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

- sSMC -

CHROMOSOME 12

References

 

 

             
  Cases without
clinical findings
11 Cases with
clinical findings
16 symptoms  
  similar imbalances - no clinical findings similar imbalances with clinical findings  
    Cases with
isochromosome 12p
600    
  Cases with
unclear clinical correlation
Cases with
neocentromeres
5 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 12
mat
UPD 12
pat
UPD 12
unclear
 
           

PATIENTINFORMATION for sSMC(12)


the probably non-dosage sensitive pericentric region of chromosome 12


SCHEMATIC CYTOGENETIC DEPICTION

tl_files/tiny_templates/Bilder TL/sSMC/sSMC-12.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 ? ---28.47 uncritical region [33.20 centromere 36.50] uncritical region 39.90 --- 40.20 critical region

Below adapted for UCSC hg19, 2009

critical region ? --- 28.57 uncritical region [33.30 centromere 38.20] uncritical region 41.65 --- 42.00 critical region

 


Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

12p - proximal 12q - proximal
symptoms
autism 0 % (33 %)
developmental delay (50 %) (100 %)
dysmorphic face (100 %) (100 %)
growth retardation (50 %) (67 %)
heart defect (0 %) (33 %)
hypotonia (100 %) (0 %)
mental retardation (50 %) (33 %)
obesity (50 %) (0 %)
vision impaired (nystagmus) (100 %) (0 %)
number of cases (marked with “°” below) 2 3
 

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  
  12-O-
p12.2~
12.1/
1-1
male/
45y
PBL n.a. 47,XY,+mar[66%]/
46,XY[34%]
min(12)(:p12.2~12.1q10:)
FISH-data: RP11-517B23 at 31.4MB on sSMC
midi, subcenM, MCB ICSI-patient, normal with prognathia {150} case 17
{250} case 12-1
 
  12-O-
p11.22/
1-1
female/
36y
PBL
(EKF-
cellbank)
n.a. 47,XX,+mar[15]/
46,XX[3]
min(12)(:p11.22q11:) cenM,
subcenM
normal female, studied due to OAT syndrome of partner {250} case 12-2  
  ***
12-O-
p11.2/
1-1
***
female/
prenatal
AF/
PBL
de novo 47,XX,+mar[11]/
46,XX[9]
PBL (postnatal): mar in 7/10 cells
r(12) (::p11.2q11::)
RP11-847A19, RP11-133R2 (28.47MB) and RP118P13 (32.94MB) present on sSMC
array CGH, cep 12 AF due to abnormal MS-AFP; at 6m normal development {143} case 2
{186} case 4
 
  12-O-
p11.2/
2-1
male/
34y
PBL
(EKF-
cellbank)
n.a. 47,XY,+mar[3]/
46,XY[27]
min(12)(:p11.2q11:) cenM/ subcenM normal male, infertile {250} case 12-3  
  12-O-
p11.21/
1-1
male/
prenatal
AF n.a. 47,XY,+mar[3]/
46,XY[17]
r(12)(::p11.21q11::)
FISH-data: RP11-517B23 at 31.4MB on sSMC
midi, subcenM, MCB; UPD-test advanced maternal age, at birth normal child {0} provided by Dr. Hickmann, Düsseldorf, Germany  
  12-O-
p11/
1-1
female/
prenatal
AF de novo 47,XX,+mar[16]/
46,XX[14]
min(12)(:p11q11:)
maternal UPD 12
cenM;
long and short arm specific probes for 12p and 12q; UPD-test
see below {2}
{4} case 11
{237}
 
Amniocentesis due to advanced  maternal age; born after 39 weeks of gestation; Birth weight 2850g, length 46cm, head circumference 34cm, all around the 50th centile. Apgar score 9 , 10, 10. No congenital anomalies or dysmorphic features were noted. At age of six weeks, clinical examination indicated normal somatic and psychomotor development.
  ***
12-O-
p11.1/
1-1
***
male/
prenatal
 AF paternal
25% in PBL
47,XY,+mar[23]/
46,XY[7]
min(12)(:p11.1q12:)
FISH-dat
a: RP11-498B21 at 39.9MB on sSMC
cenM
subcenM
AF due to advanced maternal age, father with same marker normal {0} provided by Dr. Hickmann, Düsseldorf, Germany  
  ***
12-O-
p11.1/
2-1
***
female/
adult
PBL n.a. 47,XX,+mar[50%]/
46,XY[50%]
min(12)(:p11.1q12:)
CGH-data: 34.03 to 40.84MB - FISH confirmed 39.5 MB
cenM;
subcenM;
aCGH
normal female; sSMC inherited to developmentally delayed son (9y) - he has sSMC in 100% of PBL and 80% of bucchal muccosa {0} provided by Dr. Ovensräder, München, Germany  
  12-O-
p11.1/
3-1
male/
prenatal
AF maternal 47,XY,+mar[17]/
46,XY[23]
min(12)(:p11.1q11:) cenM
subcenM
AF due to advanced maternal age, mother normal {0} provided by Dr. Prager, Dresden, Germany  
                     

 

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

none reported yet

 

