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

- sSMC -

CHROMOSOME 5

References

 

             
  Cases without
clinical findings
24 Cases with
clinical findings
30 symptoms  
  similar imbalances - no clinical findings similar imbalances with clinical findings  
    Cases with
isochromosome 5p
27    
  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 5
mat
UPD 5
pat
UPD 5
unclear
 
           

 


the probably non-dosage sensitive pericentric region of chromosome 5


SCHEMATIC CYTOGENETIC DEPICTION

tl_files/tiny_templates/Bilder TL/sSMC/sSMC-5.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 30.64 --- 37.21 uncritical region [45.80 centromere 50.50] uncritical region 55.27 --- 61.21 critical region

Below adapted for UCSC hg19, 2009

critical region 30.64 --- 37.17 uncritical region [46.10 centromere 50.70] uncritical region 55.22 --- 61.14 critical region

 


Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

5p - proximal 5q - proximal
symptoms
developmental delay 40 % (100 %)
dysmorphic face 90 %
(100 %)
growth retardation 20 % (50 %)
finger or toe/foot malformations 40 % 0 %
heart defect 40 % (50 %)
hernia 30 % 0 %
hypotonia 40 % (50 %)
hyperpigmentation 10 % 0 %
mental retardation 40 % 0 %
macrocephaly 30 % 0 %
seizures 10 % 0 %
vision impaired 20 % 0 %
number of cases (marked with “°” below) 10 2
 

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  
  05-O-
pter/
1-1
male/
28y
PBL n.a. 47,XY,+mar[3%]/
46,XY[97%]
min(5)(pterq11.1:) M-FISH, pcp 5p normal male, studied due to repeated abortions in partner {55}
{57} case 5-1
 
  05-O-
pter/
2-1
moved to 05-W-iso/1-19 {42; 55}  
  05-O-
pter/
2-2
moved to 05-W-iso/1-23 {47} case 2; {55}
 
  ***
05-O-
p13.2/
1-1

***
female/
adult
PBL de novo 47,XX,+mar[100%] min(5)(:p13.2q11.1:)
37.55-46.14 MB
subcenM;
array-CGH
normal woman studied due to three neonatal deaths due to respiratory failure {36} case P-3, {56}
 
  ***
05-O-
p13.2/
1-2
***
female/
prenatal
AF de novo 47,XX,+mar[25]/
46,XX[25]
min(5)(:p13.2q11.2:)[5]/
min(5)(:p13.2
q11.2:
:q11.2
p13.2:)[4]/
r(5)(::p13.2
q11.2::)[8]/
r(5)(::p13.2
q11.2:
:p13.2
q11.2::)[2]
37.21-55.27 MB
cenM;
subcenM;
array-CGH;
UPD-test
advanced maternal age, normal child born; normal at 2 years {53} case Srm-1  
  05-O-
p13.1/
1-1
male/
30y
PBL n.a. 47,XY,+mar[50%]/
46,XY[50%]
min(5)(:p13.1q11.1:)[5]/
r(5)(::p13.1
q11.1::)[3]/
r(5;5)(::p13.1
q11.1:
:p13.1
q11.1::)[2]
FISH-data:
RP11-19F12 (41.24MB) on sSMC
cenM;
subcenM
repeated abortions in partner, otherwise normal male {57} case 5-2
 
  05-O-
p13.1/
1-2
female/
prenatal
AF n.a. 47,XX,+mar[7]/
46,XX[43]
min(5)(:p13.1q11.1:)
mat isoUPD 5 - mar pat derived
cenM;
subcenM
no sonographic signs; advanced maternal age, child born; no abnormalities reported; slight hip dislocation {0} provided by Dr. Schulze, Hannover, Germany
 
  05-O-
p13.1/
2-1
female/
prenatal
AF n.a. 47,XX,+mar[40]/
46,XX[60]
min(5)(:p13.1q11.2:) cenM;
subcenM
advanced maternal age, normal child born; normal at 6 months {0} provided by Dr. Henn, Homburg, Germany
 
  05-O-
p12/
1-1
female/
38y
PBL
(EKF-
cellbank)
n.a. 47,XX,+mar[100%] min(5)(:p12q11.1:)
FISH-data:
RP11-19F12 (41.24MB) on sSMC
cenM;
subcenM
sSMC detected in preparation to ICSI; otherwise normal woman {26} case 9
{57} case 5-3
 
