tl_files/tiny_templates/Bilder TL/Header-sSMC.jpg

- sSMC -

CHROMOSOME 18

References

 

             
  Cases without
clinical findings
17 Cases with
clinical findings
21 symptoms  
  similar imbalances - no clinical findings similar imbalances with clinical findings  
    Cases with
isochromosome 18p
309    
  Cases with
unclear clinical correlation
Cases with
neocentromeres
2 tumor
0
 
  similar imbalances  
      DISCLAIMER      

In general 70% of sSMC carriers are clinically normal. The figures here
are based on the bias, that mainly clinically aberrant cases are reported in literature!

           
  UPD (uniparental disomy) cases: UPD 18
mat
UPD 18
pat
UPD 18
unclear
 
           

 


the probably non-dosage sensitive pericentric region of chromosome 18


SCHEMATIC CYTOGENETIC DEPICTION

tl_files/tiny_templates/Bilder TL/sSMC/sSMC-18.jpg



SCHEMATIC MOLECULARGENETIC DEPICTION

acc. to UCSC Genome Browser on Human Mar. 2006 assembly [UCSC hg18, 2006]
and available BAC-data/ array-data from cases marked *** mentioned below [MB]

 

critical region 12.59 --- 12.80 uncritical region [15.40 centromere 17.30] uncritical region 18.12 --- 19.34 critical region

Below adapted for UCSC hg19, 2009

critical region 12.60 --- 12.80 uncritical region [15.40 centromere 19.00] uncritical region 19.87 --- 21.08 critical region

 


Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region 18p - proximal 18q - proximal
symptoms
aggressive behavior 0 % 17 %
anal atresia 0 % 17 %
brain malformation 25 % 0 %
developmental delay 75 % 33 %
dysmorphic face 75 % 17 %
finger or toe/foot malformations 50 % 50 %
genital abnormalities 50 % 33 %
growth retardation 0 % 33 %
hearing problems/ loss 50 % 0 %
heart defect 25 % 17 %
hypotonia 0 % 17 %
kidney problems/ malformations 0 % 17 %
mental retardation 50 % 0 %
obesity 0% 33 %
overgrowth 25 % 0 %
urethral problems 0 % 50 %
number of cases (marked with “°” below) 4
6
 

References

Cases without clinical findings (O)

 

 
  case no. gender/
age at diagnosis
studied
material
de novo/
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  18-O-
p11.22/
1-1
female/
prenatal
AF PBL n.a. AF: 47,XX,+mar[35%]/
46,XX[65%]
PBL: 47,XX,+mar[4]/
46,XX[11]
min(18)(:p11.22q11.1:)[10]/
min(18)(:p11.22
q11.1:
:q11.1
p11.22:)[1]
FISH-data: RP11-151D11(13.08MB) on sSMC
cenM;
subcenM;
advanced maternal age, ultrasound normal in week 19+3; normal child born and normal at 10 and 16m
 
{0} provided of Drs. Prager and Junge, Dresden, Germany  
  18-O-
p11.21/
1-1
female/
35y
PBL n.a. 47,XX,+mar[23]/
46,XX[17]
min(18)(:p11.21q11.1:)
FISH-data: RP11-151D11(13.08MB) on sSMC
min(18)(:p11.21
q12.1:)
aCGH: 11.64-24.94 MB
?can be mosaic?
cenM;
subcenM;
aCGH
ICSI-patient of 36 years; primary sterility; she had a surgery at the age of 7 due to a artrial septal defect {1} case 27
{104} case 95
{0}
{158} case Sm-7
{171} case 18-1
 
  18-O-
p11.21/
1-2
male/
6y
PBL
(EKF-
cellbank)
maternal
(mar in ~26%)
47,XY,+mar[21]/
46,XY[2]
12 years later mar only in 25/34
FISH: min(18)(:p11.21q11.1:)
array + FISH:
min(18)(:p11.22
p11.21:)
FISH-data: RP11-151D11(13.08MB) on sSMC
array: 13.99MB - centromere
cenM;
subcenM; array CGH
normal healthy young man; mother healthy as well {88} case A; mother case B
{95} case 11
 
  18-O-
p11.21/
1-3
female/
31y
PBL
(EKF-
cellbank)
n.a. 47,XX,+mar[26]/
46,XX[14]
FISH: min(18)(:p11.21q11.1:)
breakpoint
in 18p between clone RP11-794M8 (13.03MB) and RP11-411B10 (13.99MB)
cenM;
subcenM; BAC RP11-411B10
normal healthy young woman {0} provided by Drs. Wagner and Stibbe, Hannover, Germany  
  18-O-
p11.21/
1-4
female/
adult
PBL paternal 47,XX,+mar[80%]/
46,XX[20%]
mar(18)(:p11.21q11.1:)
size 1 MB
subcenM with 3 BACs, array-CGH Difficulty conceiving; patient’s father normal ; patient delivered a normal daughter with sSMC
{98} case 18
{171} case 18-2
 