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  
  12-
CO-1
female/
prenatal
AF/PBL
cell line at ECACC DD0085
de novo 47,XX,+mar[3%-90%]/
46,XX
(mar in 38% of PBL)
min(12) all centromeric probes; wcp 12; UPD-test Amniocentesis due to advanced maternal gae; clinically normal after birth and at 7m {5} case 9
{12} case 3
 
  12-
CO-2
female/
adult
AF
cell line at ECACC DD1188
n.a. 47,XX,+mar[15]/
46,XX[15]
min(12) .ish(cep12+; wcp12-) all centromeric probes; wcp 12 clinically normal mother; same mar in child which died shortly after birth {11}
case6
 
                     

 


References

Cases with iso-chromosome 12p (W-iso)
i.e. Pallister-Killian-Syndrome (PKS)

 

 
  case no.  prenatal/ postnatal reference  
  12-Wpks-1 postnatal {17, 237} mild phenotype - mosaic  
  12-Wpks1a 5 years {247}  
  12-Wpks-2 postnatal {18}  
  12-Wpks-3 postnatal {19}  
  12-Wpks-4 postnatal {20} here a mosaic of i(12p) and min(12); - i(12p) of maternal origin  
  12-Wpks-5 prenatal {188} case 12-Wpks-5  
  12-Wpks-6 postnatal {163} 1 case  
  12-Wpks-7 to 12-Wpks-8 1 x prenatal, 1 x postnatal {21} - 1 case i(12p) of paternal origin  
  12-Wpks-9 postnatal {22}  
  12-Wpks-10 postnatal {23}  
  12-Wpks-11 postnatal {24} - i(12p) of paternal origin  
  12-Wpks-12 postnatal {25}  
  12-Wpks-13 prenatal {26}  
  12-Wpks-14 postnatal {27}  
  12-Wpks-15 postnatal {28}  
  12-Wpks-16 postnatal {29}  
  12-Wpks-17 prenatal {30}  
  12-Wpks-18 postnatal {31}  
  12-Wpks-19 postnatal {32}  
  12-Wpks-20 to 12-Wpks-22 3 x postnatal {33} - 3 cases of i(12p) of maternal origin  
  12-Wpks-23 postnatal {35} - i(12p) of paternal origin  
  12-Wpks-24 to 12-Wpks-42 11 x prenatal; 8 x postnatal {36} {37}? - 2 cases i(12p) of maternal origin, one case of paternal origin  
  12-Wpks-43 prenatal {38} - i(12p) of maternal origin  
  12-Wpks-44 prenatal {39}  
  12-Wpks-45 to 12-Wpks-46 2 x prenatal {40}  
  12-Wpks-47 prenatal {41} case with two PKS-chromosomes  
  12-Wpks-47a postnatal {248} case with two
PKS-chromosomes
 
