FISH

SMALL SUPERNUMERARY MARKER CHROMOSOMES

- sSMC 13 -

           References

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 13   maternal   paternal   unclear


the probably non-dosage sensitive pericentric region of chromosome 13

 


SCHEMATIC CYTOGENETIC DEPICTION                    
 sSMC-13 DISCLAIMER

 


 

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]

 [p-tel ---   centromere 18.40]   uncritical region 19.31 --- 22.29 critical region

Below adapted for UCSC hg19, 2009

 [p-tel ---   centromere 19.50]   uncritical region 20.41 --- 23.42 critical region

 DISCLAIMER

 


 Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

13q - proximal

symptoms

brain malformations

(100 %)

obesity

(100 %)

scoliosis

(100 %)
number of cases (marked with “°” below) 1

 


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  
  ***
13-O-

q11.2/
1-1
***
female/
prenatal
AF de novo 47,XX,+mar[100%]
in PBL  sSMC only in 8/30 lymphocytes
min(13)(pterq11.2:)
FISH-data: present at least up to 19.31 MB
cenM; subcenM Advanced maternal age; normal child at 10 months of age {0} provided by Dr. Sagi, Jerusalem, Israel  
  13-O-
q12.2/
1-1
female/
prenatal
AF/ PBL de novo 47,XX,der(13),+mar[100%] 47,XX,dic(13)(pterq12.2:
:p11.2
qter),
+min(13)(pter
q12.2:
:p1?2
pter)
cep probes, subcenM Aberrant first trimester screening, normal child born and normal at 1 y {0} provided by Dr. Prager and Junge, Dresden, Germany  
                     

 

 


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  
  13-W-
q12.12/
1-1
female/
postnatal
PBL? n.a. 47,XX,+mar[100%] min(13)(pterq11.12:) array-CGH abnormal {43} case 27105  
  ***
13-W-
q12.12/
1-2  °
***
female/
11y
PBL? n.a. 47,XX,+mar[100%] min(13)(pterq12.12:)
aCGH: break in 22.29 MB
different FISH-probes; array-CGH Agenesis of the corpus callosum, scoliosis, sleep apnea, obesity {50} case 8  
  13-W-
q13.2/
1-1
n.a./
prenatal
AF de novo 47,+mar[100%] mar(13)(pterq13.2:)*
size ~14MB = position 32.40
n.a.; subcenM with 3 BACs see below {24} case 14  
Multiple anomalies noted on prenatal ultrasound, including diaphragmatic hernia, open neural tube defect, micromelia, abnormal skull, and single umbilical artery; pregnancy terminated.
                     

 

 

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  
  13-W-
IMB-
q12/
1-1 to
1-5
female and male/
postnatal
PBL maternal (balanced translocations) der(13)t(13;div. chrs.)(q12;div. breakpoints) n.a. see below {32-37}
reviewed in {38}
 
features in common: short stature, microcephaly, dysplastic ears, strabismus, epicanthic folds, down slanting palpebral fissures, short mandible, mental retardation form mild to severe.
  13-W-
IMB-
q13/
1-1 to
1-2
female and male/
postnatal
PBL maternal (balanced translocations) der(13)t(13;div. chrs.)(q13;div. breakpoints) n.a. similar to 13-W-IMB-q12 cases {37; 39}
reviewed in {38}
 
                   

 

 


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  
  13-
U-1
female/
10m
PBL de novo 47,XX,inv dup(13)(qter→q21::q21→qter),+del(13)(q21)[100%] del(13)(q21) probes as specified in {9}  see below  {8} case 13b
{9; 12}
 

low birth weight, brachycephaly, microcephaly, thick eyebrows and curly eyelashes, bil. microphtalmia, developmental delay, bil. postaxial polydactyly

