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

- sSMC -

CHROMOSOME 20

References

 

             
  Cases without
clinical findings
14 Cases with
clinical findings
27 symptoms  
  similar imbalances - no clinical findings similar imbalances with clinical findings  
    Cases with
isochromosome 20p
4    
  Cases with
unclear clinical correlation
Cases with
neocentromeres
2 tumor
0
 
      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 20
mat
UPD 20
pat
UPD 20
unclear
 
           

 


the probably non-dosage sensitive pericentric region of chromosome 20


SCHEMATIC CYTOGENETIC DEPICTION

tl_files/tiny_templates/Bilder TL/sSMC/sSMC-20.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] * = case mult 2-39

 

critical region ? --- 22.83* uncritical region [25.70 centromere 28.40] uncritical region 29.93 --- 30.12 critical region

Below adapted for UCSC hg19, 2009

critical region ? --- 24.73* uncritical region [25.60 centromere 29.40] uncritical region 30.52 --- 31.35 critical region

 


Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

20p - proximal 20q - proximal
symptoms
 brain malformations 0 % (67 %)
developmental delay 0 % (33 %)
dysmorphic face 0 % (33 %)
finger or toe/foot malformations 0 % (33 %)
growth retardation (100 %) (67 %)
heart defect (100 %) 0 %
hypotonia 0 % (33 %)
number of cases (marked with “°” below) 1 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  
  20-O-
p12.2/
1-1
male/
prenatal
AF de novo 47,XY,+mar[20%]/
46,XY[80%]
see below
cenM; subcenM; UPD-test healthy child born, normal after 3 months {0}
{42; 47 case 13}
{58}
 
r(20)(::p12.2~12.3q11.1::)[5]/r(20)(::p12.1q11.1::q11.1p12.1::)[2]/min(20)(:p12.1q11.1::q11.1p12.1:)[1]
FISH-data: RP11-96L6 in (25.47MB) on sSMC
  20-O-
p11.23/
1-1
female/
adult
PBL familial 47,XX,+mar[?%]/
46,XX[?%]
mar(20)(p11.23q11.21)
size 6.6 MB
n.a.; subcenM with 3 BACs, array-CGH see below {29} mother of case 21  
Normal female; sSMC detected due to child with mild developmental delay; patient rolled at 7 months of age, crawled at 11 months of age, and pulled to stand and cruised at 12 months of age; patient has a two word vocabulary at 12 months of age; developed seizures at 10 months of age; mild dysmorphic features; normal head MRI. The patient’s mother, two siblings, and maternal grandfather carry the marker in a mosaic state. All family members are phenotypically normal.
  ***
20-O-
p11.21~
11.22/
1-1
***
male/
prenatal
AF
chord blood
de novo 47,XY,+mar[10]/
46,XY[55]
paternal isodisomy
see below cenM, subcenM; UPD-test Amniocentesis due to advanced maternal age; healthy child born at term, normal at 3 months of age {58}  
in AF: min(20)(:p11.22~11.21q11.1:) , in chord blood: min(20)(:p11.22~11.21q11.1:)[8]/ min(20)(:p11.22~11.21q11.1::q11.1p11.22~11.21:)[4]/min(20)(:p11.1q11.21:)[1]
FISH-data: RP11-96L6 in 20p (25.47MB) and  RP11-243J16 in 20q (29.93MB) on sSMC
  20-O-
p11.21/
1-1
female/
34y
PBL de novo 47,XX,+mar[13]/
46,XX[2]
see below M-FISH; subcenM normal phenotype; normal mental development; normal cyclus and normal female habitus, but no children with 2 different partners over 10 years {35} case 96
{43}
{64} case 20-1
 

47 chromosomes:
mar1: min(20)(:20p11.2120q11.21:)[5]/
mar2:min(20)(:20p11.120q11.21:)[1]/
mar3:r(20)(::20p11.120q11.21::)[1]/
mar4:r(20)(::20p11.120q11.21::20p11.120q11.21::)[5]/
mar5: min(20)(:20p11.120q11.21::20p11.2120p11.1:)[7]/
mar6: inv dup(20)(:20p11.120p11.21::20q11.2120p11.1::20p11.120q11.21:
:20p11.2120p11.1:)[1]/
mar7: inv dup(20)(:20q11.120q11.21::20p11.2120q11.1:
:20q11.120p11.21:)[1]/
mar8: inv dup(20)(:20q11.120q11.21: :20p11.2120q11.1::20q11.120p11.1:)[1]
48 chromosomes: mar9: min(20)(:20q11.120p11.21::20q11.2120q11.1:) plus mar4: r(20)(::20p11.120q11.21::20p11.120q11.21::)[1]

FISH-data: RP11-96L6 in (25.47MB) and  RP11-243J16 in (29.93MB) on sSMC
aCGH: 23,152,443-29,852,809 MB

  ***
20-O-
p11.21/
2-1
***
female/
prenatal
AF
chord blood
de novo (?) 47,XX,+mar[43%]/
46,XX[57%]
min(20)(:p11.21q11.21:)*
FISH-data: RP5-1025A1 in 20p (24.96MB) to RP5-867M17 (29.78MB) in 20q
M-FISH
BACs
Amniocentesis due to advanced maternal age; healthy child born, however, with growth retardation and obesity at 4 months of age {46} case 2  
  20-O-
p11.1/
1-1
female/
prenatal
AF de novo 47,XX,+mar[?] min(20)(:p11.1q11.1:) M-FISH; cenM; UPD-test Amniocentesis due to advanced  maternal age; child born without any signs or symptoms {4} case 10  
  20-O-
p11.1/
1-2
female/
prenatal
AF de novo 47,XX,+mar[80%]/
46,XX[20%]
min(20)(:p11.1q11.1:)* FISH with centromeric probes for chrs. 2,  20, X and wcp 20 Amniocentesis due to advanced  maternal age; child born without any signs or symptoms and normal at age of 20 months. {9} case 2
{11} case 35 or 36
 
  20-O-
p11.1/
1-3
female/
adult
PBL n.a. 47,XX,+mar[100%] min(20)(:p11.1q11.1:)* midi female normal; studied due to the birth of a child, which died shortly after birth with a karyotype 92,XXXX,+marx2  {16}  
  20-O-
p11.1/
1-4
male/
prenatal
AF de novo 47,XY,+mar[3]/
46,XY[17]
r(20)(::p11.1q11.1::) cen 20, wcp 20, telomeric probes Amniocentesis due to abnormal triple marker screen; born at term (birth weight: 2,750 g); at 6 m and 4y phenotypically normal. {20} case 1  
  20-O-
p11.1/
2-1
male/
prenatal
AF
PBL (chord-blood)
de novo 47,XY,+r[80%]/
46,XY[20%]
(in chords blood mar only in 9%)
r(20)(:p11.?1q11.?1:)* FISH with centromeric probes for chrs. 2, 18, 20, Y and wcp 20 see below {9} case 1
{11} case 35 or 36
{0} provided by Dr. Manolakis, Athens, Greece
 
Amniocentesis due to advanced maternal age; child born without any signs or symptoms apart from a isolated syndactyly, type I of toes 2 and 3. At age of 20 months and later at 8 years boy normal
  ***
20-O-
p11.1/
3-1
***
female/
42y
PBL n.a. 47,XX,+mar[28]/
46,XX[10]
r(20)(::q11.21p11.1:
:p11.1
q11.21::)
FISH-data: RP11-96L6 in (25.47MB) and  RP11-243J16 in (29.93MB) on sSMC
cenM, subcenM normal female, primary amenorrhea {64} case 20-2  
                     

 

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  
  20-
CO-1
male/
35y
PBL
sperm
maternal
(mother has mar in 3.14% of PBL)
47,XY,+mar[4]/
46,XY[96]
8,25% in sperm
mar(20) centromeric probes normal - but three miscarriages in his wife {23}
{35} case 97
{64} case 20-3
 
  20-
CO-2
male/
35y
PBL
sperm
de novo 47,XY,+mar[80%]/
46,XY[20%]
8,25% in sperm
mar(20).ish (wcp20+,D20Z1+) all centromeric probes; wcp 20 normal but azoospermia {24}
{35} case 98
{64} case 20-4
 
  20-
CO-3
male/
adult
PBL de novo 47,XY,+mar[?100%] mar(20) n.a. normal male ; mar detected due to marker presence in unborn child {27} father of case 77  
                     

 


References

Cases with iso-chromosome 20p (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  
  20-W-
iso
/

1-1
male/
prenatal
AF and PBL de novo 47,XY,+mar[73%]/
46,XY[27%]
at birth sSMC in 30% of PBL;
inv dup(20)(q11.2) array-CGH Osteopenia, osteoporosis, IUGR, DD, strabism, abnormal ears, etc.
{65}
 
  20-W-
iso
/

1-2
female/
prenatal
chord blood de novo 47,XX,+inv dup(20)(q11) wcp 20 multiple defects in sonography; pregnancy terminated {50; 63}  
  20-W-
iso
/

1-3
female/
prenatal
CVS de novo 47,XX,+i(20)(p10) subtel 20pter
multiple defects in sonography; pregnancy terminated {51}  
  20-W-
iso
/

1-4
female/
prenatal
AF?
placenta
de novo 47,XX,+inv dup(20)(q11)[80.3%]/
46,XX[19.7%]
n.a. micrognathia, microcephaly, intrauterine growth retardation; pregnancy terminated {15} case VIIc-6  
                     

 


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  
  20-W-
p13/
1-1
male/
8m
PBL de novo 47,XY,+r[60%]/
46,XY[40%]
(at 3y 65/100 cells in PBL with mar; in buccal mucosa 3 signals with cep 20 in 18% of cells)
r(20)(::p13q1?2::)* all centromeric; telomeric, and probe in 20p12-13 see below {10}  
Uncomplicated pregnancy; weight: 4250g, length: 52cm; umbilical hernia one unilateral hydrocele and restricted mobility of hips; at 8m developmental delay and dysmorphic features like full cheeks, deep-set eyes, slight upslanting palpebral fissures, convergent strabismus of left eye; lipoma at base of nose at age of 14m; mild micrognathia, broad neck and thorax, diastasis recti, clinodactyly of 5th fingers; walking at 23m;
  20-W-
p13/
2-1
moved to 20-W-iso/1-4 {15} case VIIc-6  
  20-W-
p13/
2-2
female/
prenatal
AF n.a. 47,XX,+mar[29]/
46,XX[19]
mar(20)(pterq11.1)
could also be an iso chromosome
aCGH: 2.97-32,13 MB
aCGH sonographic findings - TOP: Dysmorphic
face, thumb anomalies,
agenesis of pancreas tail, bicornate uterus
{57} case 24  
  20-W-
p13/
3-1
moved to 20-U-9 {0}  
  20-W-
p13/
3-2
n.a./
prenatal
AF de novo 47,+mar min(20)(pterq10:) n.a. ultrasound abnormalities, TOP {44} 1 case  
  20-W-
p13/
4-1
see 20-N-pt11.2/1-1 {17-19}  
  20-W-
p13/
5-1 = 5-2
see 20-W-iso/1-2 {50}  
  20-W-
p11.2/
1-1  °
female/
1m (?)
PBL
Fibroblast
de novo 47,XX,+r[67%]/
46,XX[33%]
47,XX,+r[83%]/

46,XX[12%]
r(20)(::p11.2q10::) midi; UPD-test see below {5} case N  
born during pregnancy week 38 with growth retardation, weight 1,940 g, length 45 cm; marked feeding problems, poor weight gain, no malformations other than a small ASD. At 30 m she developed normally, but she was still very small and had feeding difficulties.
  20-W-
p11.23/
1-1
female/
prenatal
AF de novo 47,XX,+mar[54%]/
46,XX[46%]
r(20)(::p11.23q11.22::)
FISH-data: RP5-1096J16 in 20p (20.19MB) to RP11-353C18 in 20q (33.83MB)
M-FISH;
BACs
see below {46} case 1  
Amniocentesis due to intrauterine growth retardation (week 22); TOP at 34 weeks; weight was 1,630 g (5th centile), height 43 cm (10th centile), and occipitofrontal circumference (OFC) 27.5 cm (<5th centile). Moderate craniofacial dysmorphism, including elongated skull with a shelf, a broad nose, a bilateral crease below the lower eyelids, microretrognatia, normally implanted but abnormal ears, and a slight nuchal edema. Hands, feet, and genitalia were normal. Internal examination showed no anomaly. Skeletal X-rays were normal.
  20-W-
p11.22/
1-1
female/
1.5 y
PBL n.a. 47,XX,+mar[18]/
46,XX[9]
min(20)(:p11.22~11.21
q11.21:)
FISH: 25.47 and 29.92
aCGH: 24.70-25.70
centromeric probes; subcenM;
array-CGH
Developmental delay, lipoma of the corpus callosum, hypotonia, VSD, ASDII {56} case Sm-10  
  20-W-
p11.22/
1-2
female/
4y
PBL
(EKF-
cellbank)
de novo 47,XX,+mar[7]/
46,XX[4]
min(20)(:p11.22~11.21
q11.21~11.22:)
cenM; subcenM; UPD-test see below {0} provided by Dr. Aniko Ujfalusi Hungary  
Born after uneventful pregnancy, 38th week of gestation (2850g weight). Long bones were reported as shortened at birth; suggestion of hypochondroplasia, parents also small (~160cm).
At 4y: height: 91.8cm (<3 centile), Weight: 15.4 kg (10.-25. centile). Breathing through mouth, speech is slurred, and poor in vocabulary. Macrocephaly, slightly reclined neck, short long bones, strong suborbital skin fold, flat nasal root. Intelligence borderline (60-70).
  20-W-
p11.22/
2-1 °
female/
postnatal
PBL de novo 47,XX,+mar[100%] min(20)(:p11.2?2q11.1:) cenM; subcenM see below {0} provided by Dr. J. Vermeesch,
Leuven, Belgium
 
Developmental delay and facial dysmorphism. Hypotelorism and macrocephaly
  20-W-
p11.21/
1-1
male/
8y
PBL n.a. 47,XY,+mar[%?]/
46,XY[%?]
min(20)(:p11.21q11.21:) cenM; subcenM see below {37}case 31  
congenital malformations, born at term, heart defect suspected, weight 4010g, length 52cm, at 8y mild motor development delay, muscular hypertonia, dystonia; at 7 years: weight 26 kg, length 127cm, OFC=55cm, macrocephaly (borderline), dolichocephaly, prognathia, large alveolar ridge, brain: dilated lateral ventricles (moderate), low-set dysplastic ears, epicanthus, short wide nose, short philtrum, arched palate; small umbilical hernia, polythelia, short neck, speech dysarthria
  20-W-
p11.21/
2-1
n.a./
postnatal
PBL de novo 47,+mar[75%]/
46[25%]
mar(20)(:p11.21q11.21:)
size 1.9 MB
n.a.; subcenM with 3 BACs, array-CGH Psychomotor delay {29} case 22  
  20-W-
p11.21/
3-1
female/
prenatal
AF de novo 47,XX,+mar[12]/
46,XX[10]
r(20)(::p11.21q11.23:)
size 10.8 MB; breaks in positions 24.17MB and 36.44MB
wcp probes; array-CGH see below {45}
{57} case 23
 
Amniocentesis due to a Turner syndrome in previous pregnancy; normal sonography; TOP in week 24; postmortem examination: weight 670g (50th centile); length 32 cm (25th centile); OFC 22.5cm (50t centile), dysmorphism: high forehead with frontal bossing, voluminous ocular globes, hypertelorism, low set ears with hypoplastic helix, wide flat nasal bridge, long smooth philtrum, thin upper lip, microretrognatia, hypoplastic labia and clitoris, rocker bottom feet;
20-W-
p11.21/
4-1
female/
prenatal
AF de novo 47,XX,+mar[40%]/46,XX[60%]  - 47,XX,+20 in chorion min(20)(:p11.21q11.22:)
aCGH (hg19): 25.4-34.15 Mb
cenM
subcenM UPD-test aCGH
abnormal phenotype {0} provided by Dr. Manolakis, Athens Greece
  20-W-
p11.1/
1-1
female/
prenatal
AF/
PBL
(EKF-
cellbank)
de novo 47,XX,+mar[20] see below cenM
subcenM
see below
{2} case 10  
child born, at age of 2 retardation in speech development; weak ear dysmorphism and slight clinodactyly of 5th finger
min(20)(:p11.1q11.1:) {cenM}
47,XX,+min(20)(:p11.1
q11.22:)[18]/47,XX,+min(20)(:q11.22p11.1::p11.1q11.22:)[7]/
47,XX,+r(20)(::p11.1
q11.22::p11.1q11.22::)[3]/46,XX[2] {subcenM}
  20-W-
p11.1/
2-1
moved to 20-U-10 {3, 58}  
  20-W-
p11.1/
3-1
female/
18y
PBL n.a. 47,XX,+mar[100%] min(20)(:p11.1q11.1:)* different FISH probes, micro satellite analysis; UPD-test see below {12} case 4  
Female studied due to primary amenorrhea, hirsutism, mild mental retardation; myopic retinal degeneration, horizontal nystagmus, no uterus and abnormal  ostium of urethra in the bladder.
  ***
20-W-

