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An extremely premature male neonate presented with an unusual multisystem dysfunction within the first 24 to 48 hours of life. The unfolding of clinical events and investigations revealed a transient myeloproliferative disorder (TMD). TMD was the main indication for karyotyping of this premature infant without clinical symptoms of Down syndrome. The awareness of TMD in a newborn warrants karyotype analysis to look for trisomy 21 and a close surveillance because of its potential progression to true leukaemia.