ChromosOmics - Database

Icon by Leon Liehr                   

                                                  -  CHROMOSOME #8 -                                                 
ABNORMAL

  Specific PATIENTINFORMATION for sSMC(8) - part 1
Specific PATIENTINFORMATION for sSMC(8) - part 2

Cases without clinical findings
 Similar imbalances – no sSMC
Cases with
clinical findings
Similar imbalances -
no sSMC 
sSMC
not well characterized
Cases with isochromosome 8p
Cases without clear clinical correlation
Cases with discontinous sSMC
Cases with complex sSMC
Cases with UPD and sSMC
Cases (sSMC) with neocentromeres
Similar imbalances - no sSMC
Tumor
DISCLAIMER

References


In general 70% of sSMC carriers are clinically normal. The figures listed above

are based on the bias, that mainly clinically aberrant cases are studied and reported in literature!
UPD (uniparental disomy) cases: UPD(8)mat UPD(8)pat UPD(8)mat or pat

Cases with isochromosome 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 test MR, hypotonia; wide mouth; slender fingers, height and weight <3rd centile {5} case 6
{6}
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 see below {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-test 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) aCGH 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)		 aCGH; FISH agenesis of corpus callosum, bilatheral colpocephaly, IUGR, TOP {88}
08-
W-
iso/
1-21		 male/
newborn		 PBL n.a. 47,XY,+mar[45]
46,XY[5] 		i(8p)
break in 8q13; at 78.6Mb		 aCGH agenesis corpus callosum, low muscle tone MR,DD {112} case A
08-
W-
iso/
1-22		 male/
7y		 PBL n.a. 47,XY,+mar[4]/
46,XY[46]
i(8p)		 FISH
DD		 {0} provided from Germany
08-
W-
iso/
2-1		 male/
14y		 PBL n.a. 47,XY,+mar[14]/
46,XY[6]
i(8p)		 subcenM-
FISH		 normal apart from dwarphism {120}

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		 see 08-Ud-1
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-
p23.1/
2-1
°°°
 female/
6y		 PBL de novo 47,XX,+mar[20]/
46,XX[10]		 r(8)(::p23.1→q12::)
NGS-data [hg19]: 9,803,437-56,519,601
no UPD - sSMC of mat origin		 NGS
UPD test		 psychomotor delay {119} case sSMC8b

08-
W-
p22.1/
1-1		 male/
prenatal		 AF/PBL de novo 47,XY,+mar[3]/
46,XY[37]		 r(8)(:p22.1→q12.1:)
aCGH-data: 18.10-61.10 Mb		 M-FISH,
aCGH,
UPD-test		 amniocentesis due to fetal pyelectasis in 2. trimester; normal child born appart from mild bilatheral hydronephrosis {99}
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 from 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-
p21.2/
1-2
°°°
 male/
14y		 PBL n.a. 47,XY,+mar[40%]/
46,XY[60%]		 min(8)(:p21.2→q11.1:)
aCGH (hg19) 26,417,000-43,000,000		 aCGH
subcenM		 DD {0} provided from Germany
08-
W-
p21/
1-1		 female/
5y		 PBL de novo 47,XX,+mar[50%]/
46,XX[50%]		 see below midi, subcenM-FISH,
all human telomeres; aCGH		 agenesis corpus callosi, deep set , malrotated ears, DDfacial DYS, psychomotor and {0}
{50} case 8-1; {62} case D
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→q11.21:),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}
08-
W-
p12/
1-1
°°°
 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 and 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 Mild MR, labile attention, tachyphemic speech and dyslalia, DD {0} provided from Spain
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)		 aCGH DD, DYS {64} case 5
08-
W-
p12/
4-2		 male/
3y		 PBL de novo 47,XY,+mar[24]/
46,XY[6]		 min(8)(:p12→q11.23:)
aCGH: 36.02-54.24 Mb		 cenM, subcenM; aCGH DD, microcephaly, speech delay {0}
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		 aCGH
cep 8
BAC-FISH		 VSD in sonography, micrognathia, TOP {84}
08-
W-
p12/
6-1		 see 08-Ud-2
08-
W-
p12/
7-1		 male/
prenatal		 AF
PBL		 de novo AF: 47,XY,+mar[20]/
46,XY[39]
PBL: 17:23		 r(8)(::p12→q13.1::)
array-data (hg18 or 19):
3,476,753-67,428,722		 aCGH, FISH, UPD-test see below {116}
at 30 weeks of gestation showed bilateral ventriculomegaly, intrauterine growth restriction, and an enlarged rightatrium. Birth weight 2380g mild facial dysmorphism of large ears, full cheeks with medial aring of eyebrows, epicanthic folds, brachycephaly
08-
W-
p12/
8-1		 female/
27y		 PBL n.a. 47,XX,+mar[60]/
46,XX[40]		 r(8)(:p12→q21.13:)
aCGH (hg19): 36,013,636-81,263,140
 aCGH congenital hypoplasia of the tongue {124}
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, a broad nasal bridge, and a small mouth. At 1½y, weight 7.9 kg (<3rd centile), length 77 cm (<3rd centile), head circumference 44 cm (<3rd centile), small right kidney with right hydronephrosis, hypospadias ; normal vision / hearing, but could not follow the orders; strabismus, hypotonia, DD, and mild mental retardation. brain ultrasound arachnoid cyst.
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, aCGH, subcenM, BACs see below {0} provided from Spain
MR, 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 from 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, MR {0} provided from Germany
08-
W-
p11.2/
2-2
°°°
 female/
3y		 PBL mat/ grand-
mat		 47,XX,+mar[100%] mar(8)(:p11.2→q11.21:)
aCGH: size 9.1 Mb		 aCGH; centromeric and pericentric probes; see below {107}
whole family with similar symtoms; delayed psychomotor development, intellectual disability, behaviour disorder and autistic spectrum disorder without associated dysmorphism or malformations
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 from Brazil
08-
W-
p11.23/
1-1		 see 08-Ud-3
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		 aCGH severe hypotonia; hypospadias {90} case P-4
08-
W-
p11.23/
2-2		 female/
1y		 bone marrow / bucchal mucosa pat
in bucchal mucosa: 47,XX,+mar[38%]/
46,XX[62%]		 min(8)(:p11.23→q11.21:)
array-data: 36.67-50.14 MB (? hg19)		 aCGH frontal bossing, downslanting palpebral fissures, hypertelorism, low nasal bridge; JMML {94; 95} case D703
08-
W-
p11.23/
2-3		 female/
15y		 PBL n.a.   47,XX,+mar[50%]/
46,XX[50%]		 min(8)(:p11.23~p12→q11.21:)
 subcenM attention deficite disorder
 {0} provided from Germany
08-
W-
p11.23/
2-4		 male/
2y		 PBL mat
(3/100 cells)
   47,XY,+mar[20%]/
46,XY[80%]		 min(8)(:p11.23~p12→q11.21:)
aCGH [hg19:]:
36,919180-50,674599 		FISH, aCGH
 infantile seizures, acute bronchitis, myocardial injury, hepatic failure, anemia, and eczema, intellectual disability, speech retardation, and muscular dystonia
 {127}
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; aCGH global DD, autism, and low muscle tone {92} case 7
08-
W-
p11.23/
3-2
°°°
 male/
7y		 PBL n.a. 47,XY,+mar[100%] min(8)(:p11.23→q11.1:)
aCGH (hg19): 38,61-40,03MB		 aCGH
subcenM		 DD, DYS, hemiparesis {0} provided from Germany
08-
W-
p11.23/
3-3
°°°
 male/
2y		 PBL de novo 47,XY,+mar[100%] min(8)(:p11.23→q11.1:) cenM; subcenM; 1Mb set DD, DYS {0} provided from Hungary
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; aCGH; 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)(:p11.22→q11.1:) aCGH abnormal {85} case 26750
08-
W-
p11.22/
3-1		 see 08-Ud-7
08-
W-
p11.22/
4-1		 see 08-Ud-4
08-
W-
p11.22/
5-1		 male/
6y		 PBL
n.a.		 47,XY,+mar[50%]/
46,XY[50%]		 mar(8)(:p11.22→q11.23:)
size 13.8 Mb		 aCGH DD, behavior problems, corpus callosum
hypoplasia, minor dysmorphic features		 {111}
08-
W-
p11.22/
6-1		 female/
18y		 PBL de novo 47,XX,+mar[22]/
46,XX[18]		 r(8)(::p11.22→q11.21::)
array-data (hg18 or 19):
39,136,065-49,725,726		 aCGH; FISH
UPD test		 see below {115}
Birth weight 3060 g. At 18y short stature (147.7 cm), obesity (65.5 kg), psychomotor DD , speech delay, dyslexia, ADHD since youth, intellectual disability, and mild mental retardation. Also small breasts, