Down syndrome is usually caused by complete trisomy 21. Rarely, it is due to 
partial trisomy of the segment 21q22. We report on a 33-month-old girl with 
tetrasomy 21 pter-->q22.1 resulting from an extra chromosome idic(21)(q22.1). 
She has craniofacial traits typical of Down syndrome, including brachycephaly, 
third fontanel, upward slanting palpebral fissures, round face, and protruding 
tongue. Speech development is quite delayed whereas motor development is only 
mildly retarded. The molecular content of the extra isodicentric chromosome was 
defined by molecular genetic investigations using 13 single copy probes unique 
to chromosome 21, and SOD1 expression studies. The child was found to have 4 
copies of the region defined by D21S16 (21cen) through D21S93 on 21q22.1 and two 
copies of the remaining region defined by SOD1-->D21S55-->D21S123. In view of 
the recent assignment of Down syndrome facial characters to the 21q22 region, 
defined in part by D21S55, it is significant that this child shows a subset of 
Down syndrome facial manifestations, without duplication of this region. These 
results suggest that genes contributing to the facial and some of the hand 
manifestations of Down syndrome also exist in the chromosomal region proximal to 
D21S55 in band 21q22.1.