The Principles of Clinical Cytogenetics - Extra Materials - Springer

Autosomal Aneuploidy 141
Fig. 5. The hand of a Down syndrome child showing small hand, clinodactyly, only one crease in the fifth
finger, and single palmar crease.
Down syndrome patients of all ages, with a bimodal age of onset in the newborn period and again at
3–6 years (56). Moreover, a transient myeloproliferative disorder (TMPD) in the newborn period,
characterized by a high spontaneous remission rate with occasional relapse, occurs more frequently
in children with Down syndrome. Of interest is the observation of the presence of a trisomy 21 clone
in association with TMPD in 15 phenotypically normal children, at least four of whom were determined
to be constitutional mosaics for Down syndrome (57).
Overall, the clinical phenotype is typically milder in mosaic Down syndrome patients, but there is
no clear correlation between the percentage of trisomy 21 cells and the severity of clinical presentation.
This can be as severe in mosaic patients as in nonmosaic trisomy 21 individuals.
Delineation of the regions of chromosome 21 responsible for the Down syndrome phenotype has
been attempted using molecular methods to study patients with partial trisomy 21 who present clinically
with various features of the syndrome (58–63). These studies suggest that the genes for CuZn–
superoxide dismutase (SOD1) and amyloid precursor protein (APP), located proximal to band
21q22.1, can be excluded from a significant contribution to the Down syndrome phenotype, whereas
parts of bands 21q22.2 and 21q22.3, including locus D21S55, can be the minimal region necessary
for the generation of many Down syndrome features (see Chapter 3 for a discussion of band nomenclature).
Studies by Korenberg et al. suggest that, instead of a single critical region, many chromosome
21 regions are responsible for various Down syndrome features (64). They used a panel of cell
lines derived from 16 partial trisomy 21 individuals to construct a “phenotypic map” correlating 25
Down syndrome features with regions of chromosome 21.