p11.1/
4-1 °
***
female/
newborn
AF/
PBL
de novo 47,XX,+mar[100%] min(20)(:p11.1q11.21:)
array (hg19):
29.63-31.35 MB
aCGH; cep 20 see below {0} provided by Dr. L. Rodriguez, AbaCid, Madrid, Spain.  
Normal pregnancy but with oligoamnios and IUGR since 32th gestational week. At birth weight of 2050 g; OFC: 32 cm, length: 43.5 cm all values (<3. centile) and hypotonic. No gain of weight for 2 months; then an intrathoracic stomach with duodenal bulb infradiaphragmatic, a light colpocephaly and corpus callosum hypoplasia was detected; after surgery good evolution, getting oral alimentation.
  20-W-
p11.1/
4-2 °
female/
2m
PBL de novo 47,XX,+mar[100%] min(20)(:p11.1q11.21:) aCGH, FISH see below
{33}  
  birth weight, OFC and lenght >3. centile; intrathoracic stomach with duodenal bulb infradiaphragmatic, a light colpocephaly and corpus callosum hypoplasia were diagnosed. After surgery she is having good evolution, getting oral alimentation and at 4 months old she weights 4110 gr.  
  20-W-
p11.1/
5-1
male/
prenatal
AF and PBL n.a. 47,XY,+mar[100%] min(20)(:p11.1q11.23:)[5]/min(20)(:p11.1q11.23::q11.23p11.1:)[1]
arr hg19: 29.8-37.5 MB
cenM, subcenM, aCGH see below {0} provided by Dr. Zvi Borochowitz; Israel  
  AMA, at 1 y: sparse scalp hair, high forehead, low set ears, protruding ears, long philtrum, nystagmus, upturned nares, tubular fingers, broad thumbs and toes, clinodactyly of V finger. global mental retardation and dysmorphic features  
  20-W-
p10/
1-1
male/
1m
PBL de novo 47,XY,+mar[48%]/
46,XY[52%]
r(20)(::p10q12:
:q13.2
q13.33::)
midi see below {5} case O
{6} case E
{14} case 24
 
Birth weight: 3510g, length: 48cm; mental retardation, behavioral problems, low-set ears, and restricted mobility in the hips.
                     

 

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  
  20-W-
IMB-
p12.1/
1-1
n.a./
n.a.
PBL de novo 46,dup(p11.2p12.1)/46 n.a. see below {32}  
Sotos syndrome (cerebral gigantism)
  20-W-
IMB-
p11.23/
1-1
male and female/
n.a.
PBL familial 46,dup(p11.21p11.23) n.a. see below {33}  
Alagille syndrome (arteriohepatic dysplasia, AHD) without liver involvement
  20-W-
IMB-
q11.1/
1-1
male/
2m
PBL de novo 46,XY,dup(20)(q11.1q12)
RP1184++,RP11-382A12++
wcp 20, MCB, BACs see below {28}  
facial dysmorphism = prominent metopic suture, epicanthic fold, peripalpebral edema, small and thick ears, prominent cheeks; walking with 25m, speech delay; at 3y no growth abnormalities.
  20-W-
IMB-
q11.2/
1-1
male/
16m
PBL n.a. 46,XY,dup(20)(q11.2q12) wcp 20, BACs see below {34}  
psychomotor retardation, craniofacial anomalies and severe vision deficit.
                   


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  
  20-
CW-1
male/
2y
PBL de novo 48,XY,+mar x2[28%]/
47,XY,+mar[72%]
r(20) FISH with all available centromeric probes see below {7} case 10  
dysmorphic features like scaphocephaly, high pitched voice, high palate, clinodactyly of fingers 2, 4 and 5 towards the 3rd finger, short stature
  20-
CW-2
male/
2y 8m
PBL de novo 47,XY,+r[25%]/
46,XY[75%]
r(20) FISH with all available wcp probes see below {13}  
Normal pregnancy, born in 39th week, weight, length and OFC normal, APGAR 9/9/-; at 2y8m psychomotor retardation, facial abnormalities, brachyturricephaly, normal set ears with lobe crease, high arched palate, short neck, bilateral clinodactyly of 5th finger; both testes in inguinal canal.
  20-
CW-3
male/
prenatal
CH/PBL/
fibroblast
de novo 47,XY,+mar[16-87%]/
46,XY[6-31%]
+20 cell line absent in PBL; mar present in all studied tissues
r(20) ish. (cep20+; wcp20+) different FISH probes: wcp20; cep20 see below {8}  
CVS due to advanced maternal age; born at 35 weeks' gestation following preterm prenatal. rupture of membranes. APGAR score 2/6/8; Birth weight 1730 g (10. percentile) length 44.5 cm; Noted at birth: asymmetric, triangular face; prominent forehead; bulbous nose with slightly upturned tip; hypoplastic and short philtrum; small mouth; high palate; micrognathia; retrognathia; large, flat, and simple ears; redundant skin on neck, chin, and upper shoulders; blind shallow sacral dimple; proximally placed thumbs which folded over the palms; clinodactyly of the second, fourth, and fifth fingers; feet held in eversion, prominent heels; wide space between the first and second toes; proximally placed fifth toes; hypotonia; increased skin elasticity; and hyperextensible joints.
At 34 m: failure to thrive, dysfunctional swallowing, and generalized hypotonia; gross motor development delayed, but fine motor coordination, expressive language, and problem solving were appropriate for age. On follow-up at 13 months, the patient's weight was 6730 g (5. percentile) and height was 68'5 cm (5. percentile); percutaneous gastrostomy tube for feeding. At 16 m, weight 8230 g (3. percentile); height 70,8 cm (3. percentile) still required gastrostomy tube feedings.
  20-
CW-4
male/
2.5y
PBL de novo 48,XY,+rx2[4%]/
47,XY,+r[71%]/
46,XY[25%]
r(20) ish. (cep20+; wcp20+) FISH with centromeric probes for chrs. 2, 20, Y and wcp 20 see below {9} case 3
{11} case 34
 
Global delayed development in gross motor, fine motor, speech and social skills, height and weight below 3rd centile, heart defect, hypertelorism, depressed root of nose, low-set ears, bilateral plantar furrow (1, 2), clubbed fingers
  20-
CW-5
male/
14m
PBL maternal
mother:
47,XX,+r(20)[8]/
46, XX[42]
47,XY,+r(20)[skin 11 - blood 25]/
46, XY[skin 14 - blood 37]
r(20) ish. (cep20+; wcp20+) FISH with wcp 20 see below {26}  
At 14 m developmental delay and some dysmorphic features. Born at 39 weeks gestation after uncomplicated pregnancy; at birth small and broad hands and feet as well as low set ears were noted. At 14 months coarse round facies, full cheeks, slight upslanted palpebral fissures, convergent strabismus, micrognathia, high and narrow palate, low set ears, brachycephaly, broad neck and chest, pectus excavatum, widely spaced nipples and normal external genitalia. He had broad and short hands and feet, brachydacyly of fingers and toes, as well as 2nd/3rd syndactyly and clinodactyly of 5th fingers. Neurological examination normal. Developmental delay with poor social contact. Radiologic studies confirmed brachycephaly, short hands showing coarse metacarpal bones, slight platyspondyly and mild generalized osteoporosis.
The mother had a borderline IQ, a coarse facies with upslanting palpebral fissures and broad nose with hypoplastic nares. She had a short neck, asymmetric thorax with rib retraction and hypoplasia on the left side, with lowering of left shoulder. There was a slight pectus excavatum and hypoplasia of the pectorals muscle. The radiological studies confirmed the described skeletal anomalies, as well as platyspondyly. The father was normal.
  20-
CW-6
male/
prenatal
AF de novo 48,XY,+mar[11]/
47,XY,+mar[4]
mar(20) n.a. see below {27} case 75  
Advanced maternal age; positive maternal marker serum screen; child born and at 1y developmental delay and dysmorphic features
  20-
CW-7
n.a./
prenatal
AF de novo 47,+mar[?%] r(20) n.a. abnormal sonography; TOP {44} 1 case  
  20-
CW-8
female/
2y
PBL de novo 47,XX,+mar[?100%] min(20) cep probes short stature, minor dysmorphic features and global developmental delay {49}  
  20-
CW-9
n.a./
10y
PBL n.a. 47,+mar[100%] min(20) SKY DD, autism {52} case F0549359  
  20-
CW-10
female/
8y
PBL n.a. 47,XX,+mar[?%]/
46,XX,[?%]
min(20) SKY DD, MR, trigonocephaly {52} case F0819257  
                     