  12-Wpks-48 to 12-Wpks-49 2 x postnatal {42}  
  12-Wpks-50 postnatal {43}  
  12-Wpks-51 postnatal {44}  
  12-Wpks-52 prenatal {45}  
  12-Wpks-53 prenatal {46}  
  12-Wpks-54 prenatal {47}  
  12-Wpks-55 postnatal {48}  
  12-Wpks-56 postnatal {49}  
  12-Wpks-57 postnatal {50}  
  12-Wpks-58 postnatal {51}  
  12-Wpks-59 prenatal {52}  
  12-Wpks-60 prenatal {53}  
  12-Wpks-61 postnatal {54}  
  12-Wpks-62 prenatal {55}  
  12-Wpks-63 postnatal {56}  
  12-Wpks-64 prenatal {57}  
  12-Wpks-65 to 12-Wpks-68 4 x postnatal {58}  
  12-Wpks-69 prenatal {62}  
  12-Wpks-70 postnatal {63}  
  12-Wpks-71 postnatal {64}  
  12-Wpks-72 prenatal {65}  
  12-Wpks-73 prenatal {66}  
  12-Wpks-74 postnatal {67}  
  12-Wpks-75 prenatal {68}  
  12-Wpks-76 postnatal {69}  
  12-Wpks-77 postnatal {70}  
  12-Wpks-78 postnatal {71}  
  12-Wpks-79 postnatal {72} = case 1 {93}  
  12-Wpks-80 prenatal {73}  
  12-Wpks-81 postnatal {74}  
  12-Wpks-82 prenatal {75}  
  12-Wpks-83 postnatal {76}  
  12-Wpks-84 to 12-Wpks-85 2 x postnatal {77}  
  12-Wpks-86 to 12-Wpks-87 2 x postnatal {78}  
  12-Wpks-88 to 12-Wpks-89 2 x postnatal {79}  
  12-Wpks-90 to 12-Wpks-92 1 x prenatal; 2 x postnatal {80}  
  12-Wpks-93 to 12-Wpks-99 7 x postnatal {81}  
  12-Wpks-100 to 12-Wpks-106 7 x prenatal {14}  
  12-Wpks-107 prenatal {82}  
  12-Wpks-108 to 12-Wpks-111 1 x prenatal; 2 x postnatal {83}  
  12-Wpks-112 postnatal {84}  
  12-Wpks-113 postnatal {85}  
  12-Wpks-114 to 12-Wpks-124 11 x postnatal {86}; case 1 = {87}  
  12-Wpks-125 prenatal {88}  
  12-Wpks-126 to 12-Wpks-127 2 x prenatal {89}  
  12-Wpks-128 to 12-Wpks-129 2 x prenatal {90}  
  12-Wpks-130 prenatal {91}  
  12-Wpks-131 prenatal {92}  
  12-Wpks-132 to 12-Wpks-135 1x prenatal, 3 x postnatal {93}  
  12-Wpks-136 prenatal {94}  
  12-Wpks-137 postnatal {95}  
  12-Wpks-138 postnatal {96}  
  12-Wpks-139 prenatal {97}  
  12-Wpks-140 postnatal {98}  
  12-Wpks-141 postnatal {99}  
  12-Wpks-142 prenatal {100}  
  12-Wpks-143 to 12-Wpks-145 1 x prenatal, 2x postnatal {101}  
  12-Wpks-146 to 12-Wpks-147 2 x prenatal {102}  
  12-Wpks-148 prenatal {104}  
  12-Wpks-149 to 12-Wpks-150 2 x postnatal {105} - 1 case i(12p) of maternal origin, 3 cases i(12p) of paternal origin  
  12-Wpks-151 postnatal {106}  
  12-Wpks-152 to 12-Wpks-153 2 x prenatal {108} cases 9 and 10  
  12-Wpks-154 prenatal {109}  
  12-Wpks-155 postnatal {111}  
  12-Wpks-156 prenatal {112} case 12  
  12-Wpks-157 prenatal {113}1 case  
  12-Wpks-158 postnatal {115} 1 case  
  12-Wpks-159 prenatal {116} 1 case - mosaic 47,XX,+12/47,XX,i(12p) mat UPD of normal chrs. 12  
  12-Wpks-160 prenatal {120} 1 case, {181}case 4  
  12-Wpks-161 postnatal {121} 1 case ; {161}  
  12-Wpks-162 postnatal {122} 1 case paternally derived mar  
  12-Wpks-163 prenatal {124} case 5  
  12-Wpks-164 postnatal {126} 1 case  
  12-Wpks-165 prenatal {128} case 19, {134} 1 case  
  12-Wpks-166 prenatal {188} case 12-Wpks-166  
  12-Wpks-167 prenatal {188} case 12-Wpks-167; Array: 0.00-36.29 MB  
  12-Wpks-168 to 12-Wpks-169 2 x prenatal {129} 2 cases  