  05-O-
p11.2/
1-1
n.a./
prenatal
AF de novo 48,+mar1,+mar2[88%]/
47,+mar1[12%]
mar(5)(:p11.2q11.1:)/
mar(5)(:p11.1
q11.2:)
n.a., subcenM with 3 BACs, array-CGH see below {20} case 10  
At 15 months of age, patient appears normal with no dysmorphic features or developmental delay (marker detected on amniocentesis for increased Down syndrome risk on serum screen).
  05-
O-p11/
1-1
female/
prenatal
AF de novo 47,XX,+mar[38]/
46,XX[15]
min(5)(:p11q11.2:) cenM;
MCB
Amniocentesis due to advanced maternal age; child born without any signs or symptoms {1} case 11  
  05-O-
p11/
2-1
female/
prenatal
AF n.a. 47,XX,+mar[50%]
46,XX[50%]
min(5)(:p11q11.1:
:q11.1
p11:) or
min(5)(:q11.1
p11:
:p11
q11.1:) or
min(5)(:p11
q11.1:
:p11
q11.1:)
cenM;
subcenM
see below {0} provided by Dr. Duba, Linz, Austria  
Amniocentesis due to advanced maternal age and 1 previous abortion; in week 23 no ultrasound abnormalities; in week 30: head circumference 25.5 cm, femur length 53mm, weight ~1136g; at birth normal: (41. week) APGAR 9/10/10; weight 2840g, length 49cm, head circumference 33cm
  05-O-
p11/
3-1
female/
25y
PBL de novo 47,XX,+mar[100%] min(5)(:p11q11.1:) cenM;
subcenM
normal female {0} provided by Dr. Cremer, Düsseldorf, Germany  
  05-O-
p11/
3-2
male/
33y
PBL de novo 47,XY,+mar[9]/
46,XY[22]
min(5)(:p11q11.1:) cenM;
subcenM
normal male, fertility problems {57} case 5-4
 
  05-O-
p11/
3-3
male/
40y
PBL n.a. 47,XY,+mar[77]/
46,XY[18]
min(5)(:p11q11.1:) cenM;
subcenM
normal male, fertility problems {57} case 5-5
 
  05-O-
p11/
3-4
male/
adult
PBL n.a. 47,XY,+mar[100%] min(5)(:p11q11.1:) cenM;
subcenM
normal male, same sSMC in his unborn child {0} provided by Dr. Alves, Porto, Portugal  
  05-O-
p11/
3-5
female/
prenatal
AF de novo 47,XX,+mar[100%] min(5)(:p11q11.1:) cenM;
subcenM
advanced maternal age, normal sonography, normal child born; normal at 3 y of age
{0}  
  05-O-
p11/
3-6
male/
prenatal
AF de novo 47,XY,+mar[70%]/
46,XY[30%]
min(5)(:p11q11.1:) cenM;
subcenM
advanced maternal age, normal child at 3m postnatal
{0} provided by Dr. Petersen, Greece
 
  05-O-
p11/
4-1
female/
prenatal
AF n.a. 47,XX,+mar[100%] min(5)(:p11q11.1~11.2:)
FISH-data: RP11-160F8 (53.52MB) on sSMC
cenM;
subcenM;
UPD-test
advanced maternal age - US normal, normal child born {0} provided by Dr. Borochowitz, Haifa, Israel  
  05-O-
p11/
5-1
moved to McCl-5-W-p11/1-1 {35}  
  05-O-
p11/
6-1
male/
45y
PBL n.a. 47,XY,+mar[80%]/
46,XY[20%]
min(5)(:p11q11.1:)[34]/
min(5)(:p11
q11.1:
:p11
q11.1:)[9]
cenM;
subcenM
normal male, fertility problems {57} case 5-6
 
  05-O-
p10/
1-1
male/
prenatal
CH n.a. 47,XY,+mar[?%]/
46,XY[?%]
i(5)(:q11.1~11.2p10:
:p10
q11.1~11.2:)
FISH-data: RP11-160F8 (53.52MB) on sSMC
wcp-studies, subcenM see below {0} provided by Dr. Mazaurik, Düsseldorf, Germany  
sSMC detected due to advanced maternal age; originally twin pregnancy; normal ultrasound; at birth normal child - birth by sectio; weight: 3210g, length 48cm, OFC 35cm; APGAR 9/10/10,
                     

 

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  
  05-O-
IMB-
q11.1/
1-1
female/
40y
PBL n.a. der(5)(pterq11.2:
:q11.1qter)
subcenM normal female, dup found in unborn child
{0} provided by Dr. Shoukier, Munich, Germany
 
                     

 

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  
  05-
CO-1
male/
prenatal
AF, CH, chord blood de novo 47,XY,+mar[60]/
46,XY[40]
in CH: 37.8% with sSMC
in blood: 33.7% with sSMC
mar(5)(:p?15~13q1?1:)* cep probes, wcp5
RX-FISH
Amniocentesis due to advanced maternal age; child born without any signs or symptoms, normal at 2y {18} case 1  
  05-
CO-2
n.a./
prenatal
AF paternal 47,+mar[50%]
46[50%]
mar(5) cenM Amniocentesis due to advanced maternal age; no info on child; father normal {0}  
                     

 


References


Cases with iso-chromosome 5p (W-iso)


