SNP Shot: Genomic Insights

Diamond-Blackfan anemia (DBA) is a condition that primarily affects the bone marrow, often accompanied by physical abnormalities in various parts of the body.

The bone marrow's main job is to create new blood cells. In DBA, the bone marrow doesn't function properly, failing to produce enough red blood cells. These cells are vital for carrying oxygen throughout the body. This deficiency of red blood cells, known as anemia, usually becomes noticeable within the first year of life. Common symptoms of anemia include tiredness, weakness, and unusual paleness.

Individuals with DBA face an elevated risk of several serious complications stemming from their bone marrow dysfunction. They are more likely to develop myelodysplastic syndrome (MDS), a condition where immature blood cells don't mature correctly. Furthermore, they also have a heightened risk of developing acute myeloid leukemia (AML), a cancer of the bone marrow, as well as osteosarcoma, a type of bone cancer, and other types of cancer.

About half of those with DBA exhibit physical abnormalities. These can include an unusually small head (microcephaly), a low frontal hairline, and characteristic facial features such as widely spaced eyes (hypertelorism), drooping eyelids (ptosis), a wide and flat nasal bridge, small and low-set ears, and a small lower jaw (micrognathia). Some individuals may also have a cleft palate, sometimes with a cleft lip. Other possible abnormalities include a short, webbed neck; shoulder blades that are smaller and positioned higher than normal; and hand abnormalities, most commonly affecting the thumbs. Roughly one-third of individuals with DBA experience slow growth, resulting in short stature.

Other potential features of DBA can involve eye problems such as cataracts (clouding of the lens), glaucoma (increased eye pressure), or strabismus (misaligned eyes). Kidney abnormalities, structural heart defects, and, in males, hypospadias (urethral opening on the underside of the penis) can also occur.

The severity of DBA can vary considerably, even within the same family. Increasingly, individuals with "non-classical" DBA are being identified. This form typically presents with milder symptoms. For example, some individuals may experience mild anemia that starts later in childhood or adulthood, while others may exhibit some of the characteristic physical features without having bone marrow problems.

Inheritance:

DBA is inherited in an autosomal dominant manner, meaning that having one copy of the mutated gene in each cell is enough to cause the condition. In approximately 45% of cases, a person with DBA inherits the altered gene from one affected parent. The remaining cases arise from new genetic mutations and occur in individuals with no family history of the disorder.