5q minus (5q-) syndrome is a type of bone marrow disorder called myelodysplastic syndrome (MDS). MDS comprises a group of conditions in which immature blood cells fail to develop normally, resulting in too many immature cells and too few normal mature blood cells. In 5q- syndrome, development of red blood cells is particularly affected, leading to a shortage of these cells (anemia). In addition, the red blood cells that are present are unusually large (macrocytic). Although many people with 5q- syndrome have no symptoms related to anemia, especially in the early stages of the condition, some affected individuals develop extreme tiredness (fatigue), weakness, and an abnormally pale appearance (pallor) as the condition worsens. Individuals with 5q- syndrome also have abnormal development of bone marrow cells called megakaryocytes, which produce platelets, the cells involved in blood clotting. A common finding in people with 5q- syndrome is abnormal cells described as hypolobated megakaryocytes. In addition, some individuals with 5q- syndrome have an excess of platelets, while others have normal numbers of platelets.

MDS is considered a slow-growing (chronic) blood cancer. It can progress to a fast-growing blood cancer called acute myeloid leukemia (AML). Progression to AML occurs less commonly in people with 5q- syndrome than in those with other forms of MDS.

MDS affects nearly 1 in 20,000 people in the United States. It is thought that 5q- syndrome accounts for 15 percent of MDS cases. Unlike other forms of MDS, which occur more frequently in men than women, 5q- syndrome is more than twice as common in women.

5q- syndrome is caused by deletion of a region of DNA from the long (q) arm of chromosome 5. Most people with 5q- syndrome are missing a sequence of about 1.5 million DNA building blocks (base pairs), also written as 1.5 megabases (Mb). However, the size of the deleted region varies. This deletion occurs in immature blood cells during a person's lifetime and affects one of the two copies of chromosome 5 in each cell.

The commonly deleted region of DNA contains 40 genes, many of which play a critical role in normal blood cell development. Research suggests that loss of multiple genes in this region contributes to the features of 5q- syndrome. Loss of the RPS14 gene leads to the problems with red blood cell development characteristic of 5q- syndrome, and loss of MIR145 or MIR146A contributes to the megakaryocyte and platelet abnormalities and may promote the overgrowth of immature cells. Scientists are still determining how the loss of other genes in the deleted region might be involved in the features of 5q- syndrome.

Genetic Testing Information

• Genetic Testing Registry: Myelodysplastic syndrome associated with isolated del(5q)

Genetic and Rare Diseases Information Center

• Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• CHROMOSOME 5q DELETION SYNDROME

Scientific Articles on PubMed

• PubMed

• Dutt S, Narla A, Lin K, Mullally A, Abayasekara N, Megerdichian C, Wilson FH, Currie T, Khanna-Gupta A, Berliner N, Kutok JL, Ebert BL. Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood. 2011 Mar 3;117(9):2567-76. doi: 10.1182/blood-2010-07-295238. Epub 2010 Nov 10. Citation on PubMed or Free article on PubMed Central
• Ebert BL, Pretz J, Bosco J, Chang CY, Tamayo P, Galili N, Raza A, Root DE, Attar E, Ellis SR, Golub TR. Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature. 2008 Jan 17;451(7176):335-9. doi: 10.1038/nature06494. Citation on PubMed or Free article on PubMed Central
• Gaballa MR, Besa EC. Myelodysplastic syndromes with 5q deletion: pathophysiology and role of lenalidomide. Ann Hematol. 2014 May;93(5):723-33. doi: 10.1007/s00277-014-2022-3. Epub 2014 Mar 14. Citation on PubMed
• Giagounidis A, Mufti GJ, Fenaux P, Germing U, List A, MacBeth KJ. Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes. Ann Hematol. 2014 Jan;93(1):1-11. doi: 10.1007/s00277-013-1863-5. Epub 2013 Sep 10. Citation on PubMed or Free article on PubMed Central
• Komrokji RS, Padron E, Ebert BL, List AF. Deletion 5q MDS: molecular and therapeutic implications. Best Pract Res Clin Haematol. 2013 Dec;26(4):365-75. doi: 10.1016/j.beha.2013.10.013. Epub 2013 Oct 16. Citation on PubMed
• Kumar MS, Narla A, Nonami A, Mullally A, Dimitrova N, Ball B, McAuley JR, Poveromo L, Kutok JL, Galili N, Raza A, Attar E, Gilliland DG, Jacks T, Ebert BL. Coordinate loss of a microRNA and protein-coding gene cooperate in the pathogenesis of 5q- syndrome. Blood. 2011 Oct 27;118(17):4666-73. doi: 10.1182/blood-2010-12-324715. Epub 2011 Aug 26. Citation on PubMed or Free article on PubMed Central
• Starczynowski DT, Kuchenbauer F, Argiropoulos B, Sung S, Morin R, Muranyi A, Hirst M, Hogge D, Marra M, Wells RA, Buckstein R, Lam W, Humphries RK, Karsan A. Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nat Med. 2010 Jan;16(1):49-58. doi: 10.1038/nm.2054. Epub 2009 Nov 8. Citation on PubMed