 
  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  
  05-W-
iso/
1-1 to 1-3
inv dup(5)(pter→q10::q10→pter) 3 cases {30} 3 case summarized (Lorda-Sánchez et al. 1997, Sijmons et al. 1993; Stanley et al., 1993)  
  05-W-
iso/
1-4
female/
prenatal
AF de novo 47,XX,+mar[10]/
46,XX[20]
inv dup(5)(pterq10:
:q10
pter)
M-FISH; pcp5 different ultrasound abnormalities {51} case 2  
  05-W-
iso/
1-5 to
1-6
female/
prenatal
AF de novo 47,XX,+mar[5]/
46,XX[10]
or
47,XX,+mar[10]/
46,XX[5]
inv dup(5)(pterq10:
:q10
pter)
wcp 5? different ultrasound abnormalities {19}cases 54-55  
  05-W-
iso/
1-7
male/
prenatal
CH/AF de novo CH: 47,XY,+mar[4]/
46,XY[26]
AF: 47,XY,+mar[24]
inv dup(5)(pterq10:
:q10
pter)
D5S23, D5S721 see below {37} twin A  
different ultrasound abnormalities in one twin; spontaneous abortion of both twins; autopsy showed among others tiny palpebral fissure, cystic hygroma, cleft palate, abnormal positioning of great toes, bilateral clubbed feet,, obstructive renal changes, hypoplastic bladder, hypospadias, unspecified cardiac defect, omphalocele, imperforate anus, oligohydramnios
  05-W-
iso/
1-8
male/
prenatal
AF, fetal tissues de novo AF: 47,XY,+mar[12]/
46,XY[28]
skin: mar in 4/40 - absent in kidney and pancreas
inv dup(5)(pterq10:
:q10
pter)
subtel 5pter
pcp 5p
no ultrasound abnormalities, advanced maternal age; in autopsy: long philtrum, up-slanting palpebral fissures and a broad nasal bridge {38}  
  05-W-
iso/
1-9
female/
prenatal
CH, fetal tissues de novo CH short term: 47,XX,+mar[7]/
46,XX[5]
CH long term: 47,XX,+mar[20]

see below
inv dup(5)(pterq10:
:q10
pter)
subtel 5pter
pcp 5p
increased nuchal translucency at 11 weeks’ gestation, suggesting cystic hygroma - also later congenital heart defect (pulmonary atresia with intact ventricular septum), TOP {39}  
skin mar in 3/18 , kidney in 1/10, lungs in 4/14, umbilical cord tissue in 1/13
  05-W-
iso/
1-10
female/
prenatal
AF/ CH de novo 47,XX,+mar[10]/
46,XX[5]
CH: mar in 6/21
inv dup(5)(pterq10:
:q10
pter)
wcp 5; D5S23, cep 1/5/19 different ultrasound abnormalities, cystic hygroma, choroid plexzs cysts; intrauterine fetal death at 28 weeks {40}  
  05-W-
iso/
1-11
n.a./
prenatal
CH/ skin de novo 47,+mar inv dup(5)(pterq10:
:q10
pter)
n.a. different or no ultrasound abnormalities, TOP {41} case 2  
  05-W-
iso/
1-12
female/
prenatal
CH/  fetal tissues de novo 47,XX,+mar[11]/
46,XX[6]
kidney in 3/20; gut in 6/20; skin in 5/20
inv dup(5)(pterq10:
:q10
pter)
n.a. increased nuchal translucency, TOP {41} additional case  
  05-W-
iso/
1-13 to 1-18
3x female, 2x male/prenatal and/or postnatal CH/ AF/ PBL de novo cases 1, 3, 4, 5: mar only in CH
case 6: mar only in CH and 2% in AF
case 7: mar only in 2% in AF
in none of the cases in PBL
inv dup(5)(pterq10:
:q10
pter)
n.a. normal at birth or as newborn or 4m to 4y {41} cases 1, 3, 4, 5, 6, 7  
  05-W-
iso/
1-19
male/
35y
PBL de novo 47,XY,+mar[8]/
46,XY[42]
mar not present in skin fibroblasts or urothelial cells
inv dup(5)(pterq10:
:q10
pter)
subtel 5pter fertility problems {42; 55}  
  05-W-
iso/
1-20
female/
5y
PBL/ skin de novo 47,XX,+mar[11]/
46,XX[6]
'overall sSMC in 10% of skin fibroblasts - only hyperpig. area'
in blood no sSMC
inv dup(5)(pterq10:
:q10
pter)
wcp 5, locus spec. probe see below {43}  
early development was uneventful and apparently normal, although she had been seen by a physiotherapist at the daycare centre for motor delay. At 5y psychomotor and intelligence testing showed values at the lower normal border broad facies, broad nasal tip and clinodactyly of the little finger, focal hyperpigmentation of skin
  05-W-
iso/
1-21
n.a./
prenatal
CH/ skin de novo CH: 47,+mar[7-20%]/
46[80-93%]
skin: in 13%
inv dup(5)(pterq10:
:q10
pter)
probes n.a. advanced maternal age; TOP; fetus had some dysmorphic features hypertelorism, a wide nasal bridge, microgantia, small earlobes, a hypoplastic right upper lung lobe and a bicornate uterus. {45}  
  05-W-
iso/
1-22
n.a./
prenatal
CH/AF/ PBL/ urine de novo CH: 46[15]
AF: 47,+mar[4]/
46[37]
postnatal 5% in PBL and urine
inv dup(5)(pterq10:
:q10
pter)
probes n.a. fetus with lat facial profile, at birth facial abnormalities; at 5y mental retardation, hydrocephaly, club foot {47} case 1  
  05-W-
iso/
1-23
female/
prenatal
AF/ PBL/ skin with hyperpigmentation/ buccal mucosa de novo AF: 47,XX,+mar[1]/
46,XX[14]
see below
inv dup(5)(pterq10:
:q10
pter)
probes n.a. amniocentesis due to isolated polyhydramnion; facial dysmorphism after birth; at 5y normal {47} case 2; {55}  
no sSMC in postnatal PBL; in skin with hyp.: 85% with mar; in normal skin: 13% with sSMC; in buccal muc: 70% with sSMC
  05-W-
iso/
1-24
male/
prenatal
AF/ PBL/ skin de novo AF and PBL at 2y: 46,XY
skin fibroblasts: 47,XY,+mar[7]/
46,XY[44]
inv dup(5)(pterq10:
:q10
pter)
wcp5, aCGH i5p syndrome {48}  
  05-W-
iso/
1-25
male/
prenatal
CVS/PBL/ skin de novo CVS: 47,XY,+mar[1]/46,XY[216]
PBL: 47,XY,+mar[3]/46,XY[28]
skin fibroblasts: 47,XY,+mar[12]/
46,XY[2]
inv dup(5)(pterq10:
:q10
pter)
n.a. i5p syndrome {49}  
  05-W-
iso/
1-26
female/
5y
PBL/ skin de novo PBL: 46,XX
skin fibroblasts: 47,XX,+mar[?%]/
46,XX[?%]
inv dup(5)(pterq10:
:q10
pter)
n.a. i5p syndrome {50}  
  05-W-
iso/
1-27

