardiac complications. The 4^th patient had complex heart malformations, a horseshoe kidney, and thrombocytopenia. In all four patients they observed giant platelets in the peripheral blood which could be common hematological phenotype in Jacobsen syndrome. Deletions in the cohort ranged from 10.0-15.5 Mb with the 4^th patient having the largest deletion. In their literature search, the authors identified 31 additional patients with Jacobsen syndrome with hematological abnormalities such as thrombocytopenia (22/31), pancytopenia (8/31), and bicytopenia (1/31). It is suggested that haploinsufficiency of FLI1 gene, located at 11q24.3, plays a crucial role in thrombocytopenia in Jacobsen syndrome—the gene was encompassed in the deleted region in all four patients in the current cohort. Multilineage cytopenia may be a recurrent symptom of Jacobsen syndrome and identify specific blood cell morphologic abnormalities associated with the condition. However, the authors address that their study is limited in size and that further larger longitudinal studies are needed to elucidate the full picture of multilineage cytopenia.

Yamashita et al. “Hematological abnormalities in Jacobsen syndrome: cytopenia of varying severities and morphological abnormalities in peripheral blood and bone marrow”. “Haematologica,” 2023, v.108 (12), 3438-3443.

Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. For more information on any article please contact info@chromodisorder.org