  ***
18-O-
p11.21/
1-5
***
n.a./
prenatal
AF de novo 47,+mar[100%] mar(18)(:p11.21q11.1:)
size ~2.6MB = position 12.80 MB
subcenM with 3 BACs, array-CGH At 4 months normal (marker detected on amniocentesis for AMA {98} case 19  
  18-O-
p11.21/
1-6
female/
prenatal
AF n.a. 47,XX,+mar[40%]/
46,XX[60%]
mar(18)(:p11.21q11.1:)
FISH-data: RP11-151D11(13.08MB) on sSMC
in aCGH no euchromatin deteceted
cenM;
subcenM
Advanced maternal age; normal US, normal child born, normal at 1 y {149}  
  18-O-
p11.21/
2-1
n.a./
newborn
PBL paternal 49,+mar,+mar,+mar[?%]/
48,+mar,+mar[?%]/
47,+mar[?%]
mar(18)(:p11.1q11.1:)x2, mar(18)(:p11.21q11.1:) cenM;
subcenM
multiple malformations,
died at 7th day of life;
Father clinically normal.
{0} provided by Dr. Giorgio Paskulin, Brasil  
  ***
18-O-
p11.21/
3-1
***
female/
1y
PBL n.a. 47,XX,+mar[368]/
46,XX[123]
r(18)(::p11.21q11.2::)
FISH-data: breaks between RP11-431B10 / RP11-48I17; RP11-780G2 / RP11-198L17, i.e. 14,384,062 / 14,481,186 and 18,166,539 / 18,119,880
FISH using cep and BACS normal at 1 y and 34 m apart from hemivertebrae and rib anomalies {141}  
  18-O-
p11/
1-1
male/
prenatal
CH, AF, chord PBL de novo 47,XY,+mar/
46,XY
CH: mar in 18/26
AF: mar in 9/80
PBL. mar in 2/100
r(18)(::p11q11::) FISH with all available centromeric probes, wcp 18 CVS and AF due to advanced maternal age; normal child born at term
{70} case 9  
  18-O-
p11.1/
1-1
female/
prenatal
AF mat
(mar in 26%)
47,XX,+mar[?%]/
46,XX[?%]
Interphase: 65% of 200 cells
min(18)(:p11.1q11.1:)* FISH with centromeric probes normal child born; normal at 6m {110}  
  18-O-
p11.1/
2-1
female/
adult
PBL
(EKF-
cellbank)

n.a. 47,XX,+mar[16]/
46,XX[14]
min(18)(:p11.1q11.1~11.2:)
RP11-10G8 present on sSMC
cenM
subcenM
infertile female {0} provided by Reprogenet, Spain  
                     

 

O-Cases with similar imbalances NOT caused by sSMC (O-IMB):

 

 
  case no. gender/
age at diagnosis
studied
material
de novo/
inherited
GTG-banding result and FISH result incl. grade of mosaicism test
methods
clinical symptoms reference  
  18-O-
IMB-
pter/
mult
>20 patients with dup 18p and (almost) no symptoms {115} {100} 3 cases
{101}
{102} 2 cases
{103} 9 cases
{107} 1 case
{115}
 
  18-O-
IMB-
q11/
1-1
male or female/
postnatal
PBL familial ins(11;18)(p15;q11q21) 46,der(11)(11pter11p15::18q1118q21::11p1511qter) none see below {106}  
one carrier normal, two carriers slightly mentally retarded
  18-O-
IMB-
q11.2/
1-1
n.a./
prenatal
AF maternal ins(18)(p13.2q1.2q11.2) 46,der(18)(pterp11.32::q12.2q11.2::p11.32qter) MCB see below {105}  
normal at age of three months
                   


O-cases with unclear/insufficient characterization of the sSMC (CO):

 

 
  case no. gender/
age at diagnosis
studied
material
de novo/
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  18-
CO-1
female/
prenatal
AF/PBL de novo 47,XX,+mar[820]/
46,XX[180]
min(18) all available centromeric probes see below {23} case 2  
Amniocentesis due to advanced  maternal age; newborn with alcohol abuses syndrome (low weight, developmental delay, microcephaly, mitral stenosis)
  18-
CO-2
female/
28y
PBL n.a. 47,XX,+mar[2]/
46,XX[98]
r(18) all available centromeric probes Ring chr. detected due to transmission to clinically affected daughter with karyotype 46,XX,r(18) {29}  
  18-
CO-3
female/
11y
PBL de novo 47,XX,+mar[85%]/
46,XX[15%]
r(18) FISH with all available centromeric probes normal at age of 12y apart from eventually familial short stature {8} case 9  
  18-
CO-5
female/
prenatal
AF de novo 47,XX,+mar[6]/
46,XX[9]
mar(18) wcp 18? Advanced maternal age; normal sonography, normal at birth {86} case 66  
  18-
CO-6
female/
adult
PBL n.a. 47,XX,+mar[?%]/
46,XX[?%]
min(18) wcp 18? normal female; mar detected due to mar presence in unborn child. {86} mother of case 73  
  18-
CO-7
female/
36y
PBL n.a. 47,XY,t(17;18)(q11.1;q11.2), +mar mar(18)
karyotype balanced)
SKY normal female; repeated abortions {131}
{171} case 18-3
 
                     

 


References

Cases with iso-chromosome 18p (W-iso)

According to {32} i(18p) commonly form through meiosis II non-disjunction immediately followed by meiotic or early post-meiotic mitotic miss-division at the centromere; the i(18p) are preferentially of maternal origin. Exceptions are familial forms like described in {35, 37, 39, 43}.