male/
prenatal

CVS n.a. 47,XY,+mar[15]/46,XY[7] inv dup(5)(pterq10:
:q10
pter)
subcenM i5p syndrome {0} provided by E. Manolakos, Athens, Greece  
                     

 


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  
  05-W-
p15.33/
1-1
n.a./
prenatal
AF de novo 47,+mar[100%] min(5)(pterq11.1:) M-FISH; pcp5 see below {0} provided by Dr. Yardin, France  
Amniocentesis due to advanced maternal age; ultrasound signs presented by the fetus are compatible with the trisomy 5p and included: dolichocephaly with prominent forehead and retrognathia,  ventriculomegaly, club feet, femur length under 10the centile, intra-abdominal massvisible and attributed to renal cysts. TOP, but no autopsy.
05-W-
p15.33/
1-2
female/
prenatal
CVS/ PBL de novo

CVS: 92,XXXX/ 46,XX
PBL: 47,XX,+mar[100%]

min(5)(pterq11.1:) wcp5 several dysmorphic features and a severe failure to thrive {61}
  05-W-
p15.33/
1-2
male/
prenatal
AF de novo 47,XY,+mar mar(5?p) wcp 5? ultrasound abnormalities {19} case 53
{43}
 
  05-W-
p15.33/
1-3
female/
prenatal
AF de novo 47,XX,+mar min(5)(pterq10:) MCB 5 ultrasound abnormalities, TOP {27} case 1  
  05-W-
p15.33/
1-4
n.a./
prenatal
AF de novo 47,+mar min(5)(pterq10:) n.a. ultrasound abnormalities, TOP {34} 1 case  
  05-W-
p15.3/
1-1
female/
postnatal
PBL de novo 47,XX,+mar[11]/
46,XX[11]
min(5)(pterq11.2:)
32.73-55.80 MB
aCGH DD, MR {52} case 5  
  05-W-
p14/
1-1
female/
27y
PBL n.a. 47,XX,+r[39]/
46,XX[29]
r(5)(::p14q11.2::)
16.58-56.31 MB
r(5)(::p15.1
q11.2::)
(sSMC is a derivative of a maternal chromosome 5)
midi; FISH;  array-CGH; UPD test see below {0}
{5} case 1
 
