Chromosome 5q deletion syndrome

Overview

Chromosome 5q deletion syndrome, often referred to as the “5q- syndrome,” is a distinct subtype of myelodysplastic syndromes (MDS), a group of bone marrow disorders characterized by ineffective blood cell production. It is defined by the deletion of a portion of the long arm (q arm) of chromosome 5, specifically involving band 5q31 or 5q32. This syndrome is most commonly seen in older adults and is particularly noted for causing macrocytic anemia (enlarged red blood cells) and low or normal white blood cell counts, with relatively preserved platelet levels. It is more common in females and has a better prognosis than other forms of MDS.

Causes

The primary cause of chromosome 5q deletion syndrome is the loss of genetic material on chromosome 5q, usually in the form of a somatic (acquired) deletion in bone marrow cells. This deletion impacts several genes that are essential for normal hematopoiesis (blood cell development), including:

• RPS14: Associated with impaired red blood cell formation

• CSNK1A1: Implicated in cell cycle regulation

• APC, EGR1, and others: Tumor suppressor genes whose loss may contribute to MDS progression

The deletion is not inherited; it develops over time, usually in older individuals, and is linked to aging or exposure to certain toxins or chemotherapy agents in rare cases.

Symptoms

Symptoms of 5q deletion syndrome are generally due to cytopenias (low blood cell counts), with red blood cell deficiency being most prominent. Common symptoms include:

• Fatigue and weakness: Due to anemia

• Pale skin and shortness of breath

• Increased risk of infection: If white blood cell counts are low

• Easy bruising or bleeding: Though platelet counts are often preserved or elevated

• Rarely, symptoms of progression to acute myeloid leukemia (AML)

Diagnosis

Diagnosis of 5q deletion syndrome involves a combination of clinical evaluation, blood tests, bone marrow analysis, and cytogenetic studies. Diagnostic steps include:

• Complete blood count (CBC): Typically shows macrocytic anemia with normal or high platelet counts

• Bone marrow biopsy: Reveals dysplastic changes, especially in red cell precursors and megakaryocytes (platelet-producing cells)

• Cytogenetic analysis: Confirms deletion of chromosome 5q in the bone marrow cells

• Fluorescence in situ hybridization (FISH): Can detect the specific 5q deletion

• Molecular testing: To check for additional mutations that may influence prognosis or treatment

Treatment

Treatment for 5q deletion syndrome depends on the severity of symptoms, blood counts, and progression of disease. Common management strategies include:

• Lenalidomide: An immunomodulatory drug that is particularly effective in patients with isolated 5q deletion; it can improve red blood cell counts and reduce transfusion dependence

• Supportive care: Including blood transfusions and iron chelation therapy to manage anemia

• Growth factors: Such as erythropoiesis-stimulating agents (ESAs) in some cases

• Allogeneic stem cell transplantation: Considered in younger patients or those with disease progression, though rarely needed due to the generally favorable prognosis of 5q- syndrome

Prognosis

Chromosome 5q deletion syndrome has a relatively good prognosis compared to other forms of myelodysplastic syndrome. Many patients respond well to lenalidomide, with significant improvement in blood counts and quality of life. The risk of progression to acute myeloid leukemia (AML) is lower than in other MDS subtypes. Regular follow-up is necessary to monitor blood counts and detect any signs of disease progression. Overall, with appropriate management, patients with 5q- syndrome can often achieve long-term disease control.