 


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  
  20-
U-1
see mult 2-6
{1} case 34  
  20-
U-2
female/
12y
PBL/
Fibro
n.a. 46,X,+mar[15]/
46,XX[35]
Skin fibroblasts: mar in 35 of 50 cells
mar(20).ish (D20Z1+) different centromeric probes; telomeric probe see below {25}  
Normal pregnancy; born at term by cesarean section due to failure to progress. The parents reported: always delayed in all areas: first walked at 2y, at 4y vocabulary of about 20 words. At 12y able to bath herself, make her bed and wash dishes; was in special classes; behavioral evaluation concluded that she had pervasive developmental delay with mild to moderate autism. MRI showed decreased brain volume on the left; an NMRI of the spine revealed extrusion of the L3-4 as well as a bulge at the L5 level. An MRI of the abdomen demonstrated a right atretic kidney. The parents reported episodes of sleep apnea at night and a sleep study did reveal short episodes of central sleep apnea, with an average duration of 12 s and no desaturations. Physical exam: height 125.4 cm (<5%); weight 38.8 kg (25%); head circumference 50 cm (10%); down-slanting palpebral features with right-sided facial microsomia, right ear slightly over-folded.
  20-
U-3
female/
prenatal
AF de novo 47,XX,+mar[?%]/
46,XX[?%]
r(20)(::p13q13.32::)[7]/
r(20)(::p13
q13.32:
:p13
q13.32::)[1]
cenM;
subcenM, MCB
advanced maternal age; TOP {0} provided by Dr. Mazauric, Düsseldorf, Germany  
  20-
U-4
male/
prenatal
AF de novo 47,XY,+mar[100%] mar(20) n.a. advanced maternal age; TOP {27} case 76  
  20-
U-5
male/
prenatal
AF n.a. 47,XY,+mar[20]/
46,XY[3]
r(20)(::q11.21q13.12::) n.a. advanced maternal age; Half of twin with the other fetus being carrier of a mar(20)(investigated elsewhere) {48} case 20  
  20-
U-6
male/
prenatal
AF n.a. 47,XY,+mar[100%] min(20)(:p11.21q11.21:) cenM, subcenM n.a. {0} provided by Dr. Alves, Porto, Portugal  
  20-
U-7
female/
prenatal
AF n.a. 47,XX,+mar[100%] min(20)(:p11.1q11.1:) cenM, subcenM n.a. {0} provided by Dr. Alves, Porto, Portugal  
  20-
U-8
moved to 20-W-p11.1/5-1 {0} provided by Dr. Zivi Borochowitz; Israel  
  20-
U-9
male/
1m
PBL de novo 47,XY,+mar[100%] min(20)(pterq11.1:)
maternal UPD 20
centromeric probes, subcenM, MCB; UPD-test see below {0}  
born at 36 weeks gestation; birth weight - 1.92kg; at birth - plagiocephaly; micrognathia; long philtrum; high arched palate; low set ears; slightly widened bulbar fingers; slightly prominent occiput and prominent forehead; right inguinal hernia; inverted nipples; hypospadias; torticollis; a heart scan at 3m showed 4 VSDs and a PFO. He also suffers from gastroesophagial reflux; mild optic nerve hypoplasia, nystagmus and some asymmetric opsoclonus - more in the left eye than right eye. MRI brain scan in at 10m of age revealed a wide range of craniocerebral abnormalities, neurodevelopment delay; dysplastic inner ear on left side and cerebellar tonsillar ectopia through the foramen magnum. At 1y he was operated on to lower his left un-descended testicle. Spine MRI and X-rays at 13m showed scoliosis. At 16m still unable to sit unaided and now had gaiters for his legs. Feeding problems after birth and was fed via an NG tube until 1y when a gastrosomy PEG was introduced. At 15m weight 7.22kg.
  20-
U-10
male/
4y
PBL de novo 47,XY,+mar[20]/
46,XY[28]
min(20)(:p11.1q11.1:)
maternal UPD 20
midi; UPD-test see below {3, 58}  
growth retardation; minor facial dysmorphic features; hyperactive; mother at age of conception 40y; intra-uterine growth retardation
  20-
U-11
male/
prenatal
AF n.a. 47,XY,+mar[90%]/
46,XY[10%]
r(20)(::p11.1q11.2::)[10]/min(20)(:p11.1q11.2:)[2]
FISH-result for break in long arm: between 38.11 and 46.72 MB
wcps, subcenM, PCL-FISH
 