Born after uncomplicated pregnancy; speech with 4y; mental development delayed; at age of 27 dysmorphic face (small face, epicanthic folds, high arched palate, hypertelorism, left strabismus, upward slanting palpebral fissures, synophris, prominent nose with wide nasal bridge, micrognathia, low set, posteriorly rotated, dysplastic ears, low frontal and posterior hairline); bilateral talipes valgus and genu valgum, Baker's cysts
05-W-
p14.1/
1-1
female/
10y
PBL n.a. 47,XX,+r r(5)(::p14.1q11.1::)
array-CGH 49.7-45.80 MB
array-CGH see below {44; 60}
born at term after uneventful pregnancy; at 10 years facial dysmorphism, moderate mental retardation; pointed chin, flat nasal bridge, left-deviated nasal septum, hypertelorism, mid-facial hypoplasia, blepharophimosis, prognatism, pectus excavatum and inverted nipples, hypoplasic maxilla and ossis nasi, hypoplastic cervical vertebrae I-II. Psychological survey showed slight developmental delay. diagnosed as Binder syndrome.
  05-W-
p1?4/
1-1
female/
3m
PBL n.a. 46,XX,1qh+pat[70]/
47,XX,1qh+pat,+mar dn[30]
?r(5)(::p1?4->q11.1::)[3]/?min(5)(:p1?4->q11.1:)[1] cenM/ subcenM see below
{0} povided by Dr. J. Wagner, Osijek, Croatia  
  twins pregnancy eneded by  emergency cesarean section (asphyxia). At birth 2130g, 45 cm, APGAR 2/7. At 2 m dysmorphic, at 3m; hypertelorism, broad nasal root, microretrognatia, gothic palate, umbilical hernia, hypotonic.  
  05-W-
p13/
1-1
see McCl-05-W-p13/1-1 {6}  
  05-W-
p13.3/
1-1
°
female/
1w
PBL de novo 47,XX,+r[31]/
46,XX,[9]
r(5)(::p13.3q10::) all wcp; different YACs see below {8} case 1  
Birth weight 2050g (<3. centile), OFC 33.5cm (>50. centile); length 44cm (10. centile); APGAR 6/8/-; during pregnancy polyhydramnion and fetal distress; at birth hypotonia and talipes equinovarus; At 3.5m length still at 3. centile, macrocephaly, with OFC at 75. centile, narrow up slanting palpebral fissures, epicanthic folds, hypertelorism, flat nasal bridge, short nose, broad alveolar margins, simple eras, long hands and fingers, right transverse palmar crease, protuberant abdomen, narrow chest, developmental delay, at 9m seizures; dies at 3y, 3m due to respiratory failure
  05-W-
p13.3/
1-2
male/
1w
PBL de novo 47,XY,+r[25]/
46,XY[6]
r(5)(::p13.3q12.3::) all wcp; different YACs see below {8} case 2  
Polyhydramnion during pregnancy, Birth weight at 75. centile, OFC  >95. centile,  length at 5o. centile; APGAR 6/7/-; macrocephaly, large anterior fontanel, upslanting palpebral fissures, wide nasal bridge, abnormal ears, preauricular pits, bilateral palmar crease, cardiac murmur, anterior anus, bilateral talipes equinovarus, hypotonia, VSD, hydrocephalus, bilateral inaugurine hernia, facial eczema at 9m, dolichomacrocephaly, weight and length later below 3. centile
  ***
05-W-
p13.3/
1-3°
***
male/
5y
PBL maternal
(mother with 20% sSMC)
47,XY,+mar[50%]/
46,XY[50%]
min(5)(:p13.3q11.1:)
30.64-46.14MB
FISH-data: RP11-19F12 (41.24MB) on sSMC
array-CGH (Agilent 44000) see below {36} case P-2  
mental retardation, facial dysmorphism and aggressive behavior; brother with sSMC ion 90% of cells also with mental retardation; mother also with mental retardation
  05-W-
p13.3/
2-1
female/
~1m
PBL de novo 47,XX,+mar[~70%]/
46,XX[~30%]
min(5)(:p13.3~p13.2q11.2:) M-FISH, subcenM, MCB see below {16}  
Karyotyped initially because of ASD, VSD and odd facies; walked at 18 months of age; moderate learning difficulties but attends normal school; mother describes her as "slow" and "heavy" when she has tasks to perform; Weight was 55.6 kg (> 97th pc), length 148.2 cm (92nd pc), span 151.2 cm, OFC 57 cm (>97th pc) cm, and ears 6 cm (55th pc) at the age of 9 years and 8 months. Tanner was at state II; mild dolichocephaly, low set ears with preauricular pits, broad eyebrows, hypertelorism, down slanted palpebral fissures, heavy epicanthus, high nasal bridge, tongue with a vertical furrow, thick thorax with 85 cm circumference (> > 97th centile), imd 18.3 cm (90th pc), 2 supernumerary nipples, tapering fingers, palms 9.6 cm (85th pc), middle finger 7.5 cm (> 97th pc), thumb distally placed, foot length 24.2 cm (97th pc), and clino/camptodactyly of toes IV and V. She began to gain weight from ~ 7 years of age. Ophthalmological investigation and abdominal U/S were normal.
  05-W-
p13.2/
1-1
°
male/
1m
PBL
(EKF-
cellbank)
de novo 47,XY,+mar[7]/
46,XY[3]
r(5)(::p13.2q11.1::)[9]/
r(5;5)(::p13.2
q11.1:
:p13.2
q11.1::)[1]
M-FISH,
subcenM MCB
see below
{0}  
  minor dysmorphic signs (microgenia, thin upper lip, hypoplasia of the midface, upslanting palpebral fissures), inguinal hernia, hypotonia, no glaucoma; at 5y slight developmental delay; strabismus since 6 y; at 7y: ADHD; IQ75; obstusive behaviour; tendency to runaway; bulbous nose and "ears attached more backwards than normal"
 