 
  case no. reference  
  18-Wi-1 {3} case 3;  {32} case 6  
  18-Wi-2 to 18-Wi-3 {4} cases 22, 24; {5} cases 10-11  
  18-Wi-4 {6}; {5} case 8; {58} case 9  
  18-Wi-5 to 18-Wi-13 {7}; {8} case 11  
  18-Wi-14 {11} case 1  
  18-Wi-14 to 18-Wi-15 {13} case 12-13  
  18-Wi-16 {17}  
  18-Wi-18 {18} case 2  
  18-Wi-19 {19}  
  18-Wi-20 to 18-Wi-21 {20-21} cases 14-15  
  18-Wi-22 {20} case 16  
  18-Wi-23 to 18-Wi-24 {5} cases 9, 12; case 12 = {58} case 8  
  18-Wi-25 {24} case 2  
  18-Wi-26 {25} case 4  
  18-Wi-27 {28} case B  
  18-Wi-28 to 18-Wi-29 {30} cases 1-2  
  18-Wi-30 {31} case VII  
  18-Wi-31 to 18-Wi-39 {32} cases 1-5; 7-9  
  18-Wi-40 {34}  
  18-Wi-41 {35} i(18p) maternal in origin (mother normal with 2/50 metaphases in blood with sSMC)  
  18-Wi-42 {36} mosaic: 47,XY,+i(18p)/46,XY  
  18-Wi-43 {37} - 47,XX,del(18)(p11.21),+i(18p)  
  18-Wi-44 {38}  
  18-Wi-45 {39} - 47,XX,del(18)(p11),+i(18p)  
  18-Wi-46 {40}  
  18-Wi-47 {41}  
  18-Wi-48 {42} case 2  
  18-Wi-49 {43}  
  18-Wi-50 {44}  
  18-Wi-51 to 18-Wi-52 {45 cases 9-10, {78}  
  18-Wi-53 {46}  
  18-Wi-54 to 18-Wi-55 {47}  
  18-Wi-56 {48}  
  18-Wi-57 {49}  
  18-Wi-58 {50}  
  18-Wi-59 {51}  
  18-Wi-60 to 18-Wi-61 {52}  
  18-Wi-62 {53}  
  18-Wi-63 {54} = {58} case 4  
  18-Wi-64 {55}  
  18-Wi-65 {56}  
  18-Wi-66 to 18-Wi-77 {19} 12 cases reviewed but not detailed here with original citation  
  18-Wi-78 {57}  
  18-Wi-79 to 18-Wi-80 {58} cases 1 and 3 = {59} cases 4 and 2  
  18-Wi-81 to 18-Wi-84 {58} cases 2, 5, 6, 7  
  18-Wi-85 {60}  
  18-Wi-86 to 18-Wi-87 {61}  
  18-Wi-88 {62} mosaic karyotype with loss of one X-chromosome in a certain percentage of the cells  
  18-Wi-89 {63}  
  18-Wi-90 {64}  
  18-Wi-91 to 18-Wi-92 {65} cases 12-13  
  18-Wi-93 {67}  
  18-Wi-94 {69}case 4; inv dup 18p and inv dup 18q and normal 18  
  18-Wi-95 {71}  
  18-Wi-96 to 18-Wi-97 {72} 2 cases  
  18-Wi-98 to 18-Wi-99 {74} cases 19 and 23, {90} cases 24 and 29  
  18-Wi-100 {0} case provided by Dr. Küpferling, Cottbus, Germany  
  18-Wi-101 {76} 1 case of 15109 CVS cases  
  18-Wi-102 {128} case 9  
  18-Wi-103 {111} postnatal - case 26  
  18-Wi-104 {0} provided by Dr. Ivan Iourov, Moscow, Russian Federation  
  18-Wi-105 {79}  
  18-Wi-106 {80} 1case  
  18-Wi-107 to 18-Wi-117 {81} 11 cases  
  18-Wi-118 {82} case 2  
  18-Wi-119 to 18-Wi-123 {83} cases 12-16  
  18-Wi-124 to 18-Wi-128 {84} cases 17-21  
  18-Wi-129 {0} provided by Jasen Andersen, Brisbane, Australia  
  18-Wi-130 {0} provided by Dr. Deutinger, Vienna, Austria  
  18-Wi-131 {0} provided by Dr. Decker, Mainz, Germany  
  18-Wi-132 {156} case 19
 
  18-Wi-133 {85}  
  18-Wi-134 to 18-Wi-137 {86} cases 67-68; 72-73  
  18-Wi-138 {87} (EKF-cellbank)
 
  18-Wi-139 {158} case Si-3  (EKF-cellbank); array: pter-0.36MB of q-arm
 
  18-Wi-140 {89} case 3  
  18-Wi-141 {0}  provided by Dr. Tittelbach, Nürnberg, Germany  
  18-Wi-142 {111} postnatal - case 28  
  18-Wi-143 {156} case 18  
  18-Wi-144 {111} postnatal - case 27  
  18-Wi-145 to 18-Wi-146 {0} cases provided by Dr. Dilek Aktas, Ankara, Turkey  
  18-Wi-147 {111} postnatal - case 29  
  18-Wi-148 to 18-Wi-149 {113} postnatal - 2 cases  
  18-Wi-150 {128} case 10  
  18-Wi-151 to 18-Wi-153 {116} postnatal - 3 cases; mosaicism in buccal mucosa with normal cells  
  18-Wi-154 {117} prenatal - mosaicism  
  18-Wi-155 {119} case 3, prenatal  
  18-Wi-156 {124} postnatal; {139} case P-9  
  18-Wi-157 {120} postnatal - mos 47,XY,+i(18)/45,X  
  18-Wi-158 {121, 161} prenatal i(18p) present in 35% of the cells; postnatal no i(18p) detectable - normal child  
  18-Wi-158a {0} normal 27y old male - i(18p) in 100% of peripheral blood cells; provided by Dr. Baltaci, Ankara, Turkey  
  18-Wi-159 to 18-Wi-160 {122} postnatal - cases 5 and 6  
  18-Wi-161 to 18-Wi-163 {123} prenatal - 3 cases  
  18-Wi-164 {0} prenatal case provided by Dr. Junge, Dresden [47,XY,+mar[23]/46,XY[35]]  
  18-Wi-165 {0} prenatal case provided by Dr. Michael Petersen, Athens, Greece  
  18-Wi-166 {126} postnatal case  
  18-Wi-167 {127} postnatal case  
  18-Wi-168 {129; 182} 1/42 postnatal cases with mosaic (19% sSMC in blood, 68% in fibroblasts abdomen; 94% in fibroblasts forehead) {146}
 
