DNMT3A Gene

DNMT3A overgrowth syndrome is a disorder characterized by faster than normal growth before and after birth, subtle differences in facial features, and intellectual disability.

Individuals with DNMT3A overgrowth syndrome are often longer than normal at birth and are taller than their peers throughout life. Many affected individuals become overweight in late childhood or adolescence. They may also have an abnormally large head size (macrocephaly).

The characteristic facial appearance of individuals with DNMT3A overgrowth syndrome includes a round face; thick, horizontal eyebrows; and narrowed openings of the eyes (narrowed palpebral fissures). Additionally, the upper front teeth are often larger than normal.

Intellectual disability in DNMT3A overgrowth syndrome ranges from mild to severe. Individuals may have features of autism spectrum disorder, which are characterized by impaired communication and socialization skills.

Individuals with DNMT3A overgrowth syndrome may have other signs and symptoms, including a rounded upper back that also curves to the side (kyphoscoliosis), heart defects, flat feet (pes planus), weak muscle tone (hypotonia), or joints that are loose and very flexible (hypermobile joints). Psychological disorders such as depression, anxiety, or obsessive-compulsive disorder can also occur in this disorder.

Core binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer of the blood-forming tissue (bone marrow) called acute myeloid leukemia. In normal bone marrow, early blood cells called hematopoietic stem cells develop into several types of blood cells: white blood cells (leukocytes) that protect the body from infection, red blood cells (erythrocytes) that carry oxygen, and platelets (thrombocytes) that are involved in blood clotting. In acute myeloid leukemia, the bone marrow makes large numbers of abnormal, immature white blood cells called myeloid blasts. Instead of developing into normal white blood cells, the myeloid blasts develop into cancerous leukemia cells. The large number of abnormal cells in the bone marrow interferes with the production of functional white blood cells, red blood cells, and platelets.

People with CBF-AML have a shortage of all types of mature blood cells: a shortage of white blood cells (leukopenia) leads to increased susceptibility to infections, a low number of red blood cells (anemia) causes fatigue and weakness, and a reduction in the amount of platelets (thrombocytopenia) can result in easy bruising and abnormal bleeding. Other symptoms of CBF-AML may include fever and weight loss.

While acute myeloid leukemia is generally a disease of older adults, CBF-AML often begins in young adulthood and can occur in childhood. Compared to other forms of acute myeloid leukemia, CBF-AML has a relatively good prognosis: about 90 percent of individuals with CBF-AML recover from their disease following treatment, compared with 25 to 40 percent of those with other forms of acute myeloid leukemia. However, the disease recurs in approximately half of them after successful treatment of the initial occurrence.