postnatal bilatheral sensorineural hearing loss {54} case 21  
  20-
U-12
female/
prenatal
AF/ PBL de novo in AF - 46,XX[15]
in PBL: 47,XXX[2]/
47,XX,+mar[17]/
46,XX[2]
mar(20)(:p11.1q11.21::)
aCGH cen20 to 32.09 MB
besides: der(20)del(20)(p12.2p12.2)dup(20)(p12.2p12.1
FISH; aCGH congenital heart defect, preauricular tags, growth retardation {55} case 9  
  20-
U-13
male/
prenatal
AF de novo 47,XY,+20[3]/
47,XY,+mar[14]/
46,XY[3]
min(20)(:p12~13q11.1:) subcenM plexuscysts, cleft lip and palate {0} provided by Dr. Mitulla, Suhl  
  20-
U-14
n.a./
postnatal
PBL n.a. 47,XN,+mar[?%] r(20) FISH n.a. {60} 1 case  
  20-
U-15
female/
prenatal
CVS de novo 47,XX,+mar[100%] min(20)(:p11.21q12:)
aCGH: 24.82-37.14 MB

aCGH AMA, n.a. {62} case CVS-1  
  20-
U-16
male/
1.5 y
PBL de novo 47,XY,+mar[13]/
46,XY[7]
mar(20)(p12.2q11.21)
aCGH: 10.61-29.64 Mb
UPD(20)mat
aCGH dysmorph, DD, cleft palate, growth retardation, frontal bossing {66}  
                     

 


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  
  20-N-
pt11.2/
1-1
female/
3y
PBL; fibroblasts de novo 47,XX,del(20)(qter→p11.2:),+inv dup(20p)[100%] inv dup(20)(pterp11.2:
:p11.2
pter)
pan- centromeric probe; various FISH-probes for #20 see below {21; 22; 30; 31}  
postnatal: congenital heart disease (VSD), minor anomalies; pulmonary atresia; at 3.1 y mild brachycephaly; height and weight an 90-97th centile; OFC on 75th centile; epicanthic folds, long philtrum, both hands slightly stubby; clinodactyly of 5th finger; mild developmental delay; died at 5y for unclear reasons.
  20-N-
qt13.33/
1-1
n.a./
postnatal
PBL de novo 47,XN,+mar[?%] inv dup(20)(qterq13.33:
:q13.33
qter)
array-CGH mental retardation
{59; 62}  
                     

 

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  
  20-N-
IMB-
pter/
1-1 to
mult
see {40} {40}  
  20-N-
IMB-
p12/
1-1
to 1-2
see {38-39} {38-39}  
  20-N-
IMB-
p13/
1-1
female/
13m
PBL maternal
ins(20)(p13q11.21q13.33)
46,XX,rec(20)dup(20p)dir ins(20)(p13q11.21q13.33)mat BAC-FISH see below {36}  
At birth 3,000 g (full term pregnancy); generalized tonic seizures at ages 1, 3, and 13 months that were controlled with Phenobarbital. Discrete facial dysmorphism with large forehead, mild hypertelorism, long prominent nose, short upper lip, and dysplastic ears but no trigonocephaly or microcephaly; anterior anal placement and asymmetric thigh folds, mild ataxia, psychomotor development delay.
  20-N-
IMB-
qter/
1-1 to
mult
see {41} {41}