  05-W-
p13.2/
2-1°
male/
prenatal
AF/ PBL
(EKF-
cellbank)
de novo 47,XY,+mar[AF 24; PBL 28]/
46,XY[AF 6; PBL 3]

min(5)(:p13.2q11.2:)
aCGH: break in p-arm at position 34,531,621-55,293,501
FISH-confirmed

wcp, subcenM, BAC in 5p13.2
aCGH
see below {51} case 3
{0}
 

advanced maternal age, normal sonography; polyhydramnios a week before the birth, after birth no major physical problems; problems with suckle; slightly unsual ears (a bit low set), shape of eyes, possible epicanthus and small eyes, slight squashed nose, also quite long fingers and toes. At 6 months developmental delay, still tube fed, not sitting yet, but smiled at 2 months and can roll over, touch his feet, and pull toys. Walking at 20 m. At 4 y diagnosis of mild autism and no speach, but knowing all letters and numbers and able to spell ~20 words on magnetic board.Dysmorhic signs became very mild at 4 y. Even though having mild autism he is smiley and affectionate person loving cuddles and being wizz in ipad.

  05-W-
p13.2/
2-2
female/
prenatal
AF n.a. 47,XX,+mar[100%] mar(5)(:p13.2q11.1:)
aCGH: 34.93-45.32
aCGH see below {54} case 6
 
advanced maternal age, TOP - no further information available
05-W-
p13.2/
2-3 °
female/
10m
PBL n.a. 47,XX,+mar[100%] min(5)(:p13.2q11.1:) cenM; subcenM
see below {0} provided by Dr. Midyan, Yerevan, Armenia
congenital heart disease (ventricular septal defect, secondary atrial septal defect, cardiac insufficiency) and convergent strabismus, horizontal nystagmus, micro-retrognathia
  05-W-
p13.1/
1-1
°
female/
prenatal
AF/PBL de novo 47,XX,+mar[100%] mar(5)(:p13.1q10:) midi see below {9}  
Amniocentesis due to triplet gestation and advanced maternal age; other two triplets with normal karyotypes; IUGR from week 27 on; polyhydramnion (>95. centile); birth weight at 15. centile, length at 10. centile, OFC at 25. centile; other two triplets had normal values; postnatal treatment for presumed sepsis, apnea, hyperbilirubinemia, hypoglycemia, anemia; At 1m length and weight <5. centile, OFC at 30. centile, large anterior fontanel, umbilical hernia, skin with visible venous patterning;  hypotonia, VSD; at 3 and 5m weight and length <3. centile; OFC at 90. centile; dolichocephalism, hypertelorism, epicanthal folds, upslanting palpebral fissures, short nose, arachnodactyly
05-W-
p13.1/
2-1
male/
1 month
PBL de novo 47,XY,+mar[1]/
46,XY[44]
mar(5)(:p13.1q11.2:) FISH DYS, axial hypotonia GGB03237M, 2318 provided by Teleton foundation, Italy
  05-W-
p12/
1-1
°
n.a./
prenatal
AF
PBL
fibroblasts
de novo 47,+mar[46%]/46[54%]
47,+mar[62%]/46[38%]
47,+mar[50%]/46[50%]
r(5)(::p12q10::) midi see below {2} case G  
Amniocentesis due to advanced maternal age. The parents elected to terminate the pregnancy in week 19. autopsy showed normal weight, length, and head circumference, but also an asymmetrical head & face, left ear smaller & set lower than the right ear; short & upturned nose, long, marked philtrum, small chin, neck short & broad, with a slight excess of nuchal skin. Except for a small VSD, no major malformations were found.
  ***
05-W-
p12
/

2-1°
***
female/
prenatal
AF
PBL
de novo 47,XX,+mar[11]/
46,XX[5]
min(5)(:p12~13.1q10:)[11]/
min(5)(:p12~13.1
q10:
:q10
p12~13.1:)[2]/
r(5)(:p12~13.1
q10:
:q10
p12~13.1:)[1]
aCGH: 30.28-45.87
midi; subcenM; array-CGH see below {13} case 5-6
{0}
 
