As mentioned before, these are best studied in blood samples. Constitutional abnormalities may occur initially in gonadal tissue of an otherwise normal person. The abnormality may cause difficulties in the normal distribution of chromosomes at meiosis, thus producing imbalanced gametes, showing additional or deleted fragments of chromosomes. If these abnormal gametes are involved in the formation of a zygote, this could develop more or less abnormally depending of the extent of the imbalance. The imbalance could be straightforward duplications, or deletions, or simultaneous duplications and deletions of genetic material. Balanced translocations (where fragments exchange place, with no net gain or loss), could in a minority of cases involve breakpoints cutting through a dominant gene, thus causing a 'single gene' disorder. Large imbalances (roughly, duplications >2% of the length of the haploid autosomal complement, or >1% deletions) cause early death of the embryo or fetus. Lesser imbalances may be compatible with development to term, but the fetus would be more or less abnormal depending on the size and location of the regions involved. At the extreme of cytogenetic resolution we find the microdeletion syndromes, involving regions of about 2Mb of DNA, containing one (as in the case or Rubistein-Taybi syndrome) or more genes. Some clinical databases illustrate the phenotypic effects of duplications and deletions of portions of the karyotype detected by the cytogeneticist.

• The Dysmorphic Human-Mouse Homology Database from the MRC UK is divided in two sections, one giving clinical details and references illustrating partial deletions/duplications by chromosome region, and referring to homologous regions in the mouse. Clinical photographs are not shown on this site. The other section of this site referes to dysmorphisms not associated with chromosome abnormalities.
• The 'Genome Machine' from the University of Washington's Pathology lab shows the morbid anatomy of the human karyotype, i.e. location of known disease genes band by band, (updated 2000) with links to clinical information, based on 'OMIM' searches. (OMIM is the On-line Mendelian Inheritance in Man, the oldest and most complete database on clinical genetics). Notice that from the OMIM page you can go seamlessly to DNA and protein sequence databases, structural data as PDB files, alelic variants databases, etc. But this is beyond the scope of cytogenetics.
• You will find some examples of constitutional chromosome rearrangements in the Dynacare website.

Patient groups. The Aneuploidies, particularly 47,+21 (Down's Syndrome) are the most common cause of referral to the cytogenetics lab. While additional information will be provided in the 'Prenatal' pages with regard to screening programs etc. it is important here to provide a view of Down's Syndrome (and similar syndromes, indeed all syndromes) that goes beyond the act of diagnosis, and beyond blood samples and laboratory procedures. As scientists trained in Genetics we are often asked questions about these frequent and serious problems.

Often what is most useful for the parents and patients is to be alerted to the existence of "patients' organisations", where families can share common problems and solutions, and find a sympathetic hearing for their anxieties as is seldom provided by the health care system. Besides, these patient groups have been instrumental in promoting the cause of research in many places.

The Down Syndrome Quarterly, from Denison University at Granville Ohio, edited by Sammuel J. Thios, contains very useful medical information addressed to parents, patients, educators and health care professionals. Wherever you are, here you could find your nearest branch of a Down Syndrome Association.

For information on patients and families with Cri-du-chat (del5p) click here. Further links to patients' groups will be added here.