Down’s syndrome is a genetic disease of children and the commonest cause of intellectual debility. Humans normally have 46 somatic chromosomes and 2 sex chromosomes (X&X or X&Y). In most of the patients with Down’s syndrome, there is an extra chromosome on the 21st. position of the somatic chromosomes. Thus, there are 3 chromosomes instead of 2 in the 21st. position. So, the defect is also known as Trisomy 21. Many problems like intellectual disability, cardiac defects and abnormal physiologic functioning are a result of this genetic defect. For Down Syndrome Awareness Month 2022, OnlyMyHealth editorial team spoke to Dr. Santanu Basu, Consultant Haematologist, Manipal Hospital, Kolkata, to know why children with down's syndrome are more prone to leukaemia.
Why are children with Down's syndrome more prone to leukaemia?
Patients with Down’s syndrome have a unique spectrum of malignancies including leukaemia and solid tumours. Studies have shown that Down’s babies have a 10-20-fold increased relative risk of leukaemia. Both Acute Lymphoblastic leukaemia (ALL) and Acute myeloblastic leukaemia (AML) can occur in DS children. Unlike other babies, they have a 50-50 chance of developing AML and ALL. This is different from what happens in non-DS children. Children generally have more ALL than AML.
Symptoms of leukaemia in children with down syndrome
The symptoms of Leukaemia in children with Down syndrome are generally the same which include high temperature, frequent bruising with no apparent reasons, being more fatigued than usual, getting recurrent infections, abdominal swelling, getting blood spots or rashing in the skin, pain in bones and joints, loss of appetite to name a few. So look for the early signs and consult your doctor:
- If the child persists in having infections, or if a contemporary infection is not showing any sign of getting better, it’s crucial to consult with a specialist.
- It’s also necessary to lower the child’s vulnerability to imaging examinations that comprise radiation to a feasible extent which includes X-rays and CT scans, which may further increase the child’s peril of leukaemia.
- The paediatrician can run some blood tests to help verify preadolescence leukaemia. Based on the results, they may refer the child to a paediatric oncologist, who specialises in cancer diagnoses and treatments.
Acquired gain of function mutation of the Janus kinase 2 gene (due to trisomy) is present in 30% of ALL babies, making it a potential cause of leukemogenesis. Another mutation in the GATA1 gene is seen in the immature cells (blast cells) of babies with DS having transient myeloproliferative disorder (TMD) and AML. The GATA1 gene encodes for a transcription factor that helps in the maturation of blood cells like megakaryocytes (mother cell of platelets) & others. Mutation of the GATA1 gene in DS leads to uncontrolled proliferation of immature megakaryocytes resulting in Acute megakaryocytic leukaemia, an otherwise rare variant of AML.
Treatment for children with leukaemia and down syndrome
Treatment for children with Down syndrome and leukaemia is typically the same as the treatment for individuals without the disease, which is chemotherapy. Chemotherapy functions by diminishing the number of blast cells (basic immature cells from which specialised cells develop) in the body. There are a number of other types of treatments which can treat Leukaemia as follows:
- Stem cell transplant
- Car T-cell Therapy
The first reported leukaemia in DS patients was in 1930 and the first systematic study occurred in 1957. Research on the cause of leukemogenesis in DS is an ongoing effort and takes time due to the relative rarity of the disease. We are still uncovering new mechanisms for the development of leukaemia in these unfortunate babies.