FISH

SMALL SUPERNUMERARY MARKER CHROMOSOMES

- sSMC 8 -

           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 8   maternal   paternal   unclear


PATIENTINFORMATION for sSMC(8)

the probably non-dosage sensitive pericentric region of chromosome 8


SCHEMATIC CYTOGENETIC DEPICTION                    
 sSMC-8 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]

 critical region 40.35 --- 42.50 uncritical region   [43.20 centromere 48.10]   uncritical region ?61.33 --- ?52.92 critical region

Below adapted for UCSC hg19, 2009

 critical region 40.15 ---  42.40 uncritical region   [43.10 centromere 48.10]   uncritical region ?61.15 --- ?52.74 critical region

 DISCLAIMER



 Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

8p - proximal 8q - proximal
symptoms
autism 24 % 0 %
brain malformations 6 % 0 %
developmental delay 88 %
71 %
dysmorphic face  41 %
86 %
finger or toe/foot malformations 12 % 29 %
hearing problems/ loss (sensor neural) 6 % 14 %
heart defect 6 % 14 %
hip problems 6 % 14 %
hypotonia 12 % 14 %
joint problems 12 % 0 %
macrocephaly 12 % 0 %
mental retardation   41 %
14 %
microcephaly 0 % 14 %
omphalocoele 0 % 14 %
overgrowth 18 % 0 %
seizures 6 % 0 %
urethral problems 0 % 14 %
number of cases (marked with “°” below) 17
7

 


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  
  08-O-
p23.1/
1-1
female/
30y
PBL n.a. 47,XX,+mar[27%]/
46,XX[73%]
see below different FISH-probes: telomeric probe; all wcp  in an array; GATA 4 in 8p23.1 no phenotypic signs - intelligence normal {9} case 3
{101}
 
r(8)(::p23.1q1?1::)/*r(8;8)(::p23.1q1?1::p23.1q1?1::), proportion unknown
  08-O-
p21.1/
1-1
female/
prenatal
AF n.a. 47,XX,+mar[10]/
46,XX[20] 
mar(8)(:p21.1q11.1:)
aCGH
: 29.48-43,95 MB
aCGH see below {100} case 10
 
advanced maternal age; no phenotypic signs at birth
  08-O-
p11.22~
11.21/
1-1
female/
prenatal
AF n.a. 47,XX,+mar[67%]/
46,XX[33%]
min(8)(:p11.22~11.21q11.1:)
FISH-d
ata: RP11-503E24 at 42.5MB on sSMC
 cenM;subcenM see below {0} provided by Dr. Hickmann, Düsseldorf, Germany  
Amniocentesis due to advanced maternal age;  no ultrasound abnormalities; normal child born, normal at 14 months
  08-O-
p11.21/
1-1
female/
prenatal
AF maternal 47,XX,+mar[43]/
46,XX[7]
r(8)(::p11.21q11.1::)
FISH-data: RP11-64C22 at 42.5MB on sSMC
M-FISH; cenM;subcenM;
telomere-probes
see below {1} case 14
{2} cases 2 
       and 12
{4} case 2
 
Amniocentesis due to advanced maternal age; no ultrasound abnormalities; mother without any clinical signs; normal child born
  08-O-
p11.21/
1-2
male/
prenatal
AF n.a. 47,XY,+mar[25]
46,XY,[2]
 r(8)(::p11.21q11.11::)
42.64-47.06MB
SKY, MLPA, array-CGH; UPD-test see below {89}  
Amniocentesis due to advanced maternal age;  normal child born, apart from multicystic kidney disease and mild ventriculomegaly
  08-O-
p11.21/
2-1
male/
30y
PBL n.a. 47,XY,+mar[44]/
46,XY[6]
min(8)(:p11.21q11.1:)
FISH-data: RP11-503E24 at 42.5MB on sSMC
aCGH: 39,019,000-43,330,000 MB
cenM; subcenM
aCGH
see below {0} provided by Jasen Anderson, Brisbane,  Australia  
normal male - with fertility problems
  ***
08-O-
p11.21/
3-1
***
female/
prenatal
AF n.a. 47,XX,9ph+,+mar[15]
46,XX,9ph+[10]
 r(8)(::p11.21q12.1::)
FISH-data: RP11-503E24 at 42.5MB and RP13-116A4 at 48.3MB and RP11-114M5 at 59.62 on sSMC
aCGH: 48.068,000-61.329,000 Mb; confirmed by FISH using BACs
cenM; subcenM
aCGH
see below {0} case provided by Dr. Schliephacke, Linden, Germany  
Amniocentesis due to  advanced maternal age;  normal child born; normal at 14m of age
  08-O-
p11/
1-1
female/
prenatal
AF de novo 47,XX,+mar[16]/
46,XX[7]
min(8)(:p11q11:)  M-FISH; cenM; UPD-test see below {2} case 3 
{4} case 3
 
Amniocentesis due to advanced maternal age; no ultrasound abnormalities; no clinical symptoms 2 years after birth
  08-O-
p11/
1-2
female/
prenatal
AF
(EKF-
cellbank)
de novo 47,XX,+mar[33]/
46,XX[2]
min(8)(:p11q11:) 
interphase cytogenetics with centromeric probe 8 in uncultured amniocytes: cep8x3[64]/cep8x2[62]
 cenM; UPD-test see below {50} case 8-13  
Amniocentesis due to advanced maternal age; no ultrasound abnormalities; normal child born in gest. week 41; weight: 3160g; length: 51cm; head circumference: 32cm; APGAR score: 9; 9; 10 
  08-O-
p11.1/
1-1
male/
44y
PBL n.a. 47,XY,+mar[7]/
46,XY[10]
min(8)(:p11.1q11.21:)[9]/
min(8)(:p11.21
q11.1:)[5]
FISH-data:  RP13-116A4 at 48.3MB on sSMC
 cenM, subcenM normal male, sSMC detected due to ICSI in partnership {74} case 12  
  08-O-
p11.1/
2-1
see McCl-08-O-p11.1/2-1   {82; 91}  
  08-O-
p11/
1-1
female/
prenatal
AF/PBL de novo 47,XX,+mar[50]/46,XX[10] interphase 83% min(8)(::p11q11.2::) 
FISH-data:  RP13-116A4 at 48.3MB on sSMC
aCGH: 8p11.2-8p11 (43,192,308-48,198,00 MB)
cenM; subcenM prenatally detected - child born, normal at a few months {0} provided by Jasen Anderson, Brisbane,  Australia  
  08-O-
p10/
1-1
male/
27y
PBL de novo 47,XY,+mar[10]/
46,XY[12]
?r(8)(::p10q12::)   CGH; wcp 8, cep 8 recurrent abortions in his wife {51} case 6
{74} case 13
 
                     

 

