-  sSMC -



Mosaicism in sSMC


Mosaicism in sSMC carriers is present in slightly over 50% of the cases {172}.

Interestingly, non-acrocentric derived sSMC show much more frequently mosaicism than acrocentric ones. sSMC can be present in different mosaic rates, which may go below 5% of the studied cells. Also cryptic mosaicism can be present and mosaics may be differently expressed in different tissues of the body. Even though in the overwhelming majority of the cases somatic sSMC mosaicism has no direct clinical effects, there are also cases with altered clinical outcomes due to mosaicism. Also clinically important is the fact that a de novo sSMC, even present in mosaic, may be a hint on uniparental disomy (UPD). {172}



Mosaicism in phenotypically normal sSMC carriers: 61.9% {42} or 52.3% {43}

Mosaicism in phenotypically abnormal sSMC carriers: 56.6% {42} or 56.3% {43}

Mosaicism in a fetus with sSMC showing a big variation of cells with and without sSMC (see table below).
Thus, cultured amniocytic fluid, chorion or fetal blood is not necessarily representative for the fetus as a whole. [165]




Development of mosaicism during lifetime:

In {88} it was postulated that the percentage of cells with sSMC decrease during lifetime - especially in sSRC cases.

In {64} a case is described with a sSRC with a karyotype 48,XX,+rx2/47,XX+r/47,XX,+r(doublering)/46,XX; here at birth a mosaicism of 0%/77.9%/2.3%/19.8% was described; at 5.5y the patient had a mosaicism of 0.9%/46.6%/4.4%/49.1%. This confirms that theory.

In {96} the authors describe a case with a larger supernumerary marker chromosome which disappeared during the first 6 months of lifetime completely from peripheral blood. It was present first in 6/22 cells (day 12) and declined over 3/57 (day 23) and 2/70 (month 9) to 0/100 (16 months and 2 years).




In parts there are confusing examples for mosaicism:

- Ref. {45}, cases H and I: sSMC 12 in 35% of the cells in a phenotypically normal father and in 100% of son with neurological disorder and facial anomalies. - Similar case is in Ref. {46} case 14;

- Ref. {81} describes a family with different degrees of cells with the Cat-Eye-Syndrome (CES) marker; a child with CES has the sSMC in 100% while mother and two sisters have the sSMC in only 1-60% of the cells; the latter are less or minimal affected. Additionally, the sSMC is present in at least 5 variants in the mother, which look like degraded CES markers.

- Ref. {47} shows similar grades of mosaicism in two generations but variations in the clinical outcome.

- Ref. {45} cases E and F plus B and C: great variations in mosaicism but no phenotypic consequences.