  18-Wi-169 to 18-Wi-209 {129; 182} 41/42 postnatal cases without mosaic {146}
 
  18-Wi-210 {132} prenatal; mosaic with normal cell line  
  18-Wi-211 {133} postnatal  
  18-Wi-212 to 18-Wi-220 {134} postnatal - 9 cases  
  18-Wi-221 {135} postnatal  
  18-Wi-222 {136} postnatal  
  18-Wi-223 {137} postnatal  
  18-Wi-224 {138} postnatal  
  18-Wi-225 {142} postnatal  
  18-Wi-226 {143; 150} postnatal  
  18-Wi-227 to 18-Wi-228 {157} postnatal, provided by Dr.Maria Isabel Melaragno, Sao Paolo, Brazil
1 case asymmetric - array: 2x on sSMC: pter to 15.39; 1x on sSMC: 15.39 to 17.36
 
  18-Wi-227 {144} postnatal  
  18-Wi-228 {145} postnatal  
  18-Wi-229 {0} provided by Dr. Iourov, Moscow, Russia; postnatal  
  18-Wi-230 {0} provided by Dr. Iourov, Moscow, Russia; postnatal  
  18-Wi-231 {0} provided by Dr. Melaragno, Sao Paulo, Brasil; postnatal  
  18-Wi-232 {0} provided by Dr. Melaragno, Sao Paulo, Brasil; postnatal; break in 18q11.2; pos: 17.48 MB  
  18-Wi-233 {0} provided by Dr. Sheth , Ahmedahad , India; postnatal  
  18-Wi-234 {0} provided by Dr. Mulhatino, Rio de Janeiro, Brasil  
  18-Wi-235 to 18-Wi-250 {152} 16 cases  
  18-Wi-251 {153} postnatal  
  18-Wi-252 {155} postnatal  
  18-Wi-253 {0} prenatal; provided by Dr. Reiber, Jena, i(18)(q11.2); TOP  
  18-Wi-254 {0} 47,XY,+i(18)(q11.1)[4]/47,XY,+min(18)(:p11.1->q11.1:)15]/46,XY[21]; postnatal, provided by Dr. T. Martin, Homburg, Germany  
  18-Wi-255 {0} prenatal; provided by Agnieszka Gnys-Wiercioch, Ruda Slaska, Poland
 
  18-Wi-256 {159} prenatal, mosaic  
  18-Wi-257 to 18-Wi-258
{160} cases 17 and 19 - prenatal, mosaic - aCGH
 
  18-Wi-259 {162; 170} postnatal  
  18-Wi-260 to 18-Wi-263 {163} 4 cases  
  18-Wi-264 {163} complex case postnatal: 47,XY,+i(18)(p10)/47,XY,+der(18)t(18;21)(q21.1;q11.2)  
  18-Wi-265 {164} prenatal mosaic  
  18-Wi-266 {165} besides i(18p) also i(21p)  
  18-Wi-267 {0} postnatal; provided by Dr. F. Sheth, Ahmedabhad, India  
  18-Wi-268 {167}  
  18-Wi-269 {168} case 1  
  18-Wi-270 {0} postnatal; provided by Dr. Midyan, Yerevan, Armenia
 
  18-Wi-271 {0} prenatal; provided by Dr. Kania, Ruda Slaska, Poland
 
  18-Wi-272 {0} postnatal; mar only in 11%!!; slight DD; provided by Dr. Lagou, Athens, Greece
 
  18-Wi-273 {0} postnatal; provided by Dr. Baltaci, Ankara, Turkey  
  18-Wi-274 {172} prenatal  
  18-Wi-275 {173} postnatal  
  18-Wi-276 {174} postnatal  
  18-Wi-277 to 18-Wi-290 {176} 14 cases  
  18-Wi-291 {0} postnatal, provided by Dr. Weimer, Kiel, Germany  
  18-Wi-292 {0} postnatal, provided by Dr. Natiq, Rabat, Maroc
 
  18-Wi-293 {177} 1 prenatal mosaic case by NIPT  
  18-Wi-294 {178} 1 prenatal case (SNP-array) case 3  
  18-Wi-295 to 18-Wi-296 {178} 1 pre- and 1 postnatal case  
  18-Wi-297 {180} 1 case prenatal, mosaic30%  
  18-Wi-298 {0} postnatal, provided by Dr. Ruml, Serbia  
  18-Wi-299 {0} postnatal; provided by Dr. Ilic, Belgrade, Serbia
 
  18-Wi-300 {181} postnatal  
  18-Wi-301 to 306 {182} postnatal 6 cases  
  18-Wi-307 {183} prenatal  
  18-Wi-308 to 309 {184} prenatal (twins)  
       

 



Cases with clinical findings (W)

 

 
  case no. gender/
age at diagnosis
studied
material
de novo/
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  18-W-
pter
see 18-U-10    
  18-W-
p11.22/
1-1 °
male/
prenatal
AF n.a. 47,XY+mar[15]/
46,XY[5]
min(18)(:p11.22q11.1:)*
aCGH: 9.83-14.92 MB
array-CGH AMA, cerebral malformation; dysmorphic face {160} case 18  
 