O-cases with unclear/insufficient characterization of the sSMC itself (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  
  08-
CO-1
female/
1m
PBL de novo 47,XX,+mar[~55%]/ 46,XX[~45%] mar(8)* all available centromeric probes normal at age of 7y {15} case 38587  
  08-
CO-2
male/
prenatal
PBL de novo 47,XY,+mar[~50%]/ 46,XY[~50%] r(8)(::p1?1.2q1?1.2::)* M-FISH see below {43}   

amniocentesis due to echogenic bowels and increased values for TT; born in week 40 without complications; normal at age of 5m

  08-
CO-3
female/
postnatal
PBL n.a. 47,XX,+mar[?%]/
46,XX[?%]
mar(8) centromeric probes, wcp8, tel 8p miscarriages {63} case 8 
{74} case 14
 
  08-
CO-4
female/
prenatal
PBL de novo 48,XX,+marx2[4]/
47,XX,+mar[17]/
46,XX[4]
?r(8)(::p11q11::)* centromeric probes advanced maternal age + anxiety; normal girl born and still normal at 6y {48} case 3   
                     

 


References

Cases with iso-chromosome 8p (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  
  08-W-
iso
/

1-1
female/
6y
PBL
cell line at ECACC DD0824
de novo 47,XX,+i(8p)[31]/
46,XX[69]
n.a. n.a., UPD-rest see below {5} case 6
{6}
 

mental retardation, hypotonia; wide mouth; slender fingers, height and weight <3rd centile

  08-W-
iso
/

1-2
male/
prenatal
AF; CH; PBL de novo CH: 47,XY,+(mar)[60%]/
46,XY[40%]
in AF no mar detected; in PBL mar in 5%
i(8p) wcp8, subtel 8p .

 

{54}  

normal in ultrasound, cytogenetics due to advanced maternal age; normal at birth; at age of 2m slow growth, feeding difficulties; delayed psychomotor development hypotonia, poor visual contact; at 4m epileptic seizures with secondary generalization; at 5m those seizures evolved into spasms, at 11m severe developmental delay, microcephaly, diffuse hypotonia, hypoplastic corpus callosum, after Vigatrin treatment child got better

  08-W-
iso
/

1-3 to
1-13
male or female/
postnatal
 PBL de novo 47,+i(8p)[diff. mosaic grades] n.a. n.a. clinical abnormal {55 - review of several reports} see also {78}  
  08-W-
iso
/

1-14
n.a. /
prenatal
AF de novo mos 47,XN,+mar[?%]/'
46,XN[?%]
i(8p) FISH agenesis of corpus callosum, IUGR, TOP {89}  
  08-W-
iso
/

1-15
female/
perinatal
PBL; AF de novo 47,XX,+i(8p)[10]
(in AF in week 16: 12 of 12 cells normal!)
i(8p) wcp8, subtel 8p, UPD-rest clinical abnormal as described in {57}, ultrasound abnormalities, child died at27 day of life, {57}  
  08-W-
iso
/

1-16 to
1-17
male /
postnatal
 PBL de novo 47,XY,+i(8p)[diff. mosaic grades] n.a. n.a. clinical abnormal - see {58} {58}  
  08-W-
iso
/

1-18
male /
postnatal?
 PBL? de novo 47,XY,+mar[18%]/
46,XY[82%]
i(8p) array-CGH n.a. {85} case 26912  
  08-W-
iso
/

1-19
male /
3y?
 PBL de novo 47,XY,+mar[78%]/
46,XY[22%]
i(8p) FISH subtle facial abnormalities; agenesis of corpus callosum {86}  
  08-W-
iso
/

1-20
male/
prenatal
AF/ fetal PBL de novo AF: 46,XY
47,XY,+mar[30%]/
46,XY[70%]
i(8p) array-CGH; FISH agenesis of corpus callosum, bilatheral colpocephaly, IUGR, TOP {88}  
                     


 


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  
  08-W-
p23.3/
1-1
male/
postnatal
PBL n.a.  47,XY+mar[100%] min(8)(:p23.3p23.3:
:p23.1
p23.1:
:p12.11
q10:)*
array-CGH see below {81} case 2   
family history of Rieger syndrome, developmental delay , epilepsy at age 18
  08-W-
p23.1/
1-1  °
male/
3y
PBL
skin fibroblasts
de novo blood: 47,XY,+r[29]/
46,XY[21]
fibro: 47,XY,+r[15]/
46,XY[68]
r(8)(::p23.1q10::)* all centromeric probes; subtelomere probes 8p, 8q
YACs {42}; UPD-test
see below {42; 44}  
Born at term without complications; at birth, poor sucking at breast and evidence of frontopalpebral and sacral hemangiomas; main motor milestones achieved within the lower range of normality; expressive language abilities developed slowly; atypical behavior with several autistic features such as stereotyped conduct, avoiding gaze and echolalia language. At 3 y: OFC 51 cm (75th centile), weight 14 kg (50th centile), and height 105 cm (>90th centile). Minor facial anomalies: elongated face with high prominent forehead, bitemporal narrowing, high-arched eyebrows with lateral thinning, slightly down-slanting deep set eyes, flat nasal bridge with broad nasal tip, large mouth with thick lips and everted lower lip, high-arched and narrow palate, deep palmar creases; slender trunk with widely spaced nipples; significant hyper mobility of the shoulders and hyper flexibility of the finger joints .
  08-W-
p22.1/
1-1
male/
prenatal
AF/PBL de novo 47,XY,+mar[3]/
46,XY[37]
r(8)(:p22.1q12.1:)
aCGH
-data: 18.10-61.10 Mb
M-FISH,
aCGH,
UPD-test
see below  {99}  
amniocentesis due to fetal pyelectasis in 2. trimester; normal child born appart from mild bilatheral hydronephrosis
  08-W-
p21.2/
1-1  °
male/
7y
PBL de novo 47,XY,+mar[30%]/
46,XY[70%]
interphase FISH 50%, each
min(8)(:p21.2q11.1:)
FISH-data: RP11-503E24 at 42.5MB
on sSMC
M-FISH, subcenM;
MCB
see below  {0}  provided by Dr. Anikó  Ujfalusi, Hungary  
Birth weight: 2680 g (40. gestation week), second pregnancy, first pregnancy ended by spontaneous abortion; familiar, prenatal and perinatal anamnesis negative. Clinical data: attention deficit, slight mental retardation (IQ: 69), long philtrum, clinodactyly of fifth finger, corpus callosum dysgenesis (MRI).
  08-W-
p21/
1-1
female/
5y
PBL de novo 47,XX,+mar[50%]/
46,XX[50%]
FISH:
min(8)(:p21
q11.21:)[4]/
r(8)(::p21
q11.21::)[8]/
r(8)(::p21
q11.21:
:p21
q11.21::)[3]/
min(8)(:p21
.21:),
min(8)(p21
q10:
:q10
p21)[1]
array-result: breaks in 8p21.3 (23.11MB )
and 8q12.1 (59.62MB) acc. to {62}
26.21-47.90 MB according to {0}
midi, subcenM-FISH,
all human telomeres; array-CGH
see below  {0}
{50} case 8-1; {62} case D
 
