During the last few years, new cases with certain micro-deletions and micro-duplications have been de­scribed, revealed by FISH analysis and attributed to the subtelomeric regions of the chromosomes. New genetic syndromes are being added to the already existing cata­logue of micro-deletion and micro-duplication syndromes. Thus far, at least 20 cases have been published which can be attributed to a terminal 22q13 deletion syndrome, and may represent a recognizable phenotype with the follow­ing main features: normal or advanced growth, signifi­cantly delayed speech, pervasive behaviors, and minor facial dysmorphism [37].

Subtelomeres. Subtelomeric DNA probes identify DNA regions at a distance of 30-450 kb from the very end of the chromosome. Subtelomeric abnormalities are found in 7-10% of patients with a positive family history, dys­morphic features and mild or severe mental retardation of unknown origin [38]. Specific phenotypes for 1pter [39], 1qter (40) and 2qter [41,42] micro-deletions are recog­nized in many genetic centers (Fig. 5). Research projects of couples with more than five spontaneous abortions and normal karyotypes are in progress [43].

Subtelomeres That are Available. Ready to use DNA subtelomeric probes are sold for 41 out of 48 human chro­mosome subtelomeres. The subtelomeric probes of the short (p) arms of the five acrocentric chromosomes are not available, while the subtelomeric probes of the short and long arms of the X and Y chromosomes have the same sequence, so we cannot distinguish them.

Basic Rules for the Study of Micro-Deletions and Micro-Duplications in Human Chromosomes. 1) Careful selection of the patients from the clinical geneticist. 2) Good knowledge and experience of the FISH technique by a responsible cytogeneticist. 3) A laboratory equipped with FISH probes, fluorescent microscope with special filters, and automated analysis FISH system. 4) A molecu­lar geneticist with good knowledge and experience and who might proceed to molecular analysis if this is needed.

Table 1. Syndromes with micro-duplications.

Table 2. Syndromes with micro-deletions.