  13-
U-2
male/
1w
PBL de novo 47,XY,inv dup(13)(qter→q14.1::
q14.1→qter), +mar1[75%]/
47,XY,inv dup(13)(qter→q14::q14→qter), +mar2[25%]
mar1 = r(13)(::p13q14.1::)
mar2 = r(13)'
(::p13
q14.1: :p13q14.1::)
RB1 probe; probe in 13q32-q33; cep13/21;  see below  {5; 12; 25}
{8} case 13a
 

normal birth and delivery; weight at 25. centile, flat philtrum, slightly protuberant ears, capillary hemangiomas on forearm, hypospadias, hypotonic; at 4m HC at 25. centile, length at 75. centile, interpupillary distance at 85. centile; bilateral congenital glaucoma, bilateral retinoblastoma, no hearing at right ear, developmental delay at 17m; 

  13-
U-3
see mult 2-2 {1}  
  13-
U-4
chimera/
prenatal
skin fibroblasts maternal
mother has 48,XX,+mar 2x
chi46,XYpat[18]/47,XX,+mar1[8] inv dup(13) FISH - probes not specified see below {1}  

Twin A - placenta grossly enlarged and cystic, low amniocytes fluid, poor growth; at 15 w spontaneous abortion; second twin was normal, but also aborted.

  13-
U-5
to U-6
male and
female/
n.a.
n.a. de novo 47,+mar[100%] mar(13) wcp13 n.a. {186}cases 23-24  
  13-
U-7
male/
child
n.a. n.a. 47,XY,+mar[40]/
46,XY[10]
min(13)(pterq12.1:) cenM; subcenM n.a. {0}case provided by Dr. Saigi, Israel  
  13-
U-8
male/
6y
PBL maternal
balanced translocation
47,XY,+mar[100%] der(13)t(8;13)
(p23.1;q12.11)
array-CGH:
chr. 8: 0-7.09 MB
chr. 13:17.92-21.81 MB
cenM; subcenM, midi, subtel 8p, array-CGH see below {53} case Sc-1, {54}
 

mental retardation, general developmental delay, severe retardation in language development; no family history; 6 healthy sisters and brothers

  13-
U-9
see mult 2-26 {0} case provided by Dr. Michal Sagai, Israel  
  13-
U-10
male/
2y
PBL de novo

48,XY,+mar1,+mar2[20]

min(13)(qterq33.3:
:p12
q12.12:)
mar 2 not defined
array CGH, BACs acc. to {28} see below {28}case 2  

moderate global developmental delay, bilateral anterior segment dysgenesis of the eye in the form of the Axenfeld-Rieger anomaly, macrocephaly, past history of bilateral inguinal hernias, and several depigmented maculae. An MRI was significant for a short, thick corpus callosum, prominent perivascular spaces with thinning of the gray matter, and an enlarged posterior fossa. 

  13-
U-11
n.a./
n.a.
n.a. n.a. 47,+mar[?%] mar(13) wcp probes no info available {45} 1 case  
  13-
U-12
male/
adult
PBL n.a. 48,XY,+21,+mar[1]/ 47,XY,+21[29] r(13)(::p1?2q1?3::)[1]/
der(13(pter
q?12.11:
:p11.1
q1?3:
:q11.1
p1?1.2:)[2]
cenM, subcenM Down syndrome {0} provided by Dr. Brecevic, Zagreb, Croatia  
  13-
U-13
female/
prenatal
AF de novo 47,XX,+mar[100%]

min(13)(:p12q12.1:)[3]/r(13)(::p12q12.1::)[7]
aCGH: no euchromatin detected

cenM, subcenM
aCGH
no info available {0} provided by Dr. Müller-Navia, Mainz, Germany  
  13-
U-14
female/
prenatal
AF maternal
balanced translocation
47,XX,+mar[100%] der(13)t(4;13)(q31.3;q13) n.a. MLPA sonographic abnormalities (polyhydramnion, unilateral hydrothorax) {47} case 7; {54}
 