agenesis corpus callosi, deep set , malrotated ears, facial dysmorphism, psychomotor and developmental retardation
  08-W-
p12/
1-2   °
female/
prenatal
AF/ PBL de novo 47,XX,+r[8%]/
46,XX[24%]
postnatal ring  in 10/20 cells
r(8)(?::p12q11.1:
:q11.1
p12::)*
all available centromeric probes; wcp 8 ; pcp 8p ; pcp 8q see below  {29} case 3  
Hydrocephalus notes in ultrasound; birth at 37weeks of gestation; weight, length and OFC at 75. centile, several large hemangiomas at neck and back; forehead sloped and was asymmetric; supraorbital ridges hypoplastic; inner canthal distance at 95. centile; broad nasal root, midface prominent; short neck with excess of nuchal skin; hip rotation; tow nails hypoplastic; nipples placed asymmetrically
  08-W-
p12/
2-1
female/
16y
PBL de novo 47,XX,+r[14]/
46,XX[6]
postnatal ring  in 10/20 cells
r(8)(::p12q12::) all available  wcp; midi see below  {32}   
Primary amenorrhea at 16y; blind ending vagina; multicystic and enlarged ovaries; normal hormone status; mild mental retardation; facial asymmetry; long & low set ears; hypertelorism, upslanting palpebral fissures; unilateral ptosis; unilateral epicanthal fold, strabismus, bushy eyebrows, prominent nasal tip, long philtrum, prominent lower lip; high arched palate, scoliosis, bilateral hip dysplasia, longitudinal plantar creases; sacral hypoplasia, absent os coccyx; left side renal hypoplasia; enlarged right kidney; length >40. centile, weight >75. centile; glaucoma at age of 4 m; no developmental retardation.
  08-W-
p12/
3-1  °
male/
prenatal
AF de novo 47,XY,+mar[16]/
46,XY[4]
?min(8)(:p12q10:)* CGH, cep 8 see below {51} case 3  
Marker prenatally detected due to increased fetal nuchal translucency; at birth normal in growth parameters, but loose skin at the back of the neck and large ears. At 1y facial dysmorphism (antimongoloid palpebral fissures, maxillary hypoplasia, long philtrum, prominent lower lip, large dysplastic ears1), hyperextensibility of fingers, large toes. At 3 y loose skin at back of neck had decreased but slender trunk present plus hyperactivity and speech delay
  08-W-
p12/
3-2   °
male/
2y
PBL n.a. 47,XY,+mar[100%] min(8)(:p12q11.1:)
32,339,966-43,874,681 MB
aCGH, subcenM see below {0}provided by A. Patino Garcia, Papmplon, Spain  
Mild mental retardation, labile attention, tachyphemic speech and dyslalia, developmental delay
  08-W-
p12/
4-1
n.a./
postnatal
PBL n.a.  47,+mar[51%]/
46[49%]
min(8)(:p12q11.23:)*
distal clone in 8p RP11-350N15 (38.29 MB)
distal clone in 8q RP11-373H15 (53.54MB)
array-CGH see below {64} case 5   
developmental delay, dysmorphic features
  08-W-
p12/
5-1
female/
prenatal
AF de novo 48,XX,+mar1,+mar2[5]/
47,XX,+mar1[5]/
47,XX,+mar2[4]/
46,XX[1]
mar1:
min(8)(:q11.1
q11.23:)
43.20-50.67 MB
mar2:
min(8)(:p12
q11.23:)
38.29-50.67 MB
array-CGH
cep 8
BAC-FISH
VSD in sonography, micrognathia, TOP {84}  
  08-W-
p11.2/
1-1
female/
15m
PBL de novo 47,XX,+r[100%] r(8)(::p11?.2q11?.2::)*
plus not nearer specified number of double rings
all available centromeric probes  see below {16}  
Born at term; birth weight: 3500g, APGAR score 5/9; temporally intubations was necessary in the first 48h; developmental delay at age 6m; seizures from 13m; at 15m: head circumference 44cm (<5%), weight 8.7kg (75%), height 73cm (25%), diminished generalized muscle tonus; minor facial anomalies like small epicanthal fold, round face, flat nasal bridge
  08-W-
p11.2/
1-2
male/
16y
PBL n.a. 47,XY,+mar[100%] r(8)(::p11.2q12::)[12]/
r(8;8)(::p11.2
q12:
:p11.2
q12::)[1]
FISH-data: 32.9-48.3 MB
aCGH: 37.77-49.05 and 60.56-75.41
CGH, Array CGH, subcenM, BACs; arrayCGH  see below {0} provided by Dr. C. Fuster, Spain  
Mental retardation, accused myopia, deafness and flat feet, elongated face, bad implantation of teeth, big ears, deformity of chest and back, no kneecaps and a limited elongation of arms and legs, long neck and very long fingers, always contracted in flexion.
  08-W-
p11.2/
1-3
male/
2y
PBL n.a. 47,XY,+mar[7]/
46,XY[23]
r(8)(::p11.2q12::) cenM subcenM  see below {0} provided by Dr. M. Ergun, Turkey  
Craniosynostosis, Rhetinitis pigmetosa, nystagmus, downslanting palpebral fissures, pulmonar stenosis, brachidactyly, dysplastic ears, cubid bow shaped mouth, anteverted nares, rethrognathy, hypospadias, urinary reflux, supernumerary nipples
  08-W-
p11.2/
2-1
male/
8y
 PBL n.a. 47,XY,+mar[14]/ 46,XY[3] min(8)(:p11.2q11.2:)[4]/
r(8)(::p11.2
q11.2::)[2]/
min(8)(:p11.2~p11.1:
:q11.2
p11.2:)[1]
cenM; subcenM autism, mental retardation {0} provided by Dr. T. Martin, Homburg, Germany  
  08-W-
p11.2/
3-1
male/
29y
 PBL n.a. 47,XY,+mar[100%] r(8)(::p11.2q13~21.1::) M-FISH; subcenM abnormal phenotype {0} provided by Dr. M. Mulhatino Rio de Janeiro, Brazil  
  08-W-
p11.23/
1-1
n.a./
postnatal
 PBL de novo 48,+marx2[45%]/
47,+mar[45%]/
46[10%]
r(8)(::p11.23q11.21::8p22::)*
size in p 4.5MB, in q 2.2 MB plus 8p22 material
n.a.;  subcenM with 3 BACs, array CGH Learning disabilities; obesity; dysmorphic features {70} case 12  
  08-W-
p11.23/
2-1  °
male/
6m
 PBL de novo 47,XY,+mar[17]/
46,XY[13]
min(8)(:p11.23q11.21:)
aCGH: 38.96-50.11 MB
array CGH severe hypotonia; hypospadias {90} case P-4  
  08-W-
p11.23/
2-2
female/
1y
 bone marrow / bucchal mucosa de novo in bucchal mucosa: 47,XX,+mar[38%]/
46,XX[62%]
min(8)(:p11.23q11.21:)
array-data: 36.67-50.14 MB (? hg19)
array CGH frontal bossing, downslanting palpebral fissures, hypertelorism, low nasal bridge; JMML {94; 95} case D703  
  08-W-
p11.23/
3-1  °
male/
6y
 PBL de novo 47,XY,+mar[20]/
46,XY[7]
min(8)(:p11.23q11.1:)
breakpoinaCGH: 38.94-47.85 MB
different FISH-probes; array CGH global developmental delay, autism, and low muscle tone {92} case 7  
  08-W-
p11.22/
1-1
female/
3y
CH
AF
PBL
de novo CH: 47,XX,+r[16]/
46,XX[14]
AF: 35/4
PBL: 96%/4%
r(8)(:p11.22q11.22:)*
breakpoint in 8p: 3.3 or 3.1 Mb from cep
breakpoint in 8q: 1.85Mb or 0.8 from cep
all wcp probes; array-CGH; UPD-test see below  {69}
{70} case 11
 
