5q minus syndrome
5Q minus syndrome, also known as 5q- syndrome or 5q deletion syndrome, is a rare genetic disorder characterized by the absence of a portion of the long arm (q) of chromosome 5. This deletion impacts the production of blood cells, leading to treatment-resistant anemia, and it is classified under myelodysplastic syndromes (MDSs). The condition predominantly affects older adults, with a higher incidence in women, and is thought to arise from spontaneous gene mutations rather than being inherited.
Patients with 5Q minus syndrome often exhibit symptoms such as low white blood cell counts, elevated platelet counts, and need for red blood cell transfusions due to improperly formed erythrocytes. Diagnosis typically involves a comprehensive blood count and bone marrow biopsy, while a definitive karyotype helps differentiate it from other MDSs. Currently, treatment options are limited; however, the drug lenalidomide has shown promise in improving outcomes for some patients, with a significant portion achieving transfusion independence.
Despite the rarity of this syndrome, understanding its symptoms and potential treatments is critical for affected individuals and their healthcare providers, as there is a risk of progression to acute myeloid leukemia in some cases. The prognosis is generally positive, although ongoing research is necessary to develop more effective therapies.
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5Q minus syndrome
ALSO KNOWN AS: 5q- syndrome, 5q deletion syndrome, 5QMS, partial monosomy 5q, deletion 5q
RELATED CONDITIONS: Myelodysplastic syndrome, acute myeloid leukemia
DEFINITION: 5q minus syndrome is a rare genetic disorder in which a portion of the long arm (q) of chromosome 5 is missing. Production of blood cells is affected, and this syndrome can lead to treatment-resistant anemia. 5q minus syndrome is one in a series of blood disorders collectively called myelodysplastic syndromes (MDSs).
Risk factors: 5q minus syndrome is more common in women than in men and typically occurs in older people. A gene mutation is probably spontaneous and somatic, meaning it is neither inherited nor transmitted to offspring.
Etiology and the disease process: Chromosomes are numbered by size and position of the centromere (point of connection of identical halves). Chromosome 5 is a large chromosome. In 5q minus syndrome, a portion of the deoxyribonucleic acid (DNA) in the long arm (q) is absent, leading to a lack of output from the forty or so missing genes. These genes define the growth and differentiation of cells that manufacture most blood cells. Thus, bone marrow cells are often deformed and have abnormal growth and maturation. Bone marrow hypercellularity is also common, meaning an abnormally large number of hematopoietic cells are present compared to marrow fat. Bone marrow hypocellularity sometimes occurs, with fewer hematopoietic cells present relative to fat. Other missing genes code for interleukins, chemical signals involved in immune protection.
A 2008 study linked 5q minus syndrome with the somatic deletion of one allele of the ribosomal protein S14 (RPS14) gene, which is located on chromosome 5 at 5q31–q33 and codes for a protein in the smaller ribosomal subunit. This abnormal protein thus impairs further ribosome biogenesis, as well as protein synthesis and translation. A 2010 study concluded that 5q minus syndrome is also associated with the loss of two micro-ribonucleic acid (micro-RNA, or miRNA) molecules, miR-145 and miR-146a.
Incidence: The incidence of all MDSs in the general population is approximately two to ten cases per one hundred thousand people, with an estimated 10 to 20 percent of those new cases being chromosome 5 abnormalities. Fewer than one thousand Americans have this disease.
Symptoms: The primary symptoms are anemia, low total white cell count, and increased bone marrow blast and stromal cells. Patients with 5q minus syndrome also have elevated platelet counts, something that distinguishes this group from other myelodysplastic syndromes. Because red blood cells are not manufactured properly (abnormal erythrocyte morphology), patients are anemic, experience abnormal bleeding, and require regular transfusions of red blood cells. In many cases, this anemia fails to respond to transfusions or other stimuli.
Screening and diagnosis: Total white blood cell count, monocyte and platelet count, and bone marrow biopsy are the best diagnostic tools. A definitive karyotype (analysis of chromosome count and pattern) helps set 5q minus syndrome apart from other myelodysplastic syndromes.
Treatment and therapy: There have been few breakthroughs in therapy. Hematopoietic growth factors and granulocyte-macrophage colony-stimulating factors have been tried with little success. Immunosuppressive drugs do not help most patients. One study involving the experimental leukemia drug lenalidomide (LEN) showed substantial improvement to the point of being transfusion-independent and going into cytogenic remission (the genetic abnormality was no longer displayed). Further study revealed that LEN renders blood transfusions unnecessary in two-thirds of cases. However, in 35 percent of 5q minus syndrome cases, the patient will not respond to or tolerate LEN.
Prognosis, prevention, and outcomes: Due to the rarity of this disease, prognosis is difficult to quantify. It is generally positive, although progression to acute leukemia may occur. In a LEN trial in the late 2000s, 45 percent of patients entered complete cytogenic remission, and another 28 percent entered minor remission. Only 6 percent progressed to acute myeloid leukemia or a more severe form of MDS. Further study found that patients live an average of 23 months following LEN failure.
Bibliography
"Chromosome 5q Deletion." National Organization for Rare Disorders, rarediseases.org/gard-rare-disease/chromosome-5q-deletion. Accessed 20 June 2024.
Elkattawy, Sherif, et al. "5q Deletion Myelodysplastic Syndrome in a Young Male Patient." Cureus, vol. 13, no. 8, 2021, doi.org/10.7759/cureus.17466.
Gaballa, Mahmoud, and Emmanuel Besa. "Myelodysplastic Syndromes with 5q Deletion: Pathophysiology and Role of Lenalidomide." Annals of Hematology, vol. 93, no. 5, 2014, pp. 723–33. doi:10.1007/s00277-014-2022-3.
Giagounidis, Aristoteles A. N., and Carlo Aul. "The 5q– Syndrome." Rare Hematological Malignancies. Ed. Stephen M. Ansell. Springer, 2008. 133–48.
Gurnari, C., et al. "Myelodysplastic Syndromes with Del(5q): A Real-Life Study of Determinants of Long-Term Outcomes and Response to Lenalidomide." Blood Cancer Journal, no. 12, no. 132, 2022. doi.org/10.1038/s41408-022-00724-3.
"Myelodysplastic Syndrome Associated with Isolated Del(5q) Chromosome Abnormality." Genetic and Rare Diseases Information Center, June 2024, rarediseases.info.nih.gov/diseases/8723/5q-syndrome. Accessed 20 June 2024.