Small supernumerary marker chromosomes (sSMC)

AIM OF THIS PAGE

 Suggestion for management of an sSMC detection

SUBMIT YOUR sSMC CASE

What are sSMC
A definition

What do
sSMC

First description
of sSMC

Synonyms
for sSMC

Frequency
of sSMC

Mosaicism
of sSMC

Euchromatin on sSMC 

UPD and sSMC

How to use this page

Information and links for families with a child having an sSMC (including info in 25 languages !)

LEAFLET   ON   sSMC
created in close co-work with UNIQUE

For (molecular)-cytogenetic laboratories:
special FISH-probes for sSMC characterization

Created by Dr. Thomas Liehr, Institute of Human Genetics and Anthropology, 07740 Jena, Germany; e-mail: i8lith@mti.uni-jena.de

sSMC studies carried out at our institute are approved by the ethical commission of the Friedrich Schiller University (FSU) Jena, Germany  -  internal code 1457-12/04.

=> layman explanations for this page
CLICK HERE (in 25 languages !)
 

=> links to special patient
support groups (see below)
 

 Patient information
as provided by UNIQUE

- for sSMC
- for sSRC(1)
- for sSMC (8)
-  for sSMC(16)
- for PKS
- for inv dup15

1. collect all available case reports on small supernumerary marker chromosomes (sSMC)

 

2. define critical regions for partial trisomies due to the presence of sSMC
 

3. provide information for patients and clinicians
 

4. offer possibility to characterize sSMC in detail

--> contact Dr. Thomas Liehr, Jena: i8lith@mti.uni-jena.de
 

According to {70} "there are several reasons for the difficulty to relate clinical syndromes to the occurrence of sSMC: 
1. sSMC chromosomes can be derived from any chromosome.
2. Even if two sSMC originate from the same chromosome, they still often differ in size and in the content of euchromatic material from either or both arms of a chromosome.
3. Structural variants of sSMC, e.g., ring formation, have been described.
4. Some patients have multiple sSMC of different origin.
5. Single or multiple sSMC often occur in a mosaic form."
6. Silent euchromatin duplication are described - what about silencing in sSMC? {111}

Further information on centromeres see Refs: {154-155}
 

In 1961 - Ilberry et al. {28} describe a 2 year old boy with epicanthic fold, slightly protuberant tongue who had a karyotype 47,XY,+mar[53]/46,XY[16]de novo. The sSMC was a "centric particle" of about the same size as 17p.

This work is not well-known and thus, the work of Froland et al. {8} is often mentioned as first description of sSMC. The latter describe a boy with various congenital defects and a karyotype 47,XY,+mar; the sSMC is metacentric and of comparable size as #21 - and turned out to be a tetrasomy 18p{72}. The case of Froland et al. (1963) was indeed the third to describe an sSMC-case, as in 1962 there was an additional report of Ellis et al. {106}.
 

sSMC           =     small supernumerary marker chromosome 
s-SMC         =      small supernumerary marker chromosome {167}
SMC            =      supernumerary marker chromosome (e.g. {3})
AC / ACH    =     accessory chromosome {58; 73}
SAC             =     small accessory chromosome {74}
ESAC          =      extra structurally abnormal chromosome {14}
                            extra marker chromosome {7}
                            additional marker chromosome {2}
                            supernumerary micro chromosome {9}
                            accessory marker chromosome {10}
                            extra micro chromosome (e.g. {11}) 
                            additional chromosome fragments {32}
                            minute (centric) fragment {33}
                            bisatellited marker chromosomes {102}
                            metacentric chromosome fragment {103}
SRC            =      supernumerary ring chromosome (e.g. {16}) 
SBAC         =      small bisatellited additional chromosomes {93}
NMC          =      neocentric marker chromosome {150}
SMRC        =      supernumerary minute ring chromosome {161}
MC             =      marker chromosome {166}
CaNC         =      cancer associated neochromosomes {177} - exceptionally sSMC can be acquired in neoplasia

Frequency of sSMC according to
their chromosomal origin

Frequency of sSMC in 46,X,+mar

--> in newborn cases the rate is 0.044% [157]

some examples from literature:

0.026%             (16 in 59952 newborn infants) {1 here are taken together: 17-18, 22-27}
0.024%             (  4 in 16395 newborn infants) {2}
0.123%             (  8 in   6500 newborn infants) {3}
0.040%             (  3 in   7536 newborn infants) {4-6 taken together according to 3}
0.054%             (  6 in 11148 newborn infants) {7} 
0.069%             (24 in 34910 newborn infants) {19; 62} 
0.027%             (  4 in 14835 newborn infants) {98}
0.219%             (  4 in   1830 newborn infants) {125}
0.000%             (  0 in     930 newborn infants) {126}
0.027%             (  1 in   3665 newborn infants) {143}

According to {142} sSMC occur in 27.7% of aborted fetuses (9/46 cases) and only in 9.2% (7/76 cases) of term births.
 