  12-Wpks-170 to 12-Wpks-172 3 x prenatal {130} cases 62-65  
  12-Wpks-173 prenatal {188} case 12-Wpks-173  
  12-Wpks-174 postnatal {132; 179} 1 case - mosaic of tetrasomy, trisomy and disomy 12p  
  12-Wpks-175 to 12-Wpks-176 2 x prenatal {133}  
  12-Wpks-177 to 12-Wpks-183 7 x postnatal {134} 5 mat origin, 1 pat origin, 1 n.d.; {137}  
  12-Wpks-183 to 12-Wpks-184 2 x prenatal {134} 2 cases  
  12-Wpks-185 prenatal {181} case 5, {188} case 12-Wpks-185  
  12-Wpks-186 postnatal {138}  
  12-Wpks-187 prenatal {139}  
  12-Wpks-188 prenatal {145} 1 pat origin  
  12-Wpks-189 postnatal {151} 1 case  
  12-Wpks-190 to 12-Wpks-191 2 x prenatal {152} 2 cases  
  12-Wpks-192 prenatal {153} 1 case  
  12-Wpks-193 prenatal {154} 1 case  
  12-Wpks-194 to 12-Wpks-195 2 x prenatal {155} 2 cases  
  12-Wpks-196 postnatal {156} 1 case  
  12-Wpks-197 postnatal {157} 1 case  
  12-Wpks-198 prenatal {180}  
  12-Wpks-199 postnatal {159} 1 case  
  12-Wpks-200 postnatal {160} 1 case; {200} case 1  
  12-Wpks-201 to 12-Wpks-202 1 x prenatal, 1 x postnatal {162} 1 case  
  12-Wpks-203 prenatal {164} 1 case  
  12-Wpks-204 postnatal {165} 1 case  
  12-Wpks-205 to 12-Wpks-206 2 x postnatal {166} 2 cases  
  12-Wpks-207 to 12-Wpks-210 4 x postnatal {167} 4 cases  
  12-Wpks-211 prenatal {168} 1 case  
  12-Wpks-212 postnatal {169} 1 case  
  12-Wpks-213 postnatal {167} 1 case, {171}  
  12-Wpks-214 postnatal {172} 1 case  
  12-Wpks-215 postnatal {173} 1 case  
  12-Wpks-216 postnatal {174} case 19  
  12-Wpks-217 prenatal {175} 1 case  
  12-Wpks-218 prenatal {176} 1 case  
  12-Wpks-219 prenatal {177} 1 case  
  12-Wpks-220 postnatal {103} 1 case  
  12-Wpks-221 prenatal {178} 1 case  
  12-Wpks-222 prenatal {34} 3 cases  
  12-Wpks-223 postnatal {59}  
  12-Wpks-224 prenatal {60}  
  12-Wpks-225 prenatal {61}  
  12-Wpks-226 postnatal {184}  
  12-Wpks-227 to 12-Wpks-228 prenatal {185} cases 4 and 5  
  12-Wpks-229 postnatal {187} double ring!  
  12-Wpks-229a prenatal {236} double ring!  
  12-Wpks-230 to 12-Wpks-231 postnatal {189, 270} 2 cases  
  12-Wpks-232 to 12-Wpks-234 prenatal {190} 3 cases  
  12-Wpks-235 postnatal {191, 193} 1 case  
  12-Wpks-236 to 12-Wpks-242 prenatal {192} 7 cases  
  12-Wpks-243 postnatal {194} case 25838  
  12-Wpks-244 postnatal {195}  
  12-Wpks-245 prenatal {0} case provided by Dr. Morlot, Hannover  
  12-Wpks-246 to 12-Wpks-247 prenatal {196} cases 4 and 5, 1 mosaic  
  12-Wpks-248 to 12-Wpks-249 postnatal {197} 2 cases  
  12-Wpks-250 prenatal {198}  
  12-Wpks-251 postnatal {199} 48,XX,+i(12p)x2[2]/46,XX[8]  
  12-Wpks-252 to 12-Wpks-258 postnatal {200} 7 cases  
  12-Wpks-259 prenatal {201}  
  12-Wpks-260 prenatal {202}  
  12-Wpks-261 to 12-Wpks-262 postnatal {203} 2 cases  
  12-Wpks-263 prenatal {204; 205}  
  12-Wpks-264 prenatal {206}  
  12-Wpks-265 prenatal {207}  
  12-Wpks-266 prenatal {208}  
  12-Wpks-267 postnatal {209; 210} besides sSMC also XXY and del(1)(p36.1p36.3)  
  12-Wpks-268 to 12-Wpks-270 postnatal {211} 3 cases  
  12-Wpks-271 postnatal {212} case 3  
  12-Wpks-272 to 12-Wpks-327 postnatal {213; 229; 232; 234} 58 cases
{230} 15 of those cases
 
