The chromosomal distribution of sSMC from 2,211 reported cases is shown in Fig. 1. The four syndromes Pallister-Killian, isochromosome 18p, cat-eye and derivative chromosome 22 syndromes, accounted for 31% of cases. Overall, chromosome #15 was the most frequent participant (30%) and was followed by chromosomes #14/#22 (26%), #12 (9%), #18 (7%), #13/#21 (5%), #8 (4%), #1 (~2%), #16 (~2%), #9 (~1%), #3 (~1%), #20 (~1%), X (~1%), and the remainder (~11%). Interestingly, a very similar distribution is observed in neocentric sSMC: chromosome #15 (24%), chromosomes #8 (15%), #13 (15%), #8 (15%), #3 (9%),#1 (7%), #12 (4%), which could be in connection with the mechanisms of sSMC-formation (U-type exchange, summarized in ).
Comprehensive characterization of marker chromosomes is often hampered by the lack of available mul- ticolor-FISH (M-FISH) approaches (such as micro dissection and reverse FISH) , M-FISH applying whole chromosome painting probes (i.e., M-FISH , spectral karyotyping (SKY) , or (sub)centromere-specific probes (cenM-FISH)  and subcenM-FISH) ). Thus, an algorithm was developed that allows determination of the chromosomal origin of an sSMC in a straightforward and effective manner. The chromosomal origin of an sSMC provides better risk assessment of the clinical outcome based on similar cases summarized on the sSMC homepage . A first attempt at genotype-phenotype correlation for sSMC has been reported .
The following algorithm provides a practical method for determining the chromosomal origin of an sSMC for diagnostic laboratories which do not have sophisticated molecular cytogenetic possibilities:
1) Clarify by conventional chromosome-banding analysis of parental peripheral blood if sSMC is de novo. If the sSMC is inherited go to 2); if it is de novo or its parental origin cannot be determined go to 3).
2) If the sSMC is inherited from one clinically normal parent, the identification of the sSMC origin may be replaced by genetic counseling with close monitoring of the pregnancy by high resolution ultrasound examinations. However, an inherited sSMC may be connected with clinical abnormalities in exceptional cases ( case I). If origin of the sSMC is to be clarified, go to 4).
3) If the de novo sSMC is almost the size of chromosome 20 in the same metaphase spread, the presence of a large inverted duplication chromosome 15 (inv dup15), an isochromosome 18 (i(18p) or an i(12p) should be excluded by the appropriate centromeric and/or whole chromosome painting probes. If, as happens in about one-third of cases, the origin of the sSMC is clarified in that way, go to 9). If the origin of the sSMC was not determined in this way, go to 4).
4) If a clear and positive nucleolus organization region (NOR) silver staining result is obtained  for the sSMC, its origin can be determined by hybridizing commercially available centromeric probes for all acrocentric chromosomes, i.e., #13/#21, #14/#22, #15. If, as happens in ~75% of cases, the origin of the sSMC is clarified in this way, go to 9). If the origin of the sSMC was not determined in this way, go to 5).
5) To determine the origin of the sSMC use commercially available centromeric probes, testing sequentially for #8, #1, #20, X, #18, #3 and #12. Even if sSMC was NOR-negative, test for #14/#22, #15 and #13/#21, as cases have been reported with sSMC derived from acrocentric chromosomes, but without NOR . If, as happens in ~90% of cases, the origin of the sSMC is clarified in this way, go to 9). If the origin of the sSMC was not determined in this way, go to 6).
6) To determine if the case is a rare one with a neocentric sSMC, a commercially available pan centromeric probe should be used. This test is important since neocentric sSMC nearly always have a clinically adverse prognosis [2,9,16]. In ~4% of the cases no a-satellite DNA is present on the sSMC. If the sSMC has a-satellite DNA, go to 7); if the sSMC has no a-satellite DNA, go to 8).
7) An sSMC with a-satellite DNA can still arise from 12 different human chromosomes. If there is enough material to continue the analysis, proceed in the following sequence (applying centromeric probes if nothing else is mentioned): #19 (whole chromosome painting probe), #9, #16, #17, #7, #6, #2, #4, #5 (whole chromosome painting probe), #11 and Y. If, as happens in ~100% of cases, the origin of a centric sSMC is clarified, go to 9).
8) To characterize the origin of a neocentric sSMC use FISH, applying the following sequence of whole chromosome painting probes: #15, #8, #13, #3, #1 and #12. If, as happens in ~75% of cases, the origin of the neocentric sSMC is clarified, go to 9).
9) In ~10% of sSMC cases, UPD of the cytogenetically normal sSMC’s sister chromosome has been reported . Because of this, it has been recommended [2,18-19] that, after identification of the origin of the sSMC, the normal sister chromosomes should be tested for their parental origin to exclude possible UPD. This can be tested by molecular genetic approaches, such as microsatellite analysis  or methylation-specific polymerase chain reaction (PCR)  and should be done for every sSMC case in which parental cell material is available. Apart from the chromosomes known to be connected with imprinting (#6, #7, #14, #15, #20), other chromosomes should be tested as uniparental isodisomy can lead to homozygotization of an otherwise recessive, disease-causing gene (e.g., see ).
Figure 1. Frequency of sSMC according to their chromosomal origin: Chromosomal origin of 2,211 sSMC cases collected from the literature . From left to right the most frequent to the most rare. Abbreviations: CES: cat-eye-syndrome; der 22: derivative chromosome 22 syndrome; i(18p): isochromosome 18p syndrome; PKS: Pallister Killian syndrome.