---> in prenatal cases the rate is 0.075% [157]

in {153} the following differentiation was done: 20 sSMC in 15792 prenatal cases
the cases were studied due to advanced maternal age [54.16%], increased risk acc. to triple test [19.27%], pathologic ultrasound finding [14.26%], or others

According to {16} the higher rate of cases with sSMC in prenatal compared to newborn can be due to (1) the bias caused by the maternal age effect in prenatal series, (2) the fact that prenatal diagnosis is sometimes performed due to known or suspected fetal pathology ,and/or (3) severely affected fetuses may result in miscarriages and will therefore not be included among newborns.

According to {142} - a study of 1997 - ~50% of pregnancies with sSMC were terminated; 4.4% of the remaining pregnancies ended with stillbirth or spontaneous abortion;  the rest was normal.

According to {116} - a study of 2004 - 20% of pregnancies with cytogenetic aberrations (419 cases) are terminated; 31% of the cases with de novo sSMC are selectively terminated!

According to {158} an sSMC was present in 1/13 pregnancies with exomphalos.

According to {159} an sSMC was present in 1/70 pregnancies with cleft palate.

According to {166}:
in 7/7 inherited sSMC pregnancy continued
in 8/17 pregnancies with de  novo sSMC pregnancy was terminated - i.e. ~50% were terminated in this Italian study
 

---> in mentally retarded the rate is 0.288% [157]

one single center:  0.118%  (in 32930 patients karyotyped in the Belgium center for Human Genetics between 1966 and 1981) {48}

---> in sub fertile people the overall rate is 0.125% [157]
and it differs in male ( 0.165%) versus female 0.022

in Ref. 69 it is suggested that sSMC could disrupt human spermatogenesis - in 142 the influence of sSMC on non-disjunction is discussed.
644 cases with autosomal sSMC collected in that page by 13.Nov. 2004 were specified by their gender:  322/644 where male an 322/644 female

---> 70% of sSMC are de novo [157]

77% de novo           (172 in 241 cases) {151} - 16% maternally, 7% paternally inherited

According to {53; 94} no discernibly increase risk for fetal abnormalities if sSMC is also present in a phenotypically normal parent.

According to this page (12/06/2005) 918/1872 de novo; 111/1872 inherited 943/1872 no information available;
de novo -> 89.2%; inherited ->10,8%; bias!
but: 66/111 maternal origin; 39/111 paternal origin; 6 familial -> concordance with {151}

0.125%            (3 in   2400 adult healthy persons; 2 of the 3 cases were familial) {29}
 

-86%       (i.e. in 38 of 44 cases) {2}
 81%       (i.e. in 17 of 20 cases) {16}
 45%        with satellites (i.e. 14 of 31 cases) {16}
 68%       (i.e. in 26 of 38 cases) {46}

 among mentally retarded
 50% with satellites (i.e. 27 of 54 cases){91}
 

-55%      (i.e. in 21 of 38 cases with acrocentrics) {2}            48%    (i.e. in 21 of 44 cases overall) {2}
 76%      (i.e. in 13 of 17 cases with acrocentrics) {16}           62%    (i.e. in 13 of 20 cases overall) {16}
                                                                                                    only 11 of those 20 are satellited {16}
 46%      (i.e. in 12 of 26 cases with acrocentrics) {46}            32%    (i.e. in 12 of 38 cases overall) {46}

 among mentally retarded
 92%      (i.e. in 25 of 27 cases with acrocentrics) {91}           46%    (i.e. in 25 of 54 cases overall) {91}
 

 137 patients with sSMC

37% with abnormal phenotype
7% couples with reproductive difficulties
47% antenatal diagnosis
9% miscellaneous

59% mosaics - 41% no mosaics

70% de novo; 19% maternal origin; 
11% paternal origin (of 109 of the cases)

36% derived from non-acrocentrics (of 112 cases studied by FISH)
35% derived from #15; 9% from #22

sSMC(15) appearance associated with advanced maternal age
 

Chromosome 

minutes

rings  

inv dup / i / idic

neocentric  

complex 

 markers
(not specified)

Summary 

426

405

1575

97

299

386

  3188

Chromosome 

minutes

rings  

inv dup / i  /idic

neocentric  

complex 

 markers
(not specified)

minutes

rings  

inv dup / i  /idic

neocentric  

complex 

 markers
(not specified)

27

164

289

0

0

63

542

Chromosome 

minutes

rings  

inv dup / i  /idic

neocentric  

complex 

 markers
(not specified)

mosaicism in a fetus with sSMC :

=> big variation of cells with and without sSMC is possible; 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 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. 
 

Euchromatin was detected or excluded on sSMC by different methods:
- Replication banding {49}
- C-bands {58-59}
- DA/DAPI staining for characterization of chromosome 15 - however, its abilities have been questioned {60-63; 75}
- Rx-FISH {50}
- micro dissection and reverse painting (e.g. {51})
- FISH using locus specific probes (e.g. {52})
- association of sSMC with centromeric regions - the more heterochromatin they consist of the better they associate {82-87}