In order to investigate the parental origin of trisomy 21 in families
with more than one child with free trisomy 21 , DNA polymorphism and
cytogenetic analyses were performed.
Eight families with two or three trisomy 21 siblings per families
were studied (families #01-#08). At least 100 blood lymphocytes from each
parent were karyotyped. In only family #02 was mosaic of the paternal blood
lymphocytes observed (3% trisomy 21 cells). DNA polymorphism analysis was
performed in all members of these nuclear families using several single copy
chromosome 21 specific DNA fragments as molecular probes. The parental origin
of the additional chromosome 21 in all affected individuals has been
determined. In each family the additional chromosome 21 in all affected
siblings originated from the same parent. This result be explained by
(i) undetected mosaicism in the parent that contribued the additional
chromosome 21 in more than offspring,
(ii) some unknown predisposing factor that causes recurrence of
trisomy 21, or
( iii) chance alone. Undetected mosaicism (i) has been suggested to be
the most common cause for multiple recurrence of trisomy 21 in siblings.
Three additional families (#09-#11) with two trisom 21 individuals
who are second or third degree relatives were also studied. The results from
DNA polymorphism analysis showed that the parents in whom the nondis junctions
had occurred were not family relatives and, therefore, the finding of two
trisomy 21 individuals in the pedigrees is attributed to chance.
In summary, the extra chromosome 21 originated in the same parent in
families with two or more siblings with trisomy 21; however, in families with
two non-first degree relatives with trisomy 21 the parents responsible for the
trisomy were not blood relatives.