Ref 69: Birth at 34 weeks of gestation by cesarean after an uncomplicated pregnancy; weight 2.270 kg, length 45 cm, head circumference 32 cm. Apgar 9 at 10 min, 10 at 50 min). At 11 m, head circumference 44.5 cm (95th centile), weight 7.94 kg (10-25th centile), length 70 cm (25th centile); flat occiput and a right supernumerary nipple. The baby could babble. Early development normal, including head control at about 4 months and sitting at 8 months. She achieved independent walking at 20 months. Language development presented normal early language milestones; pointing was present late, at 18 months. She learned a few words around 2 years and was able to make poor sentences. At the age of 3 years, the Griffiths Scale of developmental assessment gave an age-equivalent score of 23 months, with lower scores in language, performance and social skills, and a General Quotient of 66. Behavioral observation showed a hyperactive profile, with attention deficit and poor concentration abilities.
Ref 70: Developmental delay; head control obtained at 4 months of age; sitting unsupported at 8 months of age; walked at 20 months of age; pointed at 18 months of age; had “a few words” at 2 years of age; at 3 years of age, the patient had a developmental assessment providing an age-equivalent score of 23 months; hyperactivity with attention deficit; supernumerary nipple; normal growth parameters; normal echocardiogram; normal abdominal ultrasound; normal ophthalmology exam
  08-W-
p11.22/
2-1
male/
postnatal?
 PBL? n.a. 47,XY,+mar[57%]/
46,XY[43%]
mar(8)(:p11.22q11.1:) array-CGH abnormal {85} case 26750  
  08-W-
p11.21~
11.22/
1-1  °
male/
15y
PBL
(EKF-
cellbank)
de novo 47,XY,+mar[100%] r(8)(::p11.21~11.22q11.1::)
FISH-data:
42.5-49.5 MB
cep probes; BACs, subcenM; UPD-test see below  {97} case 9
 
 
Atypical autism diagnosed at age 5. Physically normal to somewhat late on most milestones. Walking with 20 months. He lost some cognitive skills around 2 years old. Before that he was more connected and interacted more with environment. He had some language but not appropriate for age -- and he stagnated cognitively between 2-5 with little language acquisition. He responded extremely well to his ABA program started at 5 and was able to attend regular school at age 7 with an aide. His IQ scores vary widely. HAWIK III at 8.2y - 71 K-ABC Intellectual possibilities at age 12.5 y K-ABC: result - 96; Vineland Adaptive Behavior Scales at 7 y 62. At 15 y physically normal -- full puberty
  08-W-
p11.21/
1-1  °
male/
5y
PBL de novo 47,XY,+mar[36]/
46,XY[14]
min(8)(:p11.21q11.1:)* all available centromeric probes; wcp 8; pcp 8p ; pcp 8q see below  {29} case 1  
Normal pregnancy and birth; 4400g at birth; obstructive sleep apnea; at 5y attention deficit disorder, seizures, developmental delay; OFC at 80. centile; forehead cowlick, upswept frontal hairline; nasal tip up-turned and slightly broad; thin upper lip; hyper mobility of small joints
  08-W-
p11.21/
1-2  °
female/
11y
PBL de novo 47,XX,+mar[50] min(8)(:p11.21~11.22q11.1:)* all available centromeric probes; wcp 8; pcp 8p ; pcp 8q  see below  {29} case 2  
at birth anomalous pulmonary venus return noted; at 5y development of idiopathic thrombocytopenia; precocious puberty at 7y; obesity at 11y; bilateral epicanthal folds, eyes slightly deep set
  08-W-
p11.21/
1-3  °
female/
postnatal
 PBL
cell line at ECACC BO1091
n.a. 47,XX,+mar[60%]/
46,XX[40%]
min(8)(:p11.21→q11.1:)
FISH-data: RP11-503E24 at 42.5MB
on sSMC
cenM, subcenM global developmental delay {60} case 10  
  08-W-
p11.21/
1-4  °
n.a./
postnatal
PBL n.a. 47,+mar[100%] min(8)(:p11.21~11.22q10:)*
distal clone in 8p RP11-350N15 (38.3MB)
cep 8
array-CGH
see below {64} case 3   
developmental delay
  08-W-
p11.21/
1-5  °
female/
3y
 PBL n.a. 47,XX,+mar[100%] min(8)(:p11.21q11.1:)
FISH-data: RP11-503E24 at 42.5MB
on sSMC
cenM, subcenM; UPD-test at 3 years developmentally retarded, mentally retarded, psychomotor deficiencies. {0} provided by Dr. Kunze, Gelsenkirchen, Germany  
  08-W-
p11.21/
1-6  °
male/
11y
 PBL n.a. 47,XY,+mar[10]/
46,XY[10]
min(8)(:p11.21q11.1:)
FISH-data: RP11-503E24 at 42.5MB
on sSMC
cenM, subcenM severe developmental delay. {0} provided by Dr. Prager, Dresden, Germany  
  08-W-
p11.21/
2-1
male/
7m
PBL; skin fibroblasts de novo 47,XY,+mar[28]/
46,XY[22]
(skin fibroblasts without mar in 25 metaphases) 
min(8)(:p11.21q11.21:)* cep 8 see below  {21}  
Born after uncomplicated pregnancy; weight 3579g (75th centile) after cesarean section due to breech position; APGAR 8/?/9; right kidney moderately hyponephrotic, anus anteriorly placed, contractures of the fingers, overlap of toes, hypoplastic or absent patellae. At age of 7m skeletal anomalies, developmental delay, simple ears, camptodactyly of 3. finger, HC and height at 90th centile; eversion of lower lip, deep plantar creases, ulnar deviation of fingers 3-5 bilaterally, malalignement of right foot; extra vertebrae, advanced bone age. At 2.5y normal motor development and normal receptive language skills but significant delay in expressive language. At 3y growth delay; 
  08-W-
p11.21/
2-2
male/
postnatal
 PBL
cell line at ECACC CC0010
n.a. 47,XY,+mar[40%]/
46,XY[60%]
min(8)(:p11.21q11.21:)
FISH-data: RP11-503E24 at 42.5MB an
d RP13-116A4 at 48.3MB on sSMC
cenM, subcenM developmental delay {60} case 11  
  08-W-
p11.21/
2-3
female/
1y
Bone marrow, skin fibroblasts de novo skin interphase:
47,XX,+mar[34%]/
46,XX[64%]
in bone marow: sSMC in 80%
min(8)(:p11.21q11.21:)
array-data: 40.08-49.62 MB (? hg19)
array-CGH, Interphase-FISH mild psychomotor delay; detected due to JMML {94} case D600  
  08-W-
p11.21/
3-1  °
male/
43y
PBL de novo 47,XY,+mar[15]/
46,XY[10]