  13-
U-15
female/
prenatal
CH; AF n.a. CH: 47,XX,+13[12]/ 47,XX,+mar[8]/
46,XX[30]
in AF: 47,XX,+13[70%]/
46,XX[30%]
inv dup(13)(q12.11) subcenM sonographic abnormalities pointing towards trisomy 13; TOP {0} provided by Dr. Petersen, Athens, Greece  
  13-
U-16
female/
newborn
PBL n.a. 47,XX,+mar[100%] der(13)t(1;13)(q32;q12)
array-CGH:
chr. 1: 208.03 to qter
chr. 13: pter to 24.40 Mb
aCGH different health problems and developmental delay {54}  
                     


 


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  
  13-
N-1
n.a./
prenatal
AF de novo 47,+mar[100%] inv dup(13)(qter) wcp nuchal translucency and measurements above 90th centile. TOP, no further information available {31}   
  13-N-
q12.3/
1-1
see McCl-13-N-q12.3/1-1   {48}   
  13-N-
qt21/
1-1
female/
prenatal
AF de novo 47,XX,+mar[3]/
46,XX[36]
inv dup(13)(qterq21: :q21qter)
sSMC derived from maternal chromosome 13
 
wcp 13, QF-PCR TOP; round facies, hypertelorism, down-slanting palpebral fissures and a bifid nasal bridge. {49; 52}  
  13-N-
q21.31/
1-1
see McCl-13-N-q21.31/1-1   {3; 16; 25; 26; 42}   
  13-N-
qt21.33/
1-1
male/
prenatal/ newborn
PBL/
AF
skin
n.a.

47,XY,+mar[2%]/
46,XY[98%]
in AF: 13/64 cells +mar
in skin: ~50%

min or mar(13)(:q21qter) SNP aCGH AMA, postnatal: diffuse hypomelanotic streaks on skin, otherwise normal at 3.5 y {55} case 1  
  13-N-
qt31/
1-1
female/
4y
PBL de novo 47,XX,+mar[54%]/
46,XX[46%]
inv dup(13)(qterq31: :q31qter) different FISH probes as specified in {4} see below {4} case 1; {12}
{14; 16; 25; 27}
 
at birth weight and OFC <3. centile; at 4y OFC normal but weight at 97. centile; additionally mild convergent strabismus, bitemporal narrowing, hypertelorism, clinodactyly 5. finger; 2/3 syndactyly of feet.
  13-N-
qt31/
1-2
male/
4y
PBL de novo 47,XY,+mar[60%]/
46,XY[40%]
inv dup(13)(qterq31: :q31qter) midi; different FISH probes as specified in {8} see below {8} case 13e
{10} case 2; {12; 16; 44}
 