***
18-W-

p11.21/
1-1
***
n.a./
postnatal
PBL n.
a.
47,+mar[68%]/
46[34%]
min(18)(:p11.21q11.2:)*
array: distal clone in 18p RP11-756J15 (13.17MB)
distal clone in 18q RP11-639E23 (19.34MB)
array-CGH developmental delay, dysmorphic features {91} case 11
{109} case 8
 
 
***
18-W-

p11.21/
1-2 °
***
male/
2.5y
PBL de novo 47,XY+mar[41]/
46,XY[9]
mar(18)(:p11.21q11.2:)
array: 12.60-19.51 MB (hg19)
equals in hg18: 12.59-17.76 MB
array-CGH (Illumina) speech delay, minor VSD, atopic eczema, anxiety {0} provided by Dr. Marie Trková, Praha, Czech Republic  
  18-W-
p11.21/
2-1 °
male/
49y
PBL n.a. 47,XY,+i(18p)[15] idic(18)(:p11.21q10:) cenM;
subcenM;
MCB
see below {75} case 18-4  
severe mental retardation, thin skin, hypogonadism, brachydactyly, long face, high palate, bilateral hearing loss; left hemiplagia (CVA 1992); developmental retardation - walking at 3 years; birth at term - 2800g
  18-W-
p11.21/
3-1 °
male/
30y
PBL/
BM
de novo 47,XY,+r[13]/
46,XY[42]
r(18)(::p11.21q10::)* all cep probes;
pericentric YAC clones as detailed in {66}
normal pregnancy and delivery; learning disabilities; multiple symptoms summarized as Klippel-Trenaunay syndrome {66}  
  18-W-
p11.1/
1-1
see 18-U-23    
  18-W-
p11.1/
2-1 °
female/
1m
PBL de novo 47,XX,+mar[15] min(18)(:p11.1q11.2:)
FISH: BAC in 17.43MB present
cenM;
subcenM;
MCB
child without visible clinical signs; hyperbilirubinemia; artrial septal defect; open ductus botalli {75} case 18-2  
  18-W-
p11.1/
2-2 °
male/
13y
PBL n.a. 47,XY,+mar[90%]/
46,XY[10%]
min(18)(:p11.1q11.2:)
FISH: BAC in 17.43MB present
array: 15.18-17.48
cenM;
subcenM;
midi; aCGH
see below {158} case Sm-8  
  child with 'abnormal behavior' (aggression and auto aggression) and small genitals. At birth head circumference at 3rd-10th, and weight at 3rd centile. At 13y OFC at 75-90 centile and obesity.  
  18-W-
p11.1/
2-3 °
female/
11m
PBL; fibroblasts n.a. 49,XX,+marx3[1]/ 48,XX,+marx2[2]/ 47,XX,+mar[25]/
46,XX[32]
no sSMC in skin fibroblasts
mar(18)(:p11.1q11.2:)
aCGH: size 3.4 MB
aCGH, cep 18 hydrops, renal impairment, talipes {148} case 7  
  18-W-
p11.1/
3-1
female/
13y
PBL de novo 47,XX,+mar[70%]/
46,XX[30%]
min(18)(:p11.1q11.1: :q12.3q21.1:)
orientation of fragments not clear
sSMC derived from a maternal normal chromosome 18
midi; UPD-test see below {27}  
born after normal pregnancy; weight: 3600g, length: 56cm (>90. centile); OFC 35cm (25.-50. centile); at 11y normal length and weight; but hypertelorism with inner and outer canthal distance (3.7cm, 9.8cm) >97th centile; bilateral epicantic folds, upward slanting palpebral fissures; short, upturned nose, long philtrum, short neck, widely spaced nipples, shirt 5th fingers, cubitus valgus, 3 hyperpigmented areas on abdomen. pubertal development at Tanner stage 3; IQ 76, hyperactive, suffers from dyslasia
  18-W-
p11.1/
4-1°
male/
24y
PBL de novo 47,XY,+mar[4]/
46,XX[26]
r(18)(::p11.1q11.2:
:p11.1
q11.2:
:p11.1
q11.2::)
array: 16.1-21.12MB
subcenM
array-CGH; UPD-test
see below {125}  
uncomplicated pregnancy of 37 weeks, weight at birth of 2670 grams with a single umbilical artery; in first week diagnosed: anal atresia, dysplastic lumbar and sacral vertebrae, penoscrotal hypospadia, cryptorchism on both sides, bifid scrotum, ureteral flow abnormality (dilatation of the higher urinary tract caused by vesico ureteral reflux, trabeculated bladder), radial dysplasia and thumb hypoplasia on the right upper extremity and preaxial polydactyly of the left hand. The diagnosis VACTERL-association was made, although there were no abnormalities of heart, trachea and esophagus. The urinary flow problems resulted in frequent infections and some episodes of urosepsis, finally causing chronic renal insufficiency. In his teens he underwent cholecystectomy because of an abnormal gallbladder full of stones. A pancreas fissum was seen. Neurologic investigation showed no signs of tethered cord syndrome. School performances were normal, there were no reasons for IQ testing. As an adult his height was on the 3rd centile and his headcircumference was normal.
  18-W-
p11.1/
5-1 °
male/
23y
PBL mat
(10% sSMC instead of normal #18)
47,XY,+mar[75]/
46,XX[25]
r(18)(::p11.1q21::) FISH with locusspec. probes see below {140}  
birth weight 2,250 g (<3rd centile), length 42 cm (<3rd centile). At 9 months hypotonia, motor retardation, microcephaly, (occipitofrontal circumference [OFC] 42 cm; <3rd centile), hypotelorism, depressed nasal bridge, underdeveloped alae nasi, very hypoplastic columella, smooth philtrum, deciduous single median maxillary central incisor, bilateral clinodactyly, cryptorchidism. length at the 10th centile (68 cm), weight at the 50th centile (8.5 kg). At 3 years developmental quotient of 70 and IQ 44 with autistic features at age 6 years. At 9 years add. short stature at 125 cm (<3rd centile), normal weight (21.5 kg; 10th centile), and microcephaly (OFC 49 cm; <3rd centile). He had a permanent single median maxillary central incisor, long cupped ears with large lobes, and short neck. Also small penis, cryptorchidism, flat feet, frontotemporal atrophy, and large cisterna magna, bifid pelvis on the left kidney; at age 17 years severe sleep apnea. At 23 years, he suffered from severe sleep apnea, obesity, and idiopathic leg edema treated with antidiuretics. Height 155 cm(<3rd centile) weight was 90 kg (>97th centile), cognitively impaired, but was well-mannered and very kooperative with a friendly attitude.
mother phenotypically normal except for a double ureter and bifid renal pelvis (as in son)
  18-W-
q12.2/
1-1 °
n.a./
postnatal
PBL n.a. 47 [100%] idic(18)(q12.2) array-CGH developmental delay {109} case 16  
                     