  12-Wpks-328 to 12-Wpks-329 postnatal
most likely small mosaic; mild symptoms only
{231} 2 cases  
  12-Wpks-330 prenatal {0} provided by Dr. Morlot, Hannover, Germany  
  12-Wpks-331 prenatal {0} provided by Dr. Mau-Holzmann, Tübingen, Germany  
  12-Wpks-332 prenatal {0} provided by Dr. Petersen, Athens, Greece  
  12-Wpks-333 postnatal {214}  
  12-Wpks-334 postnatal {215}  
  12-Wpks-335 postnatal {216}  
  12-Wpks-336 prenatal {217}  
  12-Wpks-337 postnatal {218}  
  12-Wpks-338 prenatal {0} provided by Dr. Morlot, Hannover, Germany  
  12-Wpks-339 postnatal {219}  
  12-Wpks-340 postnatal {220} - i(12p) of maternal origin  
  12-Wpks-341 prenatal {0} provided by Dr. Morlot, Hannover, Germany  
  12-Wpks-341 to 12-Wpks-354 postnatal {222} 13 cases  
  12-Wpks-355 prenatal; also der(15)t(15;18)(q24;q21)mat {223}  
  12-Wpks-356 postnatal {224}  
  12-Wpks-357a postnatal twin II {225}  
  12-Wpks-357b postnatal twin I {225, 237}  
  12-Wpks-358 to 12-Wpks-360 postnatal {226} 3 cases  
  12-Wpks-361 to 12-Wpks-365 postnatal {227; 233} 5 cases  
  12-Wpks-366 prenatal {0} provided by Dr. Manolakis, Athens, Greece  
  12-Wpks-367 postnatal {229}  
  12-Wpks-368 postnatal {238} 2 isochromosomes in 47% of skin fibroblasts  
  12-Wpks-369 to 12-Wpks-371 postnatal {239} 3 cases  
  12-Wpks-372 postnatal {0} provided by Dr. A. Kuechler, Essen, Germany  
  12-Wpks-373 postnatal {242}  
  12-Wpks-374 prenatal {243}  
  12-Wpks-375 to 12-Wpks-464 postnatal {244} 90 cases  
  12-Wpks-465 to 12Wpks-467 postnatal {245}  
  12-Wpks-468 postnatal {246}  
  12-Wpks-469 postnatal {247}  
  12-Wpks-470 to 12-Wpks-477 postnatal {249}  
  12-Wpks-478 to 12-Wpks-489 postnatal {251} 2 female, 10 male  
  12-Wpks-490 prenatal {0} provided by Dr. Eiben, Essen, Germany  
  12-Wpks-491 prenatal {252}  
  12-Wpks-492 prenatal {253}  
  12-Wpks-493 postnatal {254}  
  12-Wpks-494 to 12-Wpks-511
postnatal {255-256} overall 18 cases  
  12-Wpks-512 prenatal {257}  
  12-Wpks-513 prenatal {258}  
  12-Wpks-514 to Wpks-523 postnatal {259; 260}  
  12-Wpks-524 postnatal {261} 1 case  
  12-Wpks-525 prenatal {0} provided by Dr. Eiben, Essen, Germany  
  12-Wpks-526 postnatal {262} 1 case  
  12-Wpks-527 postnatal {263} 1 case  
  12-Wpks-528 to 12-Wpks-548 postnatal {264} 21 cases  
  12-Wpks-549 postnatal {265} 1 case  
  12-Wpks-550 to 12-Wpks-555 postnatal {266} 5 cases  
  12-Wpks-556 postnatal {267} 1 case  
  12-Wpks-557 prenatal {268} 1 case  
  12-Wpks-558 to 12-Wpks-567 postnatal {269} 10 cases  
  12-Wpks-568 to 12-Wpks-587 postnatal {270} 20 cases  
  12-Wpks-588 postnatal {271} 1 case  
  12-Wpks-589 prenatal {273} 1 case  
  12-Wpks-590 to 591 prenatal {274} 2 cases  
  12-Wpks-592 to 594 postnatal {275} 3 cases  
  12-Wpks-595 to 599 prenatal {276} 5 cases  
  12-Wpks-600 prenatal {277} 1 case  
         