Advanced maternal age; child born with facial dysmorphism in week 34 (macrocephalus, long face, epicanthus, deep set big ears, short mouth), microgeny, rectus diastasis, small umbilical hernia, bilateral club feet and sandal gaps; VSD; ASDII; birth weight: 2650g, length 47cm, OFC 36.5cm; speech: 'mom' and 'dad' at 2y, at 3y 10 words only. Crawling with 16m, sitting with 13m; no hearing problems diagnosed;  at age of  3y minor psychomotor developmental retardation, hypothyreosis; weight 15.5kg, length 92cm, OFC 53,6cm; adipositas, deep sitting, dysplastic ears, epicanthus, hypertelorism, hypotonia of facial muscles, sandal gaps; a age of 2.5 fever cramp - however, EEG normal at birth and at 3y.
  05-W-
p12/
3-1
°
male/
postnatal
PBL
cell line at ECACC DD0549
de novo 47,XY,+mar(19)[?%]/
47,XY,+mar[%?]/
46,XY[?%]
inv dup(5)(:p12q11.1:
:q11.1
p12:)[60%]
no other marker observed
cenM; subcenM; hypotonic, moderately retarded {15} case 5  
  05-W-
p11/
1-1
°
n.a./
1y
PBL de novo 47,+mar[25%]/
46[75%]
r(5)(::p11q12.1::) n.a.; subcenM with 3 BACs; array-CGH see below {20} case 9  
Intrauterine growth retardation (IUGR) and small for gestational age (SGA); at 55 days of age in the neonatal intensive care unit (NICU): apnea, poor feeder, elevated triglycerides, normal head ultrasound, mild dysmorphic features; at 1 year of age: developmental delay, mild dysmorphic features, atrial septal defect, hemangiomas.
  ***
05-W-
p11/
1-2
°
***
female/
4y
PBL de novo 47,XX,+mar[14]/
46,XX[6]
r(5)(::p11q12.1::)
aCGH: 46.15-61.33 MB
midi, subcenM
array-CGH;
UPD-test
see below {46}  
Normal delivery, weight 2750g, Childhood: Hypotonic, psychomotor delay, first sentence at 4y, learning difficulties; slight facial dysmorphism - thin upper lip, slight hypertelorism; slight protrusion of the chin Chorioretinitis. Adulthood: Son with normal karyotype
  05-W-
p11/
1-1
female/
postnatal
PBL n.a. 47,XY,+mar[100%] min(5)(:p11q11.1:) cenM; subcenM; abnormal phenotype {0} provided by Dr. A. Polityko, Minsk, Belarus  
                     

 

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  
  05-W-
IMB-
p13/
1-1
male/
2y
PBL maternal
(balanced inversion)
46,XY,dup(5)(p13p11) n.a. macro-dolichocephaly, mentally retarded, multiple minor anomalies {31}  
  05-W-
IMB-
p13.3/
1-1
n.a./
postnatal
PBL maternal
(balanced )
46,der(19)ins(19,5)(p11;p11p13.3) n.a. see below {22}  
similar to those described in patients with complete duplication of the short arm and in some patients with partial 5p duplications, affecting at least band 5p13
  05-W-
IMB-
p12/
1-1
male/
18y
PBL de novo 46,XY,dup(5)(p12q11) subcenM height and head circumference under the 3rd percentile, severe mental retardation {1} case II  
  05-W-
IMB-
q11.2/
1-1
male/
postnatal
PBL paternal (balanced) 46,XY,der(20)t(20;5)(q11.2;q11.2q13.1) n.a. feeding difficulties, gross motor delay, few minor abnormalities {25; 32; 33}  
                   


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  
  05-
CW-1
male/
8m?
PBL de novo 47,+r[24%]/
46[26%]
.ish r(5)(wcp5+;D5Z2+) different FISH probes: cep 1/5/19; wcp5 see below {4}  
Born at 39 weeks of gestation; weight 2,540 g (-1.7 SD), length 47.6 cm (-1.1 SD), and OFC 32.8 cm (-0.5 SD); congenital stridor due to laryngomalacia,  telecanthus, low nasal bridge, hypoplastic columella, preauricular tag, and high-arched palate. He sat alone at age 8 m and walked at 17 m. He twice had febrile convulsions. Computed tomography of the brain was normal as were fundi. At age 3 2/12y  height 97.4 cm (+0.8 SD), weight 15.7 kg (+0.9 sm, and OFC 50.5 cm (+0.5 SD). He spoke no meaningful words.
  05-
CW-2
n.a./
n.a.
n.a. n.a. 47,+mar[?%] mar(5) FISH with ? developmental abnormal {12} 1 case  
  05-
CW-3
male/
newborn
PBL de novo 47,XY,+mar[23]/
46,XY[1]
mar(5) M-FISH; cep 1/5/19 normal pregnancy and birth, failure to thrive, hoarse voice on crying, growth retarded, isolated cleft palate, {29} 1 case  
                     

