Pediatric Myelodysplasia Clinical Presentation

Updated: May 17, 2023
  • Author: Natalia Dixon, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
  • Print


Patients with myelodysplasia may present with symptoms of hematopoietic failure, including infection, bleeding, bruising, fatigue, weight loss, and dyspnea upon exertion. However, no clinical symptoms are reported in up to 20% of children with RCC, in whom cytopenia(s) or isolated splenomegaly is discovered during routine evaluation for an unrelated symptom. Three quarters of patients with RCC have a platelet count of below 150,000, while anemia with a hemoglobin concentration of less than 10 g/dL is noted in about half of the affected children. Macrocytosis (defined by the patient’s age) is seen in most. The white blood cell count is decreased in many patients, and severe neutropenia is noted in about 25%. [21] The interval between onset of symptoms and diagnosis ranges from 0-23 months, with a median of 2 months.

Eliciting a prior history of malignancy or cytotoxic therapy is important to distinguish between de novo versus secondary myelodysplasia syndrome (MDS). Specifically, a history of previous exposure to alkylating agent chemotherapy, epidophyllotoxin, radiation therapy, or hematopoietic stem cell transplant is important as these are risk factors for therapy-related myelodysplasia syndrome. [22] A constitutional bone marrow failure syndrome (eg, Fanconi syndrome, Diamond-Blackfan anemia, Kostmann syndrome, Shwachman-Diamond syndrome) or aplastic anemia can also precede secondary myelodysplasia syndrome. Familial cases of myelodysplasia syndrome have also been reported; the history is usually that of a first-degree relative with myelodysplasia syndrome, AML, or both.



The physical examination often reveals the degree of cytopenia (eg, symptoms of pallor, bruising, petechiae). Splenomegaly and hepatomegaly are more common in childhood myelodysplasia syndrome and predominate in JMML. A pathognomonic erythematous maculopapular rash is seen in one third of children with JMML. Congenital anomalies and syndromic features are significant because of the association of myelodysplasia syndrome with several constitutional disorders, as described in Causes.



A feature unique to childhood myelodysplasia syndrome is that in about 25% of children there is an associated syndrome or congenital abnormality. Known inherited predispositions to the development of myelodysplasia syndrome include NF type 1 (NF-1), Fanconi anemia, severe congenital neutropenia (Kostmann syndrome), Down syndrome, Noonan syndrome, Shwachman-Diamond disease, Diamond-Blackfan anemia, dyskeratosis congenita, and Dubowitz syndrome. Bloom syndrome, Poland syndrome, and ataxia telangiectasia have also been associated with preleukemia.

A study by Zubovic et al found 291 differently expressed genes in patients with pediatric myelodysplasia syndrome, with these genes playing a role in the regulation of apoptosis and the cell cycle, ribosome biogenesis, inflammation, and adaptive immunity. The investigators suggested that the genes may provide new molecular biomarkers and treatment targets. [23]

The most recent pediatric classification systems for myelodysplasia syndrome have designated Down syndrome–related diseases (eg, transient myeloproliferative disorder, myeloid leukemia of Down syndrome) as unique and separate from myelodysplasia syndrome classification in other children. [24] This is based on the unique mutations, molecular phenotype, and therapy response seen in this population.

As the population of childhood cancer survivors increases, treatment-related myelodysplasia syndrome following cytotoxic chemotherapy is of more concern in the pediatric population. [25, 26] The most common association is with prior alkylator therapy, with or without concomitant radiation. The risk of myelodysplasia syndrome peaks 5-7 years after alkylator treatment and is related to cumulative dose. A strong association with monosomy 7 or del7q is recognized.