dic(8;8)(::p11.21q11.1: :p11.21q11.1::)
FISH-data: RP11-64C22 at 42.5MB on sSMC
aCGH: 8p21.1q11.1: 28,656,212-47,062,622 Mb

cenM;
subcenM;
aCGH
see below  {50} case 8-7  
Born at term after a normal pregnancy, with birth weight 3000g, length 50cm. There was developmental delay. He has a severe mental retardation, and his behavior is autistic. At the age of 37 years, the phenotype is normal, not dysmorphic. He has a normal biometry. Neurological examination is normal. Fragile X screening : no expansion in the FMR1 region
  08-W-
p11.21/
3-2   ° 
male/
18y
PBL n.a. 47,XY,+mar[15]/
46,XY[25]
min(8)(:p11.21q11.1:
:q11.1
p11.21:)
 cenM;
subcenM
see below  {0} provided by Dr. Iourov, Moscow, Russia  
Moderate mental retardation, overgrowth syndrome, dolichomorphic type, scoliosis, long face, low-set dysplastic ears, deafness, palmar crease, umbilical hernia, partial depigmentation of hair, dyslalia, autistic features
  ***
08-W-
p11.21/
4-1  °
***
n.a./
postnatal
PBL n.a. 47,+mar[47%]/
46[53%]
r(8)(::q10p11.2:
:p11.1
q10::)*
distal clones in 8p RP11-301G7 (40.35 MB) and RP11-44K16 (chr. 14!?)
array-CGH see below {64} case 4   
developmental delay
  08-W-
p11/
1-1
male/
3y
PBL de novo 47,XY,+r[27%]/
46,XY[73%]
r(8)(::p11q11::)* midi; UPD-test see below {7} case K  
mental retardation and behavioral problems at age of 2y. At 8y mild mental retardation, proportionate general build, no major malformations, mild lydysmorphic deep-set eyes & widely spaced teeth
  08-W-
p11/
1-2
male/
29y
PBL n.a. 47,XY,+r[19]/
46,XY[6]
r(8)(::p11q11::) M-FISH; cep8; YAC 959A4 see below {39} case 1  
mild intellectual delay but no dysmorphic features
  08-W-
p11/
2-1  °
male/
3.5y
PBL de novo 47,XY,+r[100%?] r(8)(::p11q11.2?2::) CGH, cep8, wcp8 see below {49}   
developmental delay, normal birth with birth weight 6lb 10oz; at 3.5y: weight 25. centile, height 75. centile, OFC <5. centile. microcephaly with narrow forehead, mild epicanthal folds, hypoplastic alae nari, bulbous tip and soft ears mildly decreased muscular tone.
  08-W-
p11.1/
1-1
male/
3m
PBL de novo 47,XY,+mar[2]/
46,XY[28]
min(8)(:p11.1q11.21:)[11]/
r(8)(::p11.1
q11.21::)[2]/
r(8)(::p11.1
q11.21:
:p11.1
q11.21:)[1]/
r(8)(::p11.1
q11.21:
:p11.1
q11.21: 
 :p11.1q11.21:)[2]/
dic(8)(:q11.21
p11.1:
:p11.1
q11.21:)[5]/
dic(8)(:q11.21
p11.1:
:p11.1
q11.1:)[2]
FISH-data: RP11-64C22 at 42.5MB and RP11-11C20 at 52.8MB on sSMC
aCGH: 8q11-8q11.23 (47,631,690-53,095,051 Mb)

M-FISH;
subcenM; 
MCB;
aCGH

see below {50} case 8-9   
born in week 34 of gestation; eutroph at birth; micro anomalies; sSMC detected already in amniocytes - amniocentesis due to advanced maternal age; more SMC in placenta and umbilical chord tissue than in umbilical chord blood
  08-W-
p11.1/
2-1  °
male/
3y
PBL
(EKF-
cellbank)
de novo 47,XY,+mar[70%]/
46,XY[30%]
min(8)(:p11.1q11.23:)
FISH-data: RP13-116A4 at 48.3MB on sSMC
Array: 43.19-54.86 MB
cenM, subcenM, midi;
array-CGH; UPD-test
see below {0} provided by Dr. C. Yardin,
Limonge, France
 
developmental delay and facial dysmorphism
  ***
08-W-
p11.1/
3-1  °
***
male/
prenatal
AF n.a. 47,XY,+mar[20%]/
46,XY[80%]
r(8)(::p10~11.1q11.21::)
FISH-data:
RP13-116A4 at 48.3MB on sSMC
Array: 43.79-52.92 MB
cenM, subcenM advanced maternal age, omphalocoele, TOP {0} provided by Dr. M. Stumm,
Berlin, Germany
 
  ***
08-W-
p11.1/
4-1  °
***
male/
newborn
PBL n.a. 47,XY,+mar1[?%]/
47,XY,+mar2[?%]
r(8)(::p10~11.1q11.21::)*

Array: 43.79-48.24 MB and       43.79-48.59 MB
array-CGH prominent forehead, plagiocephaly, hypertelorism, low set ears {83} case 2  
  08-W-
p11.1/
5-1  °
male/
4y
PBL n.a. 47,XY,+mar[5]/
46,XY[15]
min(8)(:p11.1q21.?3:) M-FISH,
subcenM,
see below {0} provided by Dr. Iourov, Moscow, Russia  
developmental delay, hip dysplasia, cardiomyopathy, partial right ptosis, congenital stridor, short neck, epicantic folds, low-set dysplastic ears, frontal bossing, broad/flat nasal bridge
  08-W-
p10/
1-1  °
male/
1.5y
PBL
(EKF-
cellbank)
de novo 47,XY,+r[15] r(8)(::p10q23.3::) cenM; 
MCB
see below {0} provided by Dr. B. Albrecht,
Essen, Germany
 
psychomotor retardation; hydronephrosis, megaureter, craniofacial dysmorphism, hypertelorism, ear- abnormalities, finger and foot dysmorphism, develops café-au-lait spots no urethra, clubfoot, shortened siews in fingers and toes, myopia, slight hardness of hearing
  08-W-
p10/
2-1  °
female/
1y(?)
PBL
Fibroblasts
de novo blood: 47,XX,+r[40%]/
46,XX[60%]
fibro: 47,XX,+r[72%]/
46,XX[28%]
r(8)(::p10q21.1::) midi; UPD-test see below {7} case J
{8} case C
{25} case 3
 
Born at term; birth weight: 3315g; length: 47cm. She could sit without support at 12±13 months, & walk without support at 3y of age. Some of the delay explained by pes equinovarus and repeated operations on her feet. No delay in fine motor skills. Hearing loss and intelligence had been estimated as 1y below normal. She had an accessory nipple and narrow shoulders, coarse face, hypertelorism, bulbous nose, low-set ears.
                     