 

W-Cases with similar imbalances NOT caused by sSMC (W-IMB):

 

 
  case no. gender/
age at diagnosis
studied
material
de novo/
inherited
GTG-banding result and FISH result incl. grade of mosaicism test
methods
clinical symptoms reference  
  18-W-
IMB-
p11.32/
1-1
male/
11y
PBL n.a. 46,XY,dup(18)(p11.21p11.32),
inv(20)(p13q11)
10.2MB
array-CGH see below {114} case 71  
mild mental retardation, growth retardation, mild dysmorphic features, behavioural problems, hernial inguinalis, ADHD
  18-W-
IMB-
q11.2/
1-1
n.a./
postnatal
PBL n.a. 46,dup(18)(q11.2) n.a see below {96}  
knee dislocation and hyperpigmentation
  18-W-
IMB-
q11.2/
1-2
n.a./
postnatal
PBL n.a. 46,dup(18)(q11.2) n.a see below {105}  
knee dislocation and hyperpigmentation
                   


W-cases with unclear/insufficient characterization of the sSMC (CW):

 

 
  case no. gender/
age at diagnosis
studied
material
de novo/
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  18-
CW-1
male/
23y
PBL n.a. 47,XY,+mar r(18) SKY Klippel-Trenaunay-Weber syndrome {14} case 6  
  18-
CW-2
male or female/
various
PBL familial 47,+mar der(18)t(18;21 or 22) n.a. mental retardation, and different dysmorphic features as described in detail by the authors {10; 166}  
  18-
CW-3
male/
prenatal
AF de novo 47,XY,+r[28%]/
46,XY[72%]
r(18) FISH with all available centromeric probes pregnancy terminated; autopsy showed 2 vessels in umbilical cord; abnormal left kidney. {12} case 10  
  18-
CW-4
female/
postnatal
PBL n.a. 47,XX,+mar[mosaic status unclear] dic(18) Primed in situ hybridization (PRINS) dysmorphic features like brachycephaly, short upper jaw, missing ear-lobe, micrognathia {16}  
  18-
CW-5
female/
1d
Fibroblasts de novo 47,XX,+mar[15%]/
46,XX[85%]
mar(18) FISH with all available centromeric probes see below {22} case 33  
Baby was delivered at term but died one day after birth; abnormal facial appearance, abnormal position of the limbs, ventricular septal defect, non-mmunological hydrops fetalis 
  18-
CW-6
n.a./
n.a.
n.a. n.a. 47,+mar[?%] mar(18) FISH with ? developmental abnormal {73} 1 case  
  18-
CW-7
female/
8m
PBL de novo 47,XX,+mar[30%]/
46,XX[70%]
mar(18) PRINS see below {73} case 3  
developmental delay, weight at 5th centile, lenght at 10. centile, OFC at 5th centile at 8m. mild hypotonia, flat nasal bridge, high arched palate, protruding tongue, capillary hemangiomas on the left upper eyelid, lower lip, right side of the back, right upper chest, right second finger, and left fifth finger; patent ductus arteriosus.
  18-
CW-8
male/
newborn
PBL. de novo 47,XY+del(18)(q11)[100%]
mar looks like an i(18p!!)
n.a. no FISH developmental abnormal {92}  
  18-
CW-9
male/
newborn
PBL. de novo 47,XY,+del(18)(q11)[100%] n.a. no FISH developmental abnormal {93}  
  18-
CW-10
male/
newborn
PBL. de novo 47,XY,+del(18)(q11)[100%] n.a. no FISH developmental abnormal {93}  
  18-
CW-4
n.a./
prenatal
AF de novo 47,+mar[17%]/
46[83%]
mar(18) wcp18; cep18 Abnormal triple test, sonographic malformations (facial dysmorphism), TOP; Fetopathology low set ears, retrognathism {119} case 8  
                     

 

 


References

Cases with unclear clinical correlation (U)

