BACKGROUND: Complex small supernumerary marker chromosomes (sSMC) constitute one 
of the smallest subgroups of sSMC in general. Complex sSMC consist of 
chromosomal material derived from more than one chromosome; the best known 
representative of this group is the derivative chromosome 22 {der(22)t(11;22)} 
or Emanuel syndrome. In 2008 we speculated that complex sSMC could be part of an 
underestimated entity.
RESULTS: Here, the overall yet reported 412 complex sSMC are summarized. They 
constitute 8.4% of all yet in detail characterized sSMC cases. The majority of 
the complex sSMC is contributed by patients suffering from Emanuel syndrome 
(82%). Besides there are a der(22)t(8;22)(q24.1;q11.1) and a 
der(13)t(13;18)(q11;p11.21) or der(21)t(18;21)(p11.21;q11.1) = der(13 or 21)t(13 
or 21;18) syndrome. The latter two represent another 2.6% and 2.2% of the 
complex sSMC-cases, respectively. The large majority of complex sSMC has a 
centric minute shape and derives from an acrocentric chromosome. Nonetheless, 
complex sSMC can involve material from each chromosomal origin. Most complex 
sSMC are inherited form a balanced translocation in one parent and are 
non-mosaic. Interestingly, there are hot spots for the chromosomal breakpoints 
involved.
CONCLUSIONS: Complex sSMC need to be considered in diagnostics, especially in 
non-mosaic, centric minute shaped sSMC. As yet three complex-sSMC-associated 
syndromes are identified. As recurrent breakpoints in the complex sSMC were 
characterized, it is to be expected that more syndromes are identified in this 
subgroup of sSMC. Overall, complex sSMC emphasize once more the importance of 
detailed cytogenetic analyses, especially in patients with idiopathic mental 
retardation.