Congenital Leukemia In Down ’ s Syndrome-A Rare Case Report

Congenital leukemia is a rare disorder presenting in the immediate neonatal period & diagnosed at or within few days of birth. 1 Because of the doubling time of leukemic cells, the disease becomes clinically evident after birth or shortly thereafter. 2 Neonates with Down’s syndrome have an increased risk for congenital leukemia particularly acute megakaryoblastic leukemia (FAB M7). 3 The incidence of acute megakaryoblastic leukemia in Down’s syndrome is estimated to be 400 times than in normal children. 4 We present a case of congenital leukemia in a 22 day old female child with Down’s syndrome who had cyanosis and skin rashes for 2 days. Diagnosis was established on the basis of hematological investigations and cytochemistry of the cells.


Introduction:
Congenital leukemia (CL) is defined as leukemia that develops in utero.It is an extremely rare malignancy associated with very grim prognosis.and a poorly understood natural history. 5Incidence is reported to be 1 per 5 million. 6Neonates with Down's syndrome have an increased risk of CL, a 20 fold increased risk of developing acute leukemia is seen 7 A large proportion of these CLs are of myeloid lineage in contrast to pediatric leukemias which are primarily lymphoid in origin.A characteristic hematopoietic manifestation of Down's syndrome is the occurrence of a transient leukemia like process in the newborn which has a spontaneous clinical and hematological recovery in a week or month's time of diagnosis .The blasts were large in size with fine nuclear chromatin, two to three nucleoli and variable amount of cytoplasm with evidence of cytoplasmic budding.
Cytochemistry was done and it was positive for Sudan Black.The results of chest X-ray were normal.After confirmation of acute myeloid leukemia, combination chemotherapy was started, child improved symptomatically and remission was achieved.

Discussion:
Congenital leukemia is a rare disorder which is diagnosed at, or within few days of birth. 12I Patients with chromosomal anomalies such as Down's and Turner's syndrome.Have higher incidence of CL.
There is a 15-20 times increased risk congenital leukemia in patients with Down's syndrome.80% of the cases are myeloid phenotype 13.Majority of cases of acute myeloid leukemia (AML) are diagnosed on morphology alone.It has recently been known that acute megakaryoblastic leukemia.(AMLM7) is more common in children with Down's syndrome. 8In the present case, the increased percentage of blasts in the peripheral blood & bone marrow indicated a leukemic process.There was no evidence of secondary disorders which could mimic leukemia.Karyotyping confirmed the diagnosis of congenital leukemia in Down's syndrome.
One of the most important manifestations of CL is chloromas, which manifest as nodular infiltration of the skin.They are solid collections of myeloblasts and their most favoured location is in the skin where they are termed as leukemia cutis.The diagnosis is confirmed on biopsy of the involved skin.Most of these patients usually present with petechiae, purpura, hepatosplenomegaly, lethargy, fever and pallor. 14In the present case although skin biopsy could not be performed, cutaneous lesions and hepatosplenomegaly were indicators of extramedullary infiltrates.
Characteristic haematopoietic manifestation of Down's Syndrome is the occurrence of a transient leukemia known as TMD. 8,9,10TMD is reported in about 10% cases of Down's syndrome and is distinguished from congenital AML primarily by spontaneous remission within the first three months of life. 11The essential diagnostic criteria are: proliferation of immature leukemic cells, organ infiltration, no evidence of underlying infective pathology/ hemolysis, and the absence of Down's syndrome or cytogenetic abnormality of 21 st chromosome.

5,10
There is lower blast percentage in marrow than in peripheral smears in TMD.Clonal, cytogenetic abnormality in AML is not seen in TMD.Differentiation is possible only on follow up.Continued clinical or hematological deterioration rules out TMD.In the present case child was followed up after appropriate chemotherapy was instituted and remission was achieved.
Congenital leukemia is a rare malignancy and a poorly understood disorder which can progress rapidly and be fatal if early and adequate treatment is not instituted, hence it is important to differentiate it from myeloproliferative disorders associated with Down's syndrome which have a complete clinical and hematological recovery within weeks or months of diagnosis. 14TMD is transient and recovers spontaneously whereas congenital leukemia is fatal, hence it is important to establish early diagnosis and start the therapy in congenital leukemia.A very close follow up is necessary for all such infants.
Congenital Leukemia In Down's Syndrome-A Rare Case Report