 


References

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  
  12-W-
pter/
1-1
female/
prenatal
AF de novo 47,XX,+mar[100%] inv dup(12)(pterp13.32:
:p11.22
p11.22q11:
:q11
p11.22::p13.32pter)*
array CGH see below {142}  
Child seen 3w after birth. With partial small bowel malrotation, hydrocephalus, macrocephaly infantile spasms, cortical visuals impairment, nasal dermoid on forehead, bifid uvula. At 3 y noted to have hypertelorism, downslanting palpebral fissure, short webbed neck, polythelia, 5th digit clinodactyly, hypotonia, inability to sit up without support. OFC in 25th centile. Profound developmentally delayed.
  12-W-
pter/
2-1
male/
postnatal?
PBL? n.a. 47,XY,+mar[46%]/
46,XY[54%]
mar(12)(:pterq11:) array-CGH abnormal {194} case 23919  
  12-W-
pter/
3-1
male/
postnatal?
PBL? n.a. 47,XY,+mar[63%]/
46,XY[37%]
mar(12)(:p13.33::p13.31p13.2:
:p11.23::p11.22
p11.21:
:?
12cen::p11.21p11.22:
:p11.23::p13.2
::p13.31::p13.33:)
array-CGH abnormal {194} case 31439  
  12-W-
p13/
1-1 °
male/
1w
PBL de novo 47,XY,+r[13]/
46,XY[7]
r(12)(::p13q11::)* SKY, cep 12; TEL-probe see below {114}  
born at term, weight: 3.1 kg, APGAR 6 at 1 and 5 min. immediate respiratory distress, cyanosis, and hypoxemia. Congenital heart malformation was suspected Chest roentgenogram revealed dextrocardia, mild cardiomegalie, increased pulmonary venous marking, and left aortic arch (the major axis of the heart oriented from left shoulder to right hip, with the morphologic left atrium located to the left of the morphologic right atrium), obstructed infradiaphragmatic TAPVR to the portal vein/inferior vena cava, large secundum atrial septal defect, and patent ductus arteriousus. All the pulmonary veins coalesced behind the right atrium into a common pulmonary venous confluence, which drained to the portal system. Splenic tissue in the left upper quadrant suggesting abdominal situs solitus. After surgery, secondary supraventricular tachycardia At 8 month weight: 15th, length: 50th centile, head circumference 15th centile; no developmental delay at this time.
  12-W-
p13/
1-2 °
female/
6m
PBL de novo 47,XX,+r[50%]/
46,XX[50%]
r(12)(::p13q11::) wcps for all chromosomes, cep 12; different FISH-probes as specified in {127} see below {127}  
born by cesarean section because placenta praevia, birth weight 3205g (50th centile), OFC 42.5cm (50th centile), no abnormality at birth noted; from birth on motor development delay retarded plus nystagmus; at 6m additionally noted hypotonia (esp. of trunk), decreases vision, nystagmus, alternating strabismus convergence; at 13m height 73cm (P10-P50), weight 9kg (P10-P50) OFC 45.2cm (P10-P50), plagiocephaly, protruding and low-set left ear, slight hypotonia; walking at 2y7m, speech severely delayed (at 3y only a few words); visual activity of 0.25 because of cerebral visual impairment; at 6y obesity (height 117 (P25), weight 29.4kg (3kg > P98), severe flat feet, speaking only single words and 2-word sentences.
  12-W-
p13.1/
1-1 °
female/
6m
PBL de novo 47,XX,+r[50%]/
46,XX[50%]
r(12)(::p13.1q1?::)* All wcp probes, cep12, 12p centromere near probes as specified in {13} see below {13}  
normal at birth; sSMC missed in prenatal diagnosis, which was done due to advanced  maternal age; at 6m motor retardation, poor visual contact, hypotonia, plagiocephaly, decreased vision, horizontal nystagmus
12-W-
p12.3/
1-1
male/
17y
PBL de novo 47,XY,+mar[22]/
46,XY[28]
r(12)(::p12.3p11.2::) midi and reverse FISH see below {0} provided by Lilia Kraoua, Tunis, Tunesia
at birth w: 3600g, lenght 51cm, OFC 37cm; inguinal hernia, cryptochidism, psychomotor delay, speech delay, seizures at 4y; mental tretardation; aggressive behaviour, insomnia, at 17y w 59kg, h: 170cm; PC 58cm, facial dysmorph, bilat. Camptodactyly and clinidactyly of 5th finger,  nystagmus, myopia
  12-W-
p12.2/
1-1
female/
1w
PBL de novo 47,XX,+r[100%] min(12)(::p12.2q13.11::)*
25.53-46.40 Mb p
resent on sSMC
M-FISH, array-CGH see below {144}  
Pregnancy and delivery normal, at birth weight 3485 g, APGAR score 7-9-10. Dysmorphic bilateral optic disc coloboma, small chin, broad mouth, large tongue, angulated ears, pronounced nuchal skin folds and bilateral partial syndactyly of second and third toes, patent ductus arteriousus, mildly reduced myocardial contractility. Brief myoclonic spasms in lower extremities observed 1month after birth. Shortly after this, generalized tonic-clonic seizures. The electroencephalogram was normal and computed tomography showed no radiological abnormalities of the brain and skull. Swallowing was difficult and there was hypertonia of lips and cheeks. At 15m received a percutaneous endoscopic gastrostomy. Weight and head circumference are within normal limits, whereas height is more than 3 SD above normal. She still often falls to one side when sitting, she can stand only when held and helped, does not yet walk and has mild flexion contractures of her knee joints
  12-W-
p12.1/
1-1
male/
n.a.
PBL de novo 47,XY,+r[63%]/
46,XY[37%]
r(12)(::p12.1q12::) centromeric probes, cep 12; YACs in 12q12, 12p11-p12.1; SOX-gene specific YAC see below {8}   
Uneventful pregnancy; born at term by cesarean section due to uterine inertia. Weight: 3520g; length 51cm; OFC 33cm; At birth. anorectal malformation with urethral fistula; skeletal X-ray showed multiple dorsal and lumbar hemivertebrae, sacral agenesis, multiple fused ribs; medullar lipoma; thickened terminal filum, hydromelia; absence of left kidney; normal psychomotor development
  ***
12-W-
p11.1/
1-1 °
***
male/
15y
PBL
(EKF-
cellbank)
de novo 47,XY,+r[21]/
46,XY[11]
min(12)(:p11.1q12:)
FISH-data: RP11-490D11 at 40.2MB on sSMC
cenM;
subcenM
psychomotor retardation; craniofacial dysmorphism {1} case 18  
  ***
12-W-
p11.1/
1-2 °
***
male/
2.5y
PBL de novo (?) 47,XY,+mar[100%] min(12)(:p11.1q11~12:)
FISH-data: RP11-490D11 at 40.2MB on sSMC
cenM;
subcenM
see below {125} case12-4  
Birth weight was 3.1 kg, length 50 cm and head circumference 35 cm. He presented mild retrognathia, feeding problems with poor sucking; psychomotor development retarded with delayed visual maturation; able to walk without support at the age of 18 months; At 2.5y psycho diagnostic testing revealed severe developmental delay (developmental level of 12 months at the age of 30 months) with autistic behavioral features; at age of 5y 4m severely mentally retarded; weight 17 kg (25th percentile), height 102 cm (third percentile); HF 48.8 cm (third percentile); general physical development is adequate; mild facial dysmorphism with large mouth, full lips, relative midface hypoplasia, small and conical teeth; except for two extra nipples on the right side and one on the left side, no other congenital malformations are present. Routine biochemical and metabolic screening and brain MRI scan are normal.
  12-W-
p11.1/
2-1 °
female/
1y 2m
PBL de novo 47,XX,+r[6]/
46,XX[24]
in FISH sSMC only in 9/90 cells
r(12)(::p11.1q14::)[7]/
r(12)(::p11.1
q11::)[2]
FISH-data; break in q14 between 46.63 and 56.12 MB
wcp12; MCB; subcenM; PCL-FISH
 
