Tetrasomy 21 pter→q22.1 and Down syndrome: Molecular definition of the region

Abstract

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.

Partial trisomy and tetrasomy of chromosome 21 without Down Syndrome phenotype and short overview of genotype-phenotype correlation. A case report

“…However, some facial features (brachycephaly, macroglossia, etc.) and further minor abnormalities (hypotonia, joint hyperlaxity) are determined by loci proximal to DSCR 1, which is consistent with our observation 7,14,15 . In recent studies the nonexistence of single region (DSCR) responsible for all the most severe DS features has been expressed 16,17 .…”

“…Speech was especially delayed and defective, and in most patients particular behavioural abnormalities were observed, such as motor incoordination, restlessness and etc. 3,[6][7][8] . Another patient with trip(21)(pter-q22.1) idic(21)(q22.1) did not exhibit Down syndrome phenotype; however brachycephaly, round face and prominent lower lip were described 6 .…”

Whither Down syndrome critical regions?

“…The finding that tetrasomy for 21p-21q proximal permits the diagnosis of DS (Daumer-Haas et al 1994), when trisomy for this segment usually does not, supports the idea that it may be the amount of superfluous transcribing genetic material that contributes significantly to the DS phenotype. Continued mapping of chromosome 21 is certainly worthwhile as part of the acquisition of complete knowledge of the human genome.…”

Significance of oral health in persons with Down syndrome: a literature review

“…The structural features discussed can be directly related to the chromosomal abnormality 22 . The functional manifestations of these abnormalities are indirectly related to the underlying pathology.…”