Monosomy 7 is a chromosomal abnormality where a cell is missing an entire copy of chromosome 7 or a significant portion of its long arm (7q). Humans typically have two copies of each chromosome, one from each parent; the absence of one copy deviates from the usual genetic makeup. This genetic change is frequently observed in disorders affecting blood-forming cells, indicating its involvement in hematological conditions.
Understanding Monosomy 7
It involves the loss of one of the two copies of chromosome 7, or a deletion from its long arm (7q). Chromosome 7 contains an estimated 900 to 1,000 genes, which provide instructions for proteins performing various bodily roles. These genes are involved in biological processes, including cell growth and division.
This genetic alteration typically arises spontaneously during cell division and is not usually inherited from parents. However, in some rare cases, a predisposition to monosomy 7 can be inherited, often linked to mutations in genes like SAMD9 or SAMD9L. The loss of chromosome 7, or a part of it, leads to cellular dysfunction due to gene dosage imbalance, affecting normal cell development and function, particularly in the bone marrow.
Associated Conditions and Clinical Features
Monosomy 7 is strongly associated with myeloid neoplasms, cancers affecting blood-forming cells in the bone marrow. It is a common chromosomal abnormality found in Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML), regardless of age or cause.
Individuals with monosomy 7 often experience symptoms from blood cell deficiencies, as the bone marrow may not produce enough healthy blood cells. These symptoms can include fatigue and pallor due to anemia (low red blood cells), recurrent infections from a weakened immune system (low white blood cells), and easy bruising or bleeding issues caused by thrombocytopenia (low platelets). Signs of bone marrow insufficiency, such as petechiae (tiny red spots on the skin caused by bleeding under the surface), may also be present.
Monosomy 7 can also be linked to other health challenges, including developmental abnormalities like prenatal and postnatal growth retardation, and varying degrees of mental and psychomotor impairment. In rare familial cases, monosomy 7 has been associated with other conditions like Noonan’s syndrome, cerebellar ataxia, or Fanconi anemia, highlighting a broader impact on health and development beyond hematological disorders.
Diagnosis and Management Approaches
Monosomy 7 is primarily diagnosed through specialized genetic testing of chromosomes within cells, typically from bone marrow samples. Cytogenetic analysis, such as karyotyping, allows scientists to visualize and count chromosomes to detect the missing chromosome 7 or large deletions. This method identifies the loss of an entire chromosome or significant structural changes.
Molecular techniques are also employed for diagnosis. Fluorescence In Situ Hybridization (FISH) uses fluorescent probes that bind to specific DNA sequences on chromosome 7, allowing detection of smaller deletions not visible with standard karyotyping. Array Comparative Genomic Hybridization (array CGH) provides higher resolution analysis, identifying even smaller genetic gains or losses across the genome.
Management approaches for individuals with monosomy 7 focus on addressing the associated conditions, particularly MDS and AML. Supportive care manages symptoms like anemia through blood transfusions, prevents infections with antibiotics, and controls bleeding. For cases with progressive features of MDS or AML, more intensive therapies are considered. Hematopoietic stem cell transplantation, also known as bone marrow transplant, is often the only potential cure for these associated malignancies.
Prognosis and Genetic Counseling
The prognosis for individuals with monosomy 7 can vary, but its presence generally indicates a more aggressive disease course in associated conditions like MDS and AML. Without aggressive chemotherapy and hematopoietic stem cell transplantation, the outlook is often poor. Even with treatment, nearly half of individuals with monosomy 7 as the primary chromosomal abnormality may succumb to the disease or treatment complications.
Genetic counseling is important for affected individuals and their families. Counselors help families understand the implications of monosomy 7, including its typical spontaneous origin rather than direct inheritance. This understanding is important for family planning and assessing the risk to other family members. Genetic counseling also provides information about potential screenings for at-risk relatives, especially in rare familial instances where a genetic predisposition is identified.