 

 
  case no. gender/
age at diagnosis
studied
material
de novo/
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  18-
U-1
male/
prenatal
AF de novo 47,XY,+mar[11]/
46,XY[11]
i(10)(:p11.1q11.1:
:p
. or. q11.1q11.1 or p11.1)[15]/
i(10)(pter
q11.21: :q11.21pter) x2 (tetraploidmitosis)[2]/
min(18)(p11.1
q11.1)[3]
cenM;
subcenM
singularly umbilical cord artery, complex heart defect and microcephalus detected in ultrasound; fetus spontaneously aborted {1} case 35  
  18-
U-2
male/
postnatal
PBL de novo 47,XY,+mar[100%?] min(18)(:p11.2 or p11.1q11.2) midi n.a. {15} case 6  
  18-
U-3
see mult 2-12
{20; 21} case 20  
  18-
U-4
female/
7y
PBL de novo 47,XX,add(18)(p11.2),+r[5]/
46,XX,add(18)(p11.2)[11]
inv dup(18)(qter→p11.32::
q21.3qter),+r(18)(p11.32q21.3)
FISH with different YAC probes as specified in {27} see below {27} case 6  
Born after uncomplicated pregnancy. Apgar score 8 at 1 min. Transient feeding difficulties in neonatal period. No growth delay during early months of life. Developmental milestones moderately retarded. At 7y short stature, mental retardation, and multiple dysmorphic features.
  18-
U-5
female/
10y
PBL de novo 47,XX,add(18)(p11.32),+r[40]/
46,XX,add(18)(p11.32)[60]
invdup(18)(qter→p11.32:
:p11.32p11.1::q21.3qter),+r(18)(p11.32q21.3)
FISH with different YAC probes as specified in {27} see below {27} case 7  
Psychomotor retardation at since1y; Apgar score 5 at 1 min. During first 2 months lack of sucking reflex and frequent vomiting; needed gastric tube feeding; convergent strabismus. Clinical examination revealed multiple minor anomalies
  18-
U-6
female/
11y
PBL de novo 47,XX,r(18)(p11.3q23), +r[112]/
46,XX,r(18)(p11.3q23)[88]
r(18)(p11.22q12.2) midi see below {33}  
unremarkable pregnancy, birth weight 3.1kg (25.-50. centile); facial dysmorphism and right club foot noted at birth; initially hyperactive, mild developmental delay, at 11y height at 10. centile, weight at 25. centile, OFC slightly below 50. centile; broad forehead, thick flaring eyebrows with mild synophrys, hypertelorism, upslanting palpebral fissures, bulbous tip of the nose, short philtrum, widely spaced nipples, bilateral clinodactyly of little fingers. 
  18-
U-7
male/
prenatal
n.a. n.a. 47,XY,+mar[mosaic] mar(18) SKY n.a.; termination of pregnancy {68}  
  18-
U-8
male/
prenatal
AF de novo 47,XY,-18,+mar1,
+mar2[100%]
fis(18)(:p11.21p10:)
fis(18)(:q10
q21.31:)
both ring chromosomes
diff. FISH probes n.a. {69} case 2  
  18-
U-9
see mult 2-18
{94} case MK
{95} case 15
 
  18-
U-10
male/
prenatal
AF
(EKF-
cellbank)
maternal 47,XY,+mar[100%] der(18)t(8;18)(p23.2~23.1;q11.1)
array: 8pter to 6,359,643 MB and 18pter to 17,112,922 MB
all wcp probes, subcenM, MCB, flow sorting, subtel 8p see below {95} case 10
{108} case 13
{158} case Sc-2
{166}
 
Third child of not consanguineous couple; the pregnancy was complicated by hyperemesis gravidarum treated with metoclopramid and there was a mild exposure to tobacco (3 cigarettes a day) and to alcohol (1 unit per month). No abnormalities noted prenatally; at birth weight and OFC at 10th centile and length at 50-90 centile but no apparent congenital abnormalities were found. At 1y failure to thrive and markedly psychomotor development delay (Griffith General Intelligence Quotient of 63). Neurological examination revealed slight muscular hypotonia but otherwise no abnormalities. MRI of the brain was normal. Laboratory analyses were unsuggestive for any metabolic disorder.  The mother was treated for attention-deficit/hyperactivity problems during her adolescence and her IQ seems to be borderline.
  18-
U-11
to 12
female and male/
prenatal
AF de novo 47,XX,+mar[7]/
46,XX[8]
and
47,XY,+mar[7]/
46,XY[13]
mar(18) diff. FISH probes Advanced maternal age or parental anxiety; TOP in both cases {86} cases 69-70  
  18-
U-13
male/
prenatal
AF de novo 47,XY,+mar1[7]/
47,XY,+mar2[4]/
46,XY[4]
mar(18), mar(18) diff. FISH probes Advanced maternal age; TOP in both cases {86} case 110  
  18-
U-14
to 15
n.a./
prenatal
AF n.a. 47,+mar[?%] mar(18) SKY no info available {97} 2 new cases  
  18-
U-16
female/
prenatal
AF n.a. 47,XX,+mar[100%] r(18)(::p11.21
q12.1::)
array: 11.19-23.60
cenM, subcenM,
array-CGH
advanced maternal age; hyperechogenic bowel, borderline ventriulomegaly; TOP {0} provided by Gordana Joksić, Belgrad, Serbia  
  18-
U-17
 to 20
n.a./
n.a.
n.a. n.a. 47,+mar[?%] mar(18) wcp probes no info available {112} 4 cases  
  18-
U-21
male/
prenatal
AF n.a. 47,XY,+mar[67%]/
46,XY[33%]
r(18)(::p11.1
q11.2::)[7]/
min(18)(:p11.1
q11.2:)[8]
cep probes; subcenM advanced maternal age;, no info available {0} provided by Dr. Junge, Dresden, Germany  
  18-
U-22
female/
prenatal
AF n.a. 47,XX,+mar[30%]/
46,XX[70%]
min(18)(:p11.1
q11.1~11.2:)
cep probes; subcenM advanced maternal age;couple opted for TOP, fetus normal by visual inspection; no autopsy performed. {0} provided by Dr. Nehama Israel  
  18-
U-23
male/
prenatal
AF de novo 47,XY,+mar[15] min(18)(:p11.1q11.1:) cenM;
subcenM; UPD-test
Amniocentesis due to advanced maternal age; hygroma colli detected in ultrasound, pregnancy terminated {1} case 26
{2} case 1
 