 

 


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  
  05-
U-1
n.a./
n.a.
n.a. n.a. 47,+mar min(5) SKY n.a. {3} case 12  
  05-
U-2
see mult 2-19
   
  05-
U-3
n.a./
prenatal
AF de novo 47,+mar[18]/
46[7]
r(5) cep probes
wcp 5
Amniocentesis due to advanced maternal age, TOP - no follow up {14} case 18  
  05-
U-4
female/
31y
PBL n.a. 47,XX,+mar[?%] min(5)(:p12q11.1:) cenM, subcenM n.a. {0} provided by Dr. Ivan Iourov, Moscow, Russia  
  05-
U-5
female/
prenatal
AF
chord blood
de novo AF: 47,XX,+mar[20]/46,XX[20]
chord blood: 48,XX,+mar[2]/
47,XX,+mar[20]/46,XX[10]
min(5)(:p12q11.1~11.2:) cenM; subcenM no ultrasound abnormality in week 22; TOP;  autopsy findings at 8 lunar months: length 43cm, weight 1940g - no internal or external abnormalities {0} provided by Dr. Gordana Joksić, Belgrade, Yugoslavia  
  05-
U-6
male/
prenatal
AF n.a. AF: 47,XY,+mar[100%] min(5)(:p11q11.2:) cenM; subcenM;
UPD-test
borderline ventriculomegaly on both sides, no further information available {0} provided by Dr. Mehnert, Neu-Ulm, Germany  
  05-
U-8
female/
prenatal
AF n.a. 47,XX,inv(19)(p11~12q12),+mar[44]/46,XX,inv(19)(p11~12q12)[12] min(5)(:p11q11.1:) cenM; subcenM advanced maternal age, twin pregnancy after ICSI {0} provided by Dr. Cremer, Düsseldorf  
  05-
U-9
male/
prenatal
AF n.a. 47,XY,+mar[4]/46,XY[11] min(5)(:p11q11.1:) cenM; subcenM advanced maternal age, no sonographic signs
{0}
provided by Drs. Körte Jung, Düsseldorf
 
  05-
U-10
male/
prenatal
AF/ PBL de novo AF: 47,XY,+mar[40%]/46,XY[60%]
PBL: 47,XY,+mar[80%]/46,XY[20%]
mar(5) wcp 5;cep 1/5/19 heart defect, forman avle apertum, astmatic attacks, failure to thrive, inguinal and umbilcal hernia, polydactyly, short neck, dysmorphic signs, ventzriculomegaly, axial hypotonia
{58}  
  05-
U-11
male/
prenatal
AF n.a. 47,XY,+mar[100%] mar(5)(pterq11.2:
:p15.?2
pter)
cenM; subcenM

n.a.

{0} provided by Dr. Schulze, Hannover, 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  
  05-
N-pt15.1/
1-1
male/
22m
PBL de novo 47,XY,+mar[10]/
46,XY[18]
inv dup(5)(pterp15.1:
:p15.1
pter)
aCGH: 0-17.65 Mb
wcp; BACs; aCGH see below {59}  
  alternating hypo- and hyperthyroidsm treated until 9m of age; at 11m complex hyerthermal seizures andf hypotonia; at 22m dysmorhic signs noticed
 
  05-
N-pt14/
1-1
female/
1w
AF/
PBL
de novo 47,XX,+mar[19] inv dup(5)(pterp14:
:p14
pter)
(sSMC derived from a paternal chromosome 5)
midi;
all human centromere probe; telomere probe, cep 1/5/19; UPD-test
see below {7; 10; 11; 21}  
Amniocentesis due to severe microretrognatia in ultrasound; delivery was induced in week 37 due to cessation of intrauterine growth; weight <3rd centile, length and HC 3rd centile; APGAR 1/6/7; microretrognatia, cleft hard and soft palate; muscular hypotonia; at 4.5m length, weight and OFC <3rd centile; severely dystrophic, delayed psychomotor development; microcephaly, prominent forehead, telecanthus, upward slanting palpebral fissures, short nose with depressed nasal bridge, prominent philtrum, large and thin ears, thorax asymmetry, left convex scoliosis of thoracic spine, atrial septal defect, epilepsy
                     

 

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  
  05-N-
IMB-p1?/
1-1 to 11-1
8 partial trisomy 5p cases summarized in {23}, 11 in {30} {23, 30}  
  05-N-
IMB-p14/
2-1
46,XX,trp(5)(pterp14::p14p15.33::p15.33qter) {24}  
  05-N-
IMB-q35.1/
1-1
46,XX,inv dup(5)(q35.1qter) {28}