 

 

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  
  08-W-
IMB-q12/
1-1
female/
8y
PBL n.a. 46,XX,dup(8)(q12) not specified see below {79}  

severe mental retardation, narrow forehead, prominent metopic suture, postaxial polydactyly of fingers, sacral sinus, hypotonia; At 1 and 4 y left and right Wilmstumor

  08-W-
IMB-q12/
2-1  °
male/
6y
PBL n.a. 46,XY,dic(8)(pterq11::p11.2?3qter)[16]/45,XY,-8[4] subcenM see below {96}  

microcephaly, autism, developmental delay, dysmorphic face, joint problems, mental retardation, chest deformation

                   

 

W-cases with unclear/insufficient characterization of the sSMC itself (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  
  08-
CW-
1
female (2x)
male(1x)/
at birth, 4y, 30y
PBL paternal 47,XX,+mar[97-98%]/
46,XX[3-2%] 47,XY+mar[10]/
46,XY[90]
min(8) .ish(wcp+) wcp 8 see below {18; 19}  

Father without any clinical signs; the frequency of the marker was 27% at age of 30y and 10% at age of 45y.
Both daughters had developmental delay, first daughter additionally with autistic behavior and preaxial polydactyly; Second daughter at birth with cardiac problems.

  08-
CW-
2
male/
41y
PBL n.a. 47,XY,+r[27] min(8) M-FISH; centromeric probe 8 analysis with the suspicion of fragile X-syndrome; no clinical details available {20} case 5  
  08-
CW-
3
male/
9y
PBL de novo 47,XY,+mar[75]/
46,XY[25]
min(8)(D8Z1+) midi; cep8 (D8Z1)

see below

{33}  

growth retardation at 9y; normal psychomotor development; idiopathic non familiar short stature

  08-
CW-
4
male/
10y
PBL de novo 47,XY,+mar[100%] min(8) .ish (cep8+) several cep probes see below  {34-35 case 2}   

monorchidism, cryptorchidism, mental retardation

  08-
CW-
5
male/
n.a.
n.a. n.a. 47,XY,+mar[100%] min(8) SKY dysmorphic features; developmental delay {12} case MP2  
  08-
CW-
6
female/
9y
PBL n.a. 47,XX,+mar[54%]/
46,XX[46%]
r(8)[49%]/
r(8;8)[6%]
 telomeric probe; all wcp  in an array;  developmental delay, severe intellectual delay, mild ataxia, dysmorphic facies {9} case 6  
  08-
CW-
7
male/
9y
PBL de novo 47,XY,+mar[50%]/
46,XY[50%]
r(8) all centromeric  probes see below {10} case 7  

globally delayed at age of 7y, broad nasal bridge, triangular face, large, posteriorly rotated low-set ears, divergent squint, clawing of tows2-5, hyper extensible elbows

  08-
CW-
8
female/
7.5m
PBL de novo 47,XX,+r[50] r(8)(wcp8+;D8Z2+) different FISH-probes: wcp8; cep8

see below

{13} case 1  

Born after an uneventful pregnancy; ultrasound at 5 months of gestation was normal; born by vaginal delivery and noted to have jaundice in the first week of life, which was thought to be due to breastfeeding. At 7.5m hypotonic, able to roll over but poor head control, could not sit without support. Her length, weight, and head circumference were all at the 25th centile for age; mild frontal prominence; ears low set with over folding at the superior helical regions; nose short and upturned. At age 2 y length at the 5th , weight slightly below the 5th , OFC at the 10th centile; speaking and putting words together; no health problems.

  08-
CW-
9
male/
6m
PBL de novo 47,XY,+r1[26]/
47,XY,+r2[24]
r(8)(D8Z2+)
r(8)(D8Z2++)
different FISH-probes: cep8

see below

{13} case 2  

Born by caesarian section after an uneventful term pregnancy. At age 6 m developmental delay and unusual appearance. Height, weight, and OFC were above the 95th centile for age; plagiocephaly with a prominence of left occiput and right forehead, epicanthic folds, highly arched palate, small nose and lingual frenulum tethering the tip of the tongue; right ear cup shaped, the left helix over folded; hypotonic. CT showed agenesis of corpus callosum. At age 22 m, patient's growth was normal for age. walking at age 26 m.

  08-
CW-
10
male/
prenatal
AF/ PBL de novo 47,XY,+r[31%]/
46,XY[69%]
postnatal ring  in 83%, at 5y in 95% of PBL
r(8) all available centromeric probes see below  {22; 23} case 24  

Amniocentesis due to advanced maternal age; in a twin pregnancy; Twin's chromosomes normal; At birth patients weight and OFC at the 80th percentile, length at the 75% percentile; mildly dysmorphic features including 2 posterior hair whorls, abnormal palmar crease, slight epicanthal folds, mildly hypoplastic and widely spaced nipples; poor receptive language skills, autistic behavior, moderate mental retardation, severe speech delay, difficulty with fine and gross motor coordination.

  08-
CW-
11
male/
prenatal
AF/PBL de novo 47,XY,+r[14]/
46,XY[12]
r(8)(D8Z1+) all cep in an array

see below

{24} case 1  

Amniocentesis after detection of right-sided chylothorax and ascites in ultrasound, child born at term with overlapping toes and talipes; at 3m developmental delay, poor head control, abnormal hand posture, abnormal feeding technique. No reaccumulation of the pleural effusion.

  08-
CW-
12
female/
21y
PBL n.a. 47,XX,+mar[34%]/
46,XX[66%]
r(8) .ish cep8+; GATA4(8p23.1)+, telomere+  telomeric probe; all wcp  in an array; GATA 4 infertility problem, mentally retarded (IQ 80-85; central obesity, short stature {9} case 2  
  08-
CW-
13
female/
3d
PBL
fibroblasts
de novo 47,XX,+r[9]/
46,XX[13]
ring in 9/20 cells in fibroblasts
2/9 where double rings
r(8) different cep probes including cep8

see below

{17}  

At age of 3 days poor suck and minor anomalies; born after a pregnancy complicated by preterm labor at 32 weeks of gestation; prenatal ultrasound study showed possible polyhydramnion. Delivery vaginally at 41 weeks of gestation with 3,799 g (90th centile); length 54 cm (95th centile), head circumference 34.5 cm (60th centile); multiple congenital anomalies like a small anterior fontanel, high sloping forehead, epicanthal folds, small palpebral fissures,  posterior hairline with excess nuchal skin, absent clitoris, and bilateral fifth finger, clinodactyly. 