normal growth, thick eyebrows and hypertelorism, strabismus, deformed lobes, mild mental retardation ; seizures; excess teeth; PDA; diaphragmic hernia, bronchial anomalies, intestinal malrotation, scoliosis, hypospadias
  13-N-
qt31/
1-3
female/
7y
PBL/
skin fibroblasts
de novo blood and fibro: 47,XX,+mar[13%]/
46,XX[87%]
inv dup(13)(qterq31: :q31qter) all centromeric probes; cosmids for 13q14.2, 13q32-33, 13qtel; CGH see below {13; 16; 25}  
born at 36 weeks gestation after a normal pregnancy; weight 2.9 kg, treated for jaundice with 1 day of phototherapy; mild motor developmental delay. She sat at 8months, crawled at 10 months, stood up at 1 year, and walked at 18 months. She was able to say ‘‘mummy’’ and ‘‘daddy’’ at 9 months, and knew a series of words at 18 months. At 7y presence of soft dysmorphic features, concerns about her behavior and progress at school, torticollis present from birth, reported but unconfirmed left-sided hearing loss and parentally-described hyperactivity at school. Previous dental examination had revealed the presence of a complete extra set of teeth. At school, she interacted well with the other children and was in the correct year for her age, but did have extra lessons for mathematics and reading. On examination, her occipitofrontal circumference was 54 cm (98th centile), her weight was 32 kg (90th centile), and height 128.2 cm (75-90th centile). She had bilateral epicanthic folds, a long smooth philtrum, a large fleshy left earlobe, and right torticollis. She was noted to be asymmetrical and her right arm diameter was 1 cm larger than the left. She also had pes planus. There was no evidence of any neurological deficit and her gait was normal. Following she developed episodes reminiscent of absence seizures. During these episodes she was noted to stare vacantly into space for up to a minute. The EEG showed generalized spike and slow wave discharges confirming primary generalized epilepsy. She was started on sodium valproate. Investigations showed that she had small thoracic ribs bilaterally. A renal ultrasound was normal.
  13-N-
qt31/
1-4
female/
prenatal
AF/ PBL de novo 47,+mar[?%]/
46[?%]
inv dup(13)(qterq31: :q31qter) CGH, cep probes, wcp probes, subtelomere probes see below {18, 20, 21, 30}  
amniocentesis in week 24 due to suspect ultrasound with large cisterna magna, no renal differentiation, hypotelorism and ventriculomegaly; TOP; autopsy confirmed facial dysmorphism and renal dysplasia
  13-N-
qt31/
1-5
male/
3m
PBL de novo 47,XY,+mar[100%] inv dup(13)(qterq22.3~31.1: :q22.3~31.1qter) M-FISH subtelomere probes; MCB see below {23}case Neo #13-6  
Born at term by cesarean section after uneventful pregnancy. Birth weight 3600 g, birth length 49 cm. At 3-months developmental delay, poor sucking; weight 5660g (25-50th centile), length 62 cm (25-50th centile) head of circumference (OFC) 40.3 cm (25-50th centile); Hemangiomas in frontal region, pit on right ear helix, hypertelorism, left epicanthal fold, broad and flat nasal bridge, bulbous nasal tip, anteverted nares, long philtrum, mild micrognathia, wide anterior fontanel, broad thumbs, toe syndactyly. Abdominal ultrasonography and echocardiography were normal; cranial CT → Dandy-Walker variant, arachnoid cyst at temporal lobe posteromedial region, porencephaly at left caudate nucleus and frontal white matter; cerebellar vermis dysplasia: broad fourth ventricle, mega cisternae magna, mild cortical cerebral atrophy. Cerebral mild dysmyelinization.
  13-N-
q31.1/
1-1
see McCl-13-N-q31.1/1-1   {15; 25}  
  13-N-
qt31.1/
2-1
male/
prenatal
AF de novo 47,XY,+mar[100%] inv dup(13)(qterq31.1: :q31.1qter)
array: size 32.9 MB
arrayCGH see below  {51}  
at 12 weeks estimated gestational age (EGA) cystic hygroma and IUGR; At 14 and 17 weeks EGA still IUGR, short long bones, persistant cystic hygroma, mega cisterna, cerebellar hypoplasia, hyperechogenic and large kidneys. TOP at 17 weeks EGA. Pathology showed weight 159 g (~50th centile), length 20 cm(~50th centile), and OFC 12.5 cm(~10th centile), cranio-facial dysmorphy with a ‘‘V’’-shaped metopic suture, deep-set eyes, shortflattened nose, small and low-set ears, short buccal frenulum, cystic cervical hygroma, as well as postaxial polydactyly of the right hand and left foot with short fingers, micropenis with hypospadias.
  13-N-
qt31.3/
1-1
n.a./
prenatal
AF de novo 47,+mar[100%] inv dup(13)(qterq31.3: :q31.3qter)
array: size 24.2 MB
arrayCGH see below  {45}  
in week 19 of gestation in sonography: enlarged stomach, postaxial polydactyly, increased nuchal translucency; TOP
  13-N-
qt31.3/
1-2
male/
15y
PBL de novo 47,XY,+mar[8]/
46,XY[12]
inv dup(13)(qterq31.3: :q31.3qter)
array:
93.37 to qter; besides dup 15q13.3 de novo
different FISH-probes; arrayCGH Seizures, cleft palate, and learning difficulties {50} case 12  
  13-N-
qt32/
1-1
female/
1d
PBL/
fibroblasts
de novo 47,XX,+mar[98%]/
46,XX[2%]
(sSMC in fibroblasts 8%)
inv dup(13)(qterq32: :q32qter) alpha-, beta-satellite satIII, telomeric , all wcp , YAC-probes (not specified) see below  {2} case 4
{6}
{8} case 13f
{11; 12; 16; 25; 44}
 
at birth agenesis of right eye, microphtalmia of left eye, microcephaly, scaphocephaly; bulbous nose, short neck, congenital heart defect; agenesis of corpus callosum, 11 ribs; profound developmental delay, died at 3d due to heart defect;
  13-N-
qt32/
1-2
female/
1w
PBL de novo 48,XX,+marx2[15%]/
47,XX,+mar[75%]
46,XX[5%] at birth
At 7y 5/75/20
inv dup(13)(qterq32: :q32qter) wcp 13; cep13/21, 14/22, 15, 16, X; probe in 13q32-q33 and subtelomere probe 13q see below {7; 12; 16}
{8} case 13h
{44}
 
at birth right microphtalmia and coloboma, plus tumor of right optic nerve, malformed ears with preauricular ear pit, hemangiomas on forehead, scalp and neck, syndactyly 2./3. toes; At 7y moderate mental retardation, seizures, dysmorphic features, high arched palate, poorly implanted decayed teeth, obese, bulbous nose, bifid tip, epicanthus, early hypotonia, later ataxia and hemiparesis, PDA at birth but normal at 11y; 
  13-N-
qt32/
1-3
male/
1w
PBL/ fibroblasts de novo 47,XY,+mar[100%]
(sSMC in fibroblasts 100%)
inv dup(13)(qterq32: :q32qter) FISH as specified in {8} see below {8} case 13g {12}
{14; 16; 44}
 
at birth up to 5y normal weight; at 8y below normal weight; normocephaly, bifid nose anteverted nostrils, hypertelorism, iris and choroid coloboma, seizures, hypotonia, MRI at 10y shows swollen gray matter, hemangiomas of head and back; tapering fingers; died at 10y
  13-N-
qt32/
1-4
male/
6m
PBL de novo 48,XY,+marx2[26%]/
46,XY[74%] at age of 7y
at 6m the two sSMC in 3/25 cells
inv dup(13)(qterq32: :q32qter)x2 different FISH probes as specified in {4} see below {4} case 3; {12; 16; 25}  
at birth overlaying occiput which was asymmetrical; low-set ears; eyes widely spaced and cyst in right eye; from 6m on developmental delay; from 21m on seizure disorder; hypertelorism, ptosis of right eyelid, anteverted nares
  13-N-
qt32.3/
1-1
n.a./
newborn
PBL de novo 49,+marx3[23%]/
46[77%]
inv dup(13)(qterq32.3: :q32.3qter)x3 array-CGH, subtelomere FISH Died shortly after birth, very dysmorphic, low set and abnormal ears, preauricular pits {41}  
  13-N-
qt32.3/
2-1
female/
postnatal
AF n.a. 47,XX,del(13)(q32.3),
+mar[100]
inv dup(13)(qterq32.3::q32.3qter) M-FISH, CGH n.a. {0} case provided by Dr. C. Fuster (Spain)  
                     

 

 

other neocentromere 13 cases (no sSMC):

reference {4} 1 case {16}

reference {8} 2 cases {16}

reference {17} 1 case

reference {21} 1 case

reference {46} case 3

 

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  
  13-N-
IMB-
qter/
1-1 to
?-1
see {40} {40}