see below {110}
{228} case 13
 
second child of non-identical twins, born in week 37 of gestation; failure to thrive, recurrent respiratory tract infections, developmental delay, atrial septum defect, dysmorphic features like prominent metopic suture, down slating palpebral fissures, low set ears, long slim digits; weight and length <0.4 centile; OFC~3rd centile;
  12-W-
p11.1/
3-1
female/
10y
PBL de novo 47,XX,+mar[60%]/
46,XX[40%]
min(12)(:p11.1q11:) cenM;
subcenM
complex retardation, cleft palate, heart defect, pulmonalarterial stenosis, congenital microcephaly {0} provided by Dr. Demuth, Dresden, Germany  
  12-W-
p11.1/
3-2
female/
9y
PBL n.a. 47,XX,+mar[30%]/
46,XX[70%]
min(12)(:p11.1q11:) cenM;
subcenM
dwarphism, B-cell-leukemia at age of 6 years {0} provided by Dr. Gödde, Recklinghausen, Germany  
                     

 

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  
  12-W-
IMB-
p13
1-1 to
1-10
10 case with partial trisomy 12p are summarized in Ref {140} {140}  
  12-W-
IMB-
p13.2/
1-1
female/
19m
PBL de novo 46,XX,dup(12)(p11.2p13.2),trp(12)(p13.2 pter)[5%]/46,XX[15%] aCGH see below {241}  
  at 19m broad, high forehead, bitemporal balding, small posteriorly rotated ears, global developmental delays, and mild hypotonia; able to sit but not pull to a stand.  
  12-W-
IMB-
p12.3/
1-1
n.a./
postnatal
PBL paternal, unbalanced 46,XY,inv(12)(pterp11.22::q14.1p12.3::q14.1qter)
i.e. partial trisomy of 12p12.3-p11.2
BAC-FISH, array-CGH father and son with mental retardation and mild facial features {148}  
                   


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  
  12-
CW-1
male

2y

PBL de novo 47,XY,+mar[20%]/
46,XY[80%]
r(12) FISH with all available centromeric probes delayed development, vesico-ureteric reflux {6} case 5  
  12-
CW-2
female

7y

PBL de novo 47,XX,+mar[58%]/
46,XX[42%]
r(12)[52%]/
r(12;12)[6%]
telomeric probes; all centromeric probes in an array non-dysmorphic but moderate developmental delay {7} case 1  
                     

 

 


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  
  12-
U-1
female/
prenatal
AF de novo 47,XX,+mar[30%]/
46,XX[70%]
r(12) FISH with all available centromeric probes n.a., as pregnancy terminated and no autopsy performed {6} case 4  
  12-
U-2
male/
prenatal
AF
fetal blood
de novo 47,XY,+del(12)(q11)[40%]/
46,XY[60%]
n.a. n.a. n.a. {14} case VIIc-1  
  12-
U-3
see mult 2-13
{9;10} case 21a and 21b  
  12-
U-4
see McCl-12-Up13.1/1-1
{15}  
  12-
U-5
male/
prenatal
CH; AF de novo 47,XY,+mar[34]/
46,XY[16]
no mar in AF detected (number of analyzed cells?)
mar(12) .ish(wcp12+) all centromeric probes; wcp12 see below {117} case 10  
  CVS due to advanced maternal age; child born at term; weight: 2.877 kg. No anomalies were noted. The patient was lost to follow-up.  
  12-
U-6
n.a./
postnatal
PBL maternal
t(4;12)(p16;q11)
47,+mar[100%] der(12)t(4;12)(p16;q11) wcp 12, WHS-probe see below {131} case 1; {240}
 
 
craniofacial abnormalities (convex forehead, micrognathia, abnormal left ear), severe hypotonia, growth delay
  12-
U-7
male/
13 months
PBL de novo 47,XY,+mar[>30%]/
46,XY
dic(8;12)(8pterq11.1::12q11.112pter) n.a. see below {135}  
psychomotoric delay, dysmorphic features like macrocephaly, agenesis of corpus callosum, high and prominent forehead, hypertelorism, dysplastic ears, cleft palate, uvula bifida, zygodactyly of 2. and 3. toes and hearing impairment
  12-
U-8
female/
prenatal
AF de novo 47,XX,+mar[12]/
46,XX[3]
r(12) (:p11q12:)
RP11-242B24  and RP11-791O13 (38.11 MB) present on sSMC
array CGH, cep 12 AF due to advanced maternal age; no info available {143} case 1
{186} case 1
 
  12-
U-9
n.a./
prenatal
AF de novo 47,+mar[?%] min(12) n.a. n.a. {190} 1 case  
  12-
U-10
female/
prenatal
AF n.a. 47,XX,+mar[?%]/
46,XX[?%]
min(12) SKY AF due to advanced maternal age; no info available {221} case F0646031  

 
12-
U-11
female/
2y
PBL n.a. 48,XXX,+mar[6]/
46,XX[35]
min(12)(:p11.12q11:) midi; subcenM behavior problems and learning difficulties {0} provided by Dr. Guitart; Spain  
  12-
U-12
male/
prenatal
AF n.a. 47,XY,+mar[8]/
46,XY[16]
min(12)(:p11.1q11:) cenM; subcenM AF due to advanced maternal age; no info available {0} provided by Dr. Alves; Portugal  
  12-
U-13
female/
prenatal
AF n.a. 47,XX,+mar[19]/
46,XX[2]
mar(12) (:p11.22q12:)
aCGH: 29.20-38.71 MB
aCGH n.a.; TOP {235} case 14  
  12-
U-13
male/
postnatal
PBL n.a. 47,XY,+mar[50%]/
46,XY[50%]
der(12)(:q12p11.1::p11.1q12:) midi n.a. {0} provided by Dr. Weimer, Kiel, Germany
 
  12-
U-14
female/
postnatal
PBL pat bal. translocation 47,XX,+mar[100%] der(12;18)(p10;p10) M-FISH cleft palate, DD {271} case 2  
                     

 


