SMALL SUPERNUMERARY MARKER CHROMOSOMES- sSMC 8 -
|
| Cases without clinical findings |
15 |
Cases with clinical findings |
62 |
symptoms |
| Cases with iso-chromosome 8p |
20 | |||
| Cases with unclear clinical correlation |
Cases with neocentromeres |
13 |
tumor 0 |
|
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
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 48.30 --- 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 48.12 --- 52.74 critical region
Clinical symptoms of centromere-near proximal imbalances
|
chromosomal region |
8p - proximal | 8q - proximal |
| symptoms | ||
| autism | 26 % | 0 % |
| brain malformations | 7 % | 0 % |
| developmental delay | 81 % | 80 % |
| dysmorphic face | 38 % | 100 % |
| finger or toe/foot malformations | 13 % | 40 % |
| hearing problems/ loss (sensor neural) | 7 % | 20 % |
| heart defect | 7 % | 0 % |
| hip problems | 7 % | 0 % |
| hypotonia | 13 % | 20 % |
| joint problems | 13 % | 0 % |
| macrocephaly | 7 % | 0 % |
| mental retardation | 38 % | 20 % |
| microcephaly | 0 % | 20 % |
| overgrowth | 13 % | 0 % |
| seizures | 7 % | 0 % |
| urethral problems | 0 % | 20 % |
| number of cases (marked with “°” below) | 16 | 5 |
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 | ||
| r(8)(::p23.1→q1?1::)/*r(8;8)(::p23.1→q1?1::p23.1→q1?1::), proportion unknown | ||||||||||
| 08-O- p11.22~ 11.21/ 1-1 |
female/ prenatal |
AF | n.a. | 47,XX,+mar[67%]/ 46,XX[33%] |
min(8)(:p11.22~11.21→q11.1:) FISH-data: 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 |
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| 08-O- p11.21/ 1-1 |
female/ prenatal |
AF | maternal | 47,XX,+mar[43]/ 46,XX[7] |
r(8)(::p11.21→q11.1::) 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 |
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| 08-O- p11.21/ 1-2 |
male/ prenatal |
AF | n.a. | 47,XY,+mar[25] 46,XY,[2] |
r(8)(::p11.21→q11.11::) 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 |
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| 08-O- p11.21/ 2-1 |
male/ 30y |
PBL | n.a. | 47,XY,+mar[44]/ 46,XY[6] |
min(8)(:p11.21→q11.1:) FISH-data: RP11-503E24 at 42.5MB on sSMC |
cenM;subcenM | see below | {0} provided by Jasen Anderson, Brisbane, Australia | ||
|
normal male - with fertility problems |
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| *** 08-O- p11.21/ 3-1 *** |
female/ prenatal |
AF | n.a. | 47,XX,9ph+,+mar[15] 46,XX,9ph+[10] |
r(8)(::p11.21→q11.21::) FISH-data: RP11-503E24 at 42.5MB and RP13-116A4 at 48.3MB on sSMC |
cenM;subcenM | see below | {0} case provided by Dr. Schliephacke, Linden, Germany | ||
|
Amniocentesis due to advanced maternal age; normal child born; normal at 14m of age |
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| 08-O- p11/ 1-1 |
female/ prenatal |
AF | de novo | 47,XX,+mar[16]/ 46,XX[7] |
min(8)(:p11→q11:) | 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 |
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| 08-O- p11/ 1-2 |
female/ prenatal |
AF | de novo | 47,XX,+mar[33]/ 46,XX[2] |
min(8)(:p11→q11:) 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 |
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| 08-O- p11.1/ 1-1 |
male/ 44y |
PBL | n.a. | 47,XY,+mar[7]/ 46,XY[10] |
min(8)(:p11.1→q11.21:)[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)(::p11→q11.2::) FISH-data: RP13-116A4 at 48.3MB on sSMC |
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)(::p10→q12::) | 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?1.2→q1?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 |
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| 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)(::p11→q11::)* | centromeric probes | advanced maternal age + anxiety; normal girl born and still normal at 6y | {48} case 3 | ||
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} |
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|
mental retardation, hypotonia; wide mouth; slender fingers, height and weight <3rd centile |
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| 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 |
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| 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} | ||
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)(:p23.3→p23.3: :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
|
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| 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)(::p23.1→q10::)* | 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- p21.2/ 1-1 ° |
male/ 7y |
PBL | de novo | 47,XY,+mar[30%]/ 46,XY[70%] interphase FISH 50%, each |
min(8)(:p21.2→q11.1:) 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)(?::p12→q11.1: :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)(::p12→q12::) | 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)(:p12→q10:)* | 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)(:p12→q11.1:) 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)(:p12→q11.23:)* 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?.2→q11?.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)(::p11.2→q12::)[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)(::p11.2→q12::) | 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)(:p11.2→q11.2:)[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)(::p11.2→q13~21.1::) | 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)(::p11.23→q11.21: :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)(:p11.23→q11.21:) 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)(:p11.23→q11.21:) 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)(:p11.23→q11.1:) aCGH: 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)(:p11.22→q11.22:)* 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 |
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| 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 |
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| 08-W- p11.22/ 2-1 |
male/ postnatal? |
PBL? | n.a. | 47,XY,+mar[57%]/ 46,XY[43%] |
mar(8)(:p11.22→q11.1:) | 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)(::p11.21~11.22→q11.1::) FISH-data: 42.5-49.5 MB |
cep probes; BACs, subcenM; UPD-test | see below | {0} | ||
| 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)(:p11.21→q11.1:)* | 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)(:p11.21~11.22→q11.1:)* | 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)(:p11.21~11.22→q10:)* 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)(:p11.21→q11.1:) 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)(:p11.21→q11.1:) 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)(:p11.21→q11.21:)* | 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)(:p11.21→q11.21:) FISH-data: RP11-503E24 at 42.5MB and 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)(:p11.21→q11.21:) 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)(::p11.21→q11.1: :p11.21→q11.1::) FISH-data: RP11-64C22 at 42.5MB on sSMC |
cenM; subcenM |
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)(:p11.21→q11.1: :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)(::q10→p11.2: :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)(::p11→q11::)* | 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)(::p11→q11::) | 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)(::p11→q11.2?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)(:p11.1→q11.21:)[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: :p11.1→q11.21:)[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 |
M-FISH; subcenM; MCB |
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)(:p11.1→q11.23:) 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)(::p10~11.1→q11.21::) 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)(::p10~11.1→q11.21::)* 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)(:p11.1→q21.?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 | de novo | 47,XY,+r[15] | r(8)(::p10→q23.3::) | 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 | ||||||||||
| 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)(::p10→q21.1::) | 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)(pter→q11::p11.2?3→qter)[16]/45,XY,-8[4] | subcenM | see below | {0}provided by Dr. Hasmik Mkrtchyan, Yerevan, Armenia | ||
|
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. |
||||||||||
| 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 | ||
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)(pter→q21: :q11.2→qter),+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)(:p11.2~12→q11.?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)(::p11.2→12q11::) 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 | de novo | 47,XX,+mar[8]/46,XX[7] in culture 1; 47,XX,+mar[7]/46,XX[3] in culture 2 |
min(8)(:p11.21→q11.21:)[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)(8pter→q11.1: :12q11.1→12pter) |
n.a. | see below | {167} | ||
| 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)(::p11.1→q21.3::) | 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)(::p11.21→q11.22::) 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 | ||
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)(pter→p23.3: :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 |
male/ prenatal |
AF/PBL | de novo | 47,XY,+mar[7]/ 46,XY[18] mar in 21% of PBL |
inv dup(8)(pter→p23.2~23.1: :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 |
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| 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)(pter→p23.1: :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. |
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| 08-N- pt23.1/ 1-2 |
female/ 2y |
PBL | de novo | 47,XX,+mar[100] | inv dup(8)(pter→p23.1: :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 |
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| 08-N- pt23.1/ 1-3 |
male/ 8y |
PBL | de novo | 47,XY,+mar[100] | inv dup(8)(pter→p23.1: :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. |
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| 08-N- pt23.1/ 1-4 |
male/ 23y |
PBL | de novo | 47,XY,+mar[25%]/ 46,XY[~75%] |
inv dup(8)(pter→p23.1: :p23.1→pter) |
midi, wcp-FISH | see below | {46; 71} | ||
|
feminine stature, small testes, recurrent bone fractures, kyphosis, recurrent myocarditis, mentally normal |
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| 08-N- pt23.1/ 1-5 |
n.a./ n.a. |
n.a. | n.a. | n.a. | inv dup(8)(pter→p23.1: :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)(pter→p23.1: :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. |
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| 08-N- pt23.1/ 1-7 |
n.a./ n.a. |
n.a. | n.a. | 47,+mar[?%] | inv dup(8)(pter→p23.1: :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)(pter→p23.1::p23.3→p23.1:) 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)(pter→p23::p23→pter)[7]/ r(8)(::pter→p23::)[8]/ min(8)(pter→p23:)[6] |
CGH, array CGH; MCB | slight mental retardation | {0}case provided by Dr. C. Fuster, Spain | ||
| 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)(pter→p22: :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 |
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| 08-N- pt22/ 1-2 |
n.a./ n.a. |
n.a. | n.a. | n.a. | inv dup(8)(pter→p22: :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} | |||||||