Which are the causes of Sacral agenesis / Caudal regression syndrome?

Sacral agenesis, also known as caudal regression syndrome, is a rare congenital disorder that affects the development of the lower spine and spinal cord. It is characterized by the absence or underdevelopment of the sacrum, which is the triangular bone at the base of the spine, as well as abnormalities in the lower limbs and other associated structures. The exact cause of sacral agenesis/caudal regression syndrome is not fully understood, but several factors have been identified as potential causes or contributing factors.

Genetic Factors:

Genetic factors are believed to play a role in the development of sacral agenesis/caudal regression syndrome. Studies have shown that certain genetic mutations or abnormalities can increase the risk of this condition. For example, mutations in the HLXB9 gene have been associated with sacral agenesis. This gene is involved in the development of the lower spine and spinal cord, and mutations can disrupt normal development, leading to the characteristic features of the syndrome.

Maternal Diabetes:

Maternal diabetes, particularly uncontrolled diabetes during pregnancy, has been identified as a significant risk factor for sacral agenesis/caudal regression syndrome. High blood sugar levels in the mother can interfere with the normal development of the fetus, including the formation of the sacrum and other structures in the lower spine. It is believed that the elevated glucose levels can disrupt the delicate balance of cellular processes involved in embryonic development, leading to abnormalities.

Maternal Drug Use:

Exposure to certain drugs during pregnancy has been linked to an increased risk of sacral agenesis/caudal regression syndrome. Drugs such as thalidomide, which was prescribed to pregnant women in the 1950s and 1960s to treat morning sickness but later found to cause severe birth defects, have been associated with this condition. Other drugs, such as retinoic acid derivatives used to treat acne, have also been implicated in the development of caudal regression syndrome.

Environmental Factors:

Environmental factors, such as exposure to toxins or infections during pregnancy, may contribute to the development of sacral agenesis/caudal regression syndrome. Studies have suggested that certain chemicals, such as polychlorinated biphenyls (PCBs) and heavy metals, may increase the risk of this condition. Additionally, maternal infections, such as rubella (German measles), have been associated with an increased incidence of caudal regression syndrome.

Vascular Insufficiency:

Some researchers believe that vascular insufficiency, or inadequate blood supply to the developing fetus, may be a contributing factor in the development of sacral agenesis/caudal regression syndrome. It is hypothesized that disruptions in blood flow to the lower spine and spinal cord during critical stages of embryonic development can lead to malformations and underdevelopment of these structures.

Other Factors:

Other factors that may increase the risk of sacral agenesis/caudal regression syndrome include maternal obesity, advanced maternal age, and certain medical conditions such as spinal cord abnormalities or uterine abnormalities. However, more research is needed to fully understand the role of these factors in the development of the condition.

In conclusion, sacral agenesis/caudal regression syndrome is a complex condition with multiple potential causes or contributing factors. Genetic factors, maternal diabetes, maternal drug use, environmental factors, vascular insufficiency, and other factors may all play a role in the development of this rare congenital disorder. Further research is necessary to better understand the underlying mechanisms and to develop strategies for prevention and treatment.