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  
  12-N-
mar/1
n.a/
n.a.
PBL? de novo 47,+mar[?] mar(12) SKY see below {16} case 5  
global developmental delay; coarse facies, plus other dysmorphic features as seen on PKS; bifrontal sparseness of hair, abnormal placed prominent ears, mild hypertelorism, upslanting palpebral fissures, epicanthic folds, flattened nasal bridge, long philtrum, high arched palate
12-N-
pt13.33/
1-1

female/
~4y

PBL de novo 47,XX,+mar[70%]/
46,XX[30%]

der(12)(:p13.33p13.31:
:p13.31
p13.33:)

aCGH
cenM
see below
{278}  
skin showed linear, patchy or vortex-like pigmentary disturbances only partially arranged along atypical lines of Blaschko without any apparent midline separation  
  12-N-
pt13/
1-1
female/
3y
PBL de novo 47,XX,+mar[100%] ATYPICAL ACENTRIC PKS MARKER

inv dup(12)(pterp13::p13pter)

midi, M-FISH; cenM-FISH; array-CGH see below {119; 123; 146} {181} case 3  
Pregnancy and term delivery were normal. Birth weight 3.850 g (90th centile), length 53 cm (90th centile), head circumference 34 cm. No perinatal problems were noted; referred to a children’s hospital because of psychomotor developmental retardation; began sitting with assistance at 8 m and walking at 1 y 9 m; motor activity decreased; she presented with mental and speech delay; at 2 y 2 m weight 16.2 kg (97th centile), length 89 cm (75th centile), OFC 47.5 cm (10th - 25th centile); there was paratrophia (unusual for the age fat accumulation on buttocks and hips) and muscular hypotonia. Craniofacial dysmorphism included hypotrichosis (sparse scalp hair), a high forehead with high frontal hairline, mildly dysmorphic longish ears with hypoplastic antihelices and lobes, a round face, flat supraorbital regions, mild hypertelorism (3.2 cm), horizontal position of eye axes, flaring of lateral part of eyebrows, long straight eyelashes, a large nose with bulbous tip, full lips, short upper lip with short frenulum, high-arched palate, unusual configuration of both eyeteeth; broad neck, chest deformation (marked prominent of parasternal regions) and pilonidal dimple. Hands and feet were large with mild swelling of the dorsa as well as flat arches of the feet. At the age of 10 years: weight 46.5 kg (>97th centile), length 158 cm (>97th centile), OFC 52 cm (50th centile), profound mental delay, lack speech and self-help skills, behavioral abnormalities (irritability, aggressiveness) and abnormal gait, still muscular hypotonia and an unusually slow hair growth with sparsity of scalp hair bitemporal. At 12 10/12 y normal pubertal development with regular menarche, chronic rhinitis and caries. Hematological studies revealed a persistent leucopenia (first appeared at the age of 11.5 y).
  12-N-
pt12.3/
1-1
female/
1y
skin
fibroblasts
de novo 47,XX,+mar[13]/
46,XX[13]
ATYPICAL ACENTRIC PKS MARKER

inv dup(12)(pterp12.3: :p12.3pter)

MCB see below {3; 107; 118; 146}  
third child of healthy non-consanguineous parents, uneventful pregnancy, delivery spontaneous at term (birth weight 3.300g (50th centile), length 49cm (25th centile), head circumference (OFC) 33cm (10th centile), APGAR scores 10/10/10). At age of 1 month : apparent dysmorphic signs, heart murmur, hypotonia. Weight, length and OFC between the 3rd and 7th centile. Anomalies: bitemporal sparsity of hair, narrow prominent forehead, small ears, ptosis, hypertelorism, broad flat nasal bridge, small nose, long philtrum, thin upper lip, drooping lower lip and high arched palate. She had broad hands with terminal hypoplasia of fingers., apparently narrow pulmonary artery, slight supraventricular stenosis; small posterior-apical situated atrial septal defect. Diagnosis of PKS (Fig. 1). Seizures have been present since the age of 3 years.
nbsp] 12-N-
pt12.3/
1-2
male/
prenatal
AF n.a. 47,XY,+mar[16]/
46,XY[18]
ATYPICAL ACENTRIC PKS MARKER

inv dup(12)(pterp12.3: :p12.3pter)

FISH, MLPA sonographic abnormalities; left hydroureter, left hydronefrosis {196} case 6  
  12-N-
pt11.22/
1-1
male/
1y
PBL/ skin
fibroblasts/ buccal mucosa
de novo in blood: 46,XY

in fibro: 47,XY,+mar[18]/
46,XY[32]

ATYPICAL ACENTRIC PKS MARKER

inv dup(12)(pterp11.22: :p11.22pter)
buccal mucosa nuclei:
sSMC in 53%

HR-CGH, BACs see below {141}  
Normal pregnancy and delivery; birth weight 4940 g (>97th centile), length 53 cm (90th centile), OFC 'normal'. At 6m  psychomotor delay. At 2.5 y weight 13 kg (50th centile), length 87 cm (50th centile), head circumference 46cm (<3rd centile). Dysmorphic features incl. patchy front temporal alopecia, hypertelorism, long philtrum, low set posteriorly rotated ears, anteverted nostrils, epicanthal folds, bilateral simian crease, hypo pigmented skin whorls on trunk and limbs. Plus horizontal nystagmus, bilateral sensorineurak hearing loss, generalized muscular hypotonia, severe psychomotor retardation, speech absent. PKS like.
                     

 

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  
  12-N-
IMB-
pter/
1-1 to
?-1
cases reviewed in with (partial) trisomy of 12pter in {147-148} {158}
see also {182}
{147-148}
{149} 1 case {158}
{170}
 
  12-N-
IMB-
qter/
1-1 to
?-1
see {183} {183}