  18-
U-24
female/
newborn
PBL de novo 47,XX,+mar[22]/
46,XX[8]
der(18)t(2;18)(p23.1;q11.1) array-CGH see below {130; 166}  
IUGR; OFC >90th centile due to scalp edema, OFC became afterwards 10.-25. centile; dysmporphic features, congenital heart defect; at 7 m: growth retardation; weight <3rd centile, developmental delay; mentally retarded
  18-
U-25
female/
prenatal
AF n.a. 47,XX,+mar[?%]/
46,XX[?%]
min(18)(:p11.1q11.1:) ceps;
subcenM
no info available {0} provided by Dr. Vehbi Koc Vakfi, Istanbul, Turkey  
  18-
U-26
female/
prenatal
chord blood n.a. 47,XX,+mar[95%]/
46,XX[5?%]
min(18)(:p11.1q11.1:) ceps;
subcenM
no info available {0} provided by Dr. Wegener, Berlin, Germany  
  18-
U-27
female/
1y
PBL de novo 47,XX,+mar[100%] min(18)(:p11.1q11.1:)* different FISH-probes; array-CGH see below {46} case 10  
global developmental delay, occipital encephalocele, severe cerebellar hypoplasia, mild pontine and brainstem hypoplasia, a bicuspid aortic valve, atent ductus arteriosus, a duplicated left kidney
  18-
U-28
female/
prenatal
AF n.a. 47,XX,+mar[8]/
46,XX[7]
mar(18) SKY no info available {151} case F077572  
  18-
U-29
n.a./
prenatal
AF/ PBL de novo 47,XX,+18[5%]/
47,XY,+mar[50%]/
46,XX[45%]
mar(18) QF-PCR no info available apart from the fact that child is born
{154}  
  18-
U-30
male/
20y
PBL n.a. 47,XY,+mar[65%]/
46,XY[25%]
47,XY,+r(18)(::p11.21q11.1::)[10]/
47,XY,+r(18)(::q11.1
p11.21::p11.21q11.1::)[5]/
47,XY,+der(18)(:p11.21
q11.1:)[2]/
47,XY,+der(18)(:q11.1
p11.21::p11.21q11.1:)[2]/
46,XY[7]
cenM, subcenM DD in childhood {0} provided by Dr. Schulze, Hannover, Germany  
  18-
U-31
male/
prenatal
AF n.a. 47,XY,+mar[20] min(18)(:p11.21q11.2:)
array: 14.74-19.47
aCGH AMA, TOP {160} case 23  
  18-
U-32
female/
prenatal
AF de novo 47,XX,+mar[46%]/
46,XX[54%]
min(18)(:p11.1q11.2:)
array: 17.23-17.65
aCGH AMA, n.a. {169}  
  18-
U-33
male/
prenatal
chorion n.a. 47,XY,+mar[17]/
46,XX[3]
del(18)(q21.2:)
array: ~26Mb
aCGH AMA, normal baby born; no sSMC detected {180} 1 case  
  18-
U-34
male/
prenatal
AF n.a. 47,XY,+mar[30%]/
46,XY[70%]
min(18)(:p11.1q11.1:) cep; subcenM AMA; n.a. {0} provided by Dr. Mehnert, Neu-Ulm, Germany  
                     

 


References

Cases with neocentromeres (N)

 

 
  case no. gender/
age at diagnosis
studied 
material
de novo/
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  18-N-
mar/1
male/
1y
PBL de novo 47,XY,+mar[64]/
46,XY[36]
der(18). ish D18Z1-; wcp18+ different FISH probes (D15Z1; wcp15) see below {3} case 4; {99}  
born with cesarean section; weight 2600g; length 51cm; mild mental retardation; cardiovascular abnormalities VSD; mild valvular pulmonic stenosis, imperforate anus, dysplastic kidney; dysmorphic features, microtia; conductive hearing loss; brain with generalized dilation of ventricles; at age of 16 height of 180 cm
18-N-
qt22.1/1-1
male/
preantal
AF de novo 47,XY,+mar[100%] inv dup(18)(qterq22.1:
:q22.1
qter)
different FISH probes (BACs, SKY)
AMA, nasal bone hypoplasia, TOP; in autopsy no external dysm. signs {175}
                     

 

N-Cases with similar imbalances NOT caused by sSMC (N-IMB):

 

 
  case no. gender/
age at diagnosis
studied
material
de novo/
inherited
GTG-banding result and FISH result incl. grade of mosaicism test
methods
clinical symptoms reference  
  18-N-
IMB-
pter/
1-1 to
mult
16 cases with trisomy 18p

Review >20 patients with dup 18p and (almost) no symptoms {115}

{100} 3 cases
{101}
{102} 2 cases
{103} 9 cases
{107} 1 case
{115}
 
  18-N-
IMB-
qter/
1-1 to
mult
see {118} {118}