Transient myeloproliferative disorder of Down syndrome
- Johann Hitzler, MD, FRCP(C), FAAP
Johann Hitzler, MD, FRCP(C), FAAP
- Associate Professor, Department of Pediatrics
- University of Toronto
- Moira Garraus, MD
Moira Garraus, MD
- Paediatric Oncologist
- Hospital San Joan de Deu
Down syndrome (DS, constitutional trisomy 21, OMIM #190685) is the most common chromosome abnormality among live born infants. It is the most frequent form of intellectual disability caused by a microscopically demonstrable chromosomal aberration.
The syndrome manifests as developmental delay and a spectrum of congenital malformations that may include the heart (eg, atrioventricular septal defect), gastrointestinal tract (eg, duodenal stenosis or atresia, imperforate anus, Hirschsprung disease), musculoskeletal system, and other organs. (See "Down syndrome: Clinical features and diagnosis".)
Hematologic abnormalities affecting red blood cells, white blood cells, and platelets are common in DS, particularly during childhood. Population-based studies show that risk for leukemia is 10 to 20 times higher in individuals with DS compared with the overall population, with a particularly striking increase of the incidence of acute myeloid leukemia (AML) in young children with DS (approximately 150-fold). (See "Down syndrome: Clinical features and diagnosis", section on 'Hematologic disorders'.)
In addition, children with DS frequently develop a transient myeloproliferative disorder (TMD) during the newborn period and early infancy (also termed transient leukemia and transient abnormal myelopoiesis). This pre-leukemic disorder poses diagnostic challenges, requires a differentiated approach to management, and plays an important pathogenetic role in the development of AML in children with DS.
The clinical features, diagnosis, and management of TMD of DS will be presented here. The epidemiology, clinical features, diagnosis, and general management of children with DS are discussed separately. (See "Down syndrome: Clinical features and diagnosis" and "Down syndrome: Management".)
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- DISEASE MECHANISM
- CLINICAL PRESENTATION
- Spectrum of disease
- Organ involvement
- Laboratory features
- - Peripheral smear and bone marrow
- - Coagulation studies
- - Liver function tests
- Evaluation of suspected cases
- Diagnostic criteria
- DIFFERENTIAL DIAGNOSIS
- PROGNOSIS AND COURSE
- Early death from TMD
- Development of AML of DS
- Indications for therapy
- Low-dose cytarabine
- Management of complications
- SUMMARY AND RECOMMENDATIONS