  08-
CW-
14
male/
12y
PBL n.a. 47,XY,+r[?]/
46,XY[?]
r(8)  n.a. see below {40}   

low birth weight, mental retardation, microcephaly, short stature, hypotonia, minor facial anomalies: hypotelorism, bilateral epicanthic folds, long philtrum, thin lips, narrow palate, micrognathia and low-set ears. Digital anomalies: bilateral brachyclinodactyly of the fifth finger, cutaneous syndactyly between second and third fingers. 

  08-
CW-
15
male/
prenatal
AF de novo 47,XY,+mar[6]/
46,XY[38]
r(8)  n.a. Ultrasound abnormalities, double-outlet right ventricle, VSD, coarctation of aorta; child born {41} case 13  
  08-
CW-
16
male/
15y
AF de novo 47,XY,+mar[29]/
46,XY[33]
r(8)  wcp 8, cep 8 see below {53}   

neuromotor growth retardation, facial dysmorphism, height 157cm (10th centile), weight 37,5kg (<3rd centile), OFC 55cm (75th centile), pterygium colli, poor speech and language development, IQ 67

  08-
CW-
17
n.a./
prenatal
AF de novo 47,+mar[12]/
46[60]
r(8)  cep probes, wcp 8 Amniocentesis due to advanced maternal age, abnormal triple test and ICSI. TOP, congenital heart abnormalities {59} case 17   
                     

 


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  
  08-
U-1
female/
1m
PBL de novo 47,XX,dir dup(8)(pterq21: :q11.2qter),+mar[25%]/ 46,XX,dir dup(8)(pter→q21: :q11.2→qter),[25%]/
46,XX[50%]
r(8) different FISH-probes:
all centromeric  probes
see below {10} case 12  
multiple clinical abnormalities: small head, divergent squint, low-set posteriorly rotated ears, broad nasal bridge, epicanthic folds, anteriorly placed anus
  08-
U-2
n.a./
n.a.
n.a. n.a. 47,+mar min(8) SKY n.a. {11} case 12  
  08-
U-3
n.a./
n.a.
AF de novo n.a. min(8)(:p11.2~12q11.?2:)* acro M; M-FISH see below {14} case 11  
amniocentesis due to advanced maternal age; no clinical details available
  08-
U-4
female/
prenatal
CH and AF de novo 47,XX,+mar[7]/
46,XX[30] (= CH result)
r(8)(::p11.212q11::)
maybe it means
r(8)(::p11.2
q11::)*
centromeric probes see below {48} case 32  
CVS due to advanced maternal age; no ultrasound abnormalities; termination of pregnancy, no autopsy
  08-
U-5
see mult 2-20   {52}  
  08-
U-6
female/
prenatal
AF
(EKF-
cellbank)
de novo 47,XX,+mar[8]/46,XX[7] in culture 1;
47,XX,+mar[7]/46,XX[3] in culture 2
min(8)(:p11.21q11.21:)[8]/
min(8)(:p11.21
q11.1:)[3]/
min(8)(:p11.21
q11.1:
:q11.1
p11.21:)[1]/
r(8)(:p11.21
q11.1:
:q11.1
p11.21::q11.21::)[2]
cenM, subcenM; UPD-test Advanced maternal age; child born with 3210g, no further information available {0} provided by Dr. Sandig,
Dresden, Germany
 
  08-
U-7
see mult 2-21   {65} case NP
{66} case 16
 
  08-
U-8
male/
prenatal
AF de novo 47,XY,+mar[5]/
46,XY[8]
mar(8) wcp 8? see below {61} case 59  
Advanced maternal age; positive maternal marker serum screen; TOP
  08-
U-9
see mult 2-25   {0} provided by Dr. Mehnert, Neu-Ulm, Germany  
  08-
U-10
male/
13 m
PBL de novo 47,XY,+mar[>30%]/
46,XY
dic(8;12)(8pterq11.1:
:12q11.1
12pter)
n.a. see below {67; 104}  
psychomotoric delay, dysmorphic features like macrocephaly, agenesis of corpus callosum, high and prominent forehead, hypertelorism, dysplastic ears, cleft palate, uvula bifida, zygodactylism of 2. and 3. toes and hearing impairment
  08-
U-11
see mult 2-28   {0} provided by J. Anderson, Brisbane, Australia  
  08-
U-12
female/
prenatal
AF de novo 47,XX,+mar[60%]/
46,XX[40%]
r(8)(::p11.1q21.3::) cenM; subcenM advanced maternal age, TOP {0} provided by Lemmens, Aachen, Germany  
  08-
U-13
female/
prenatal
AF de novo 47,XX,+mar[100%] mar(8)(::p11.21q11.22::)
Array: 42.15-52.76 MB
array-CGH advanced maternal age (?), TOP {87}case 2  
  08-
U-14
male/
1y
PBL n.a. 47,XY,+mar[?%]/
46,XY[?%]
r(8) array-CGH n.a. {93} case F0451268  
  08-
U-15
female/
prenatal
AF de novo 47,XN,+mar[12]/
46,XN[2]
mar(8)(:p11.21q11.21:)
array: 39.68-48.77 MB
array-CGH advanced maternal age, TOP; autopsy: corpus callosum hypoplasia
{0} provided by Dr. C. Marchese, Torino, Italy  
  08-
U-16
female/
postnatal
PBL de novo 47,XX,+mar[20]

mar(8)(:p11.21p11.1:)
array: 40.69-43.29 MB
 

segm. UPD 8q12.1 to 8q23.1 (parental origin n.d.)

array-CGH
UPD test

DD, short stature 
{98} case 10  
  08-
U-17
 female/
prenatal
AF n.a. 47,XX,+mar[20]

mar(8)(:p12q12:)
array: 37.12-51.48 MB

iso UPD 8

 SNP-array

abnormal biochemistry, TOP; holoprosen-
cephaly

{100} case 8  
  08-
U-17
female/
10y
PBL n.a. 48,XX,+marx2[53%]/
47,XX,+mar[47%]

mar(8)
aCGH: 7,47 MB dupl.

aCGH

DD, dysmmorphic

{103}  
                     

 

 

 


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  
  08-N-
pt23.3/
1-1
female/
16y
PBL de novo 47,XX,+mar[15]/
46,XX[5]
inv dup(8)(pterp23.3:
:p23.3
pter)
pan centromeric probe; midi; locus-specific probes in 8p23 see below {31; 36; 37; 47; 71}   

Patient born after a 32-week pregnancy and uncomplicated vaginal delivery. The mother reportedly drank six to seven quarts of beer per day for two to three years and throughout the pregnancy and smoked one to two packs of cigarettes per day. She also had a psychiatric history, including treatment with trifluoperazine and chlorpromazine. Birth weight 1510 g, APGAR 7/8/-. Gavage feeding was needed for poor suck. At 20 days weight 1720 g, length 43 cm, OFC 29 cm (all <5th centile), increased hair on the forehead, camptodactyly of 5th fingers, rocker bottom feet, hypertonia with tight fisting of hands & limited extension of the elbows, knees, and hips. Weight and height were below the 5th centile throughout development. At 2-3/12 y small skull. Developmental delayed. Psychological testing at 5 y full-scale IQ score of 45 (verbal 52; performance 40; Wechsler Preschool and Primary Scale of Intelligence); moderate mental retardation; difficult to control, aggressive, and having an attention deficit at age 12-11/12. At15-5/12 y mild prominence of the ventricles; persistent spasticity in the lower limbs, with tight hamstring muscles and heel cords. Facial hirsutism at 13 y with onset of puberty; MRI at 15-2/12 y showed elongated ovaries containing multiple cysts dispersed throughout; at 15-1/12 y drooping eyelids, double vision, bumping into objects, some difficulty swallowing; Examination in the Genetics Clinic at age 15-9/12 showed: weight 41.4 kg (<5th centile; 50th centile for 12 years), height 131 cm (<5th centile; 50th centile for 7-1/2 years), OFC 56 cm (75th centile), inner canthal distance 3.2 cm (75-97th centile), ears 4.7 cm (<3rd centile; 50th centile for 9 months), hands 14.5-15 cm (<3rd centile; 50th centile for 9 years), palms 9 cm (3rd centile), and feet 19.5-20 cm (<3rd centile; 50th centile for 8 years). Facial hair was increased. There were contractures of the second, third, fourth, and fifth digits of mainly the right hand. At 16 y, persistent ptosis

 

08-N-pt
23.2~23.1/

1-1

male/
prenatal
AF/PBL de novo 47,XY,+mar[7]/
46,XY[18]
mar in 21% of PBL
inv dup(8)(pterp23.2~23.1:
:p23.2~23.1
pter)*
M-FISH, all telomeres; sub-telomere 8p, 8p22 specific probe see below {39} case 2 {71}  

Detected prenatally due to advanced maternal age; as ultrasound was normal pregnancy was continued; at 2y2m boy was physically and developmentally normal

  08-N-
pt23.1/
1-1
male/
30y
PBL de novo
(maternal? 8%)
47,XY,+mar[90%]/
46,XY[10%]
mar in 100% in fibroblasts
inv dup(8)(pterp23.1:
:p23.1
pter)
M-FISH, sub telomere 8p; all telomeres, all ceps see below {38; 71}identical with ?{26; 36; 47} unpublished case in Tab. II  

mild mental retardation and inappropriate sexual behavior, mild dysmorphism with long face and high arched palate, developmentally delayed.

  08-N-
pt23.1/
1-2
female/
2y
PBL de novo 47,XX,+mar[100] inv dup(8)(pterp23.1:
:p23.1
pter)
midi; locus-specific probes in 8p23.3 and 8p22~23.1 see below {27; 28; 36; 47; 71}  

pregnancy uneventful, delivery premature due to rupture of embryonic membrane; birth weight 2035g; 2w after birth heart murmur due to patent ductus arteriousus with pulmonary hypertension; At 2.25y weight 11.72kg, HC 50.2cm, length 86cm; broad forehead, developmental delay

  08-N-
pt23.1/
1-3
male/
8y
PBL de novo 47,XY,+mar[100] inv dup(8)(pterp23.1:
:p23.1
pter)
pan centromeric probe; midi; locus-specific probes in 8p23 see below {30} case 2 {36; 47; 71}  

Referred at 8 y for developmental delay with no obvious dysmorphic features. Observed to be good at sports but no other information regarding the patient could be obtained.

  08-N-
pt23.1/
1-4
male/
23y
PBL de novo 47,XY,+mar[25%]/
46,XY[~75%]
inv dup(8)(pterp23.1:
:p23.1
pter)
midi, wcp-FISH see below {46; 71}  

feminine stature, small testes, recurrent bone fractures, kyphosis, recurrent myocarditis, mentally normal

  08-N-
pt23.1/
1-5
n.a./
n.a.
n.a. n.a. n.a. inv dup(8)(pterp23.1:
:p23.1
pter)
n.a. n.a. {47}  
  08-N-
pt23.1/
1-6
male/
11y
PBL de novo 47,XY,+mar[~40%]/
46,XY[~60%]
inv dup(8)(pterp23.1:
:p23.1
pter)
pan centromeric probe; midi; locus-specific probes in 8p23 see below {30} case 1
{36; 47; 71}
 

first referred at 2 months of age for failure to thrive, no palpable testis, bilateral inguinal hernia; born at term by emergency caesarean section after arrested breech; heart murmur at birth - later found to be patent ductus arteriousus; microphallus, bilateral undescended testes, bilateral inguinal hernia, recurrent bronchiolitis, milk allergy and asthma. At age 2 years and 6 months height below 3rd centile; weight between 3rd and 10th centile. At age 9 Attention Deficit Hyperactivity Disorder; below average intellectual ability. At 13y, short stature (below 3rd centile), delayed puberty, continued behavioral problems, IQ of 75.

  08-N-
pt23.1/
1-7
n.a./
n.a.
n.a. n.a. 47,+mar[?%] inv dup(8)(pterp23.1:
:p23.1
pter)
n.a. n.a. {75}  
  08-N-
pt23.1/
2-1
female/
4y
PBL de novo 47,XX,+mar[100%] der(8)(pterp23.1::p23.3p23.1:)
array: 0.0-6.79MB
FISH array-CGH clinically abnormal {0} provided by Dr. Heinrich, Martinsried  
  08-N-
pt23/
1-1
female/
postnatal
PBL n.a. 47,XX,+mar[21]/
46,XX[6]
inv dup(8)(pterp23::p23pter)[7]/
r(8)(::pter
p23::)[8]/
min(8)(pter
p23:)[6]
CGH, array CGH; MCB slight mental retardation {101}  
  08-N-
pt23/
1-2
n .a./
postnatal
PBL n.a. 47,XN,+mar[?100%] inv dup(8)(pterp23::p23pter) FISH n.a. {102}  
  08-N-
pt22/
1-1
female/
prenatal
AF/
PBL
de novo 47,XX,+mar[3]/
46,XX[14]
mar in 50% of PBL
inv dup(8)(pterp22:
:p22
pter)
midi, band-specific probes see below {45; 71}   

Amniocentesis due to advanced maternal age. Patient born at week 41 after normal pregnancy; Birth weight: 3410g, APGAR 9/10; no dysmorphism seen at birth. At 8m minor epicanthal fold on the left side and hemangiomas on right temple. No developmental delay

  08-N-
pt22/
1-2
n.a./
n.a.
n.a. n.a. n.a. inv dup(8)(pterp22:
:p22
pter)
n.a. n.a. {47}   
                     

 

 

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  
  08-
N-IMB-
p23/
1-1 to
 1-48
48 case with partial trisomy 8p are summarized in Ref {68} - also see {72-73}
see also {77}
{68}  
  08-
N-IMB-
q23/
1-1
1 case with 3y dysmorphic, mental retardation, hyperekplasia
see also {80}
{76}