Complex small supernumerary marker chromosomes – an update

Abstract

BackgroundComplex 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.ResultsHere, 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.ConclusionsComplex 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.

Impaired Spermatogenesis due to Small Supernumerary Marker Chromosomes: The Reason for Infertility Is Only Reliably Ascertainable by Cytogenetics

“…Still, there are also acrocentric-derived sSMCs which cannot be attributed to one of the 5 acrocentrics, as they may be even neocentric [Klein et al, 2012]. A detailed characterization of the sSMCs is nonetheless imperative, as there are also cases included here which need more attention and clinical care, like such with a complex sSMC derived from more than 1 chromosome (case 156) [Liehr et al, 2013b] or such with an sSMC formed by McClintock mechanism (cases 195-198) [Baldwin et al, 2008]. In contrast to most other sSMCs, here the offspring may be affected by severe clinical symptoms due to a possible inheritance of an imbalanced sSMC [Liehr, 2018].…”

Complex Small Supernumerary Marker Chromosome Leading to Partial 4q/21q Duplications: Clinical Implication and Review of the Literature

“…The clinical features of the patients with sSMcs derived from chromosomes 4 and 21 were available in only 4 cases. One of the patients [Liehr et al, 2013], listed in the online database of sSMCs [Liehr 2018], has breakpoints in chromosomes 4 and 21 similar to those of our patient, but the only clinical information available was mental retardation, developmental delay, and facial abnormalities. The other sSMC with similar breakpoints [Aurias et al, 1978] has no clinical data available.…”

“…Complex sSMCs derived from chromosome 4 and 21 are very rare and have been reported in the literature in only 7 patients [De la Chapelle et al, 1973;Pfeiffer et al, 1977;Aurias et al, 1978;Kitsiou-Tzeli et al, 1984;El-Ruby et al, 2007;Liehr et al, 2013;Tachon et al, 2015]; 2 of them are listed in the online database of sSMCs [Liehr, 2018]. All cases with available data were females with a derived chromosome inherited from maternal translocations.…”

47,XY,+der(X)t(X;18)(p11.4;p11.22): A Unique Aneuploidy Associated with Klinefelter Syndrome due to an Extra Derivative X Chromosome Inherited Maternally

“…Interestingly, complex small supernumerary marker chromosomes could also lead to the gain of 18p material. Although these special cases are not included in the present study due to the presence of structural anomalies other than chromosome 18, they deserve further investigation [Liehr et al, 2013]. Finally, 12 cases in 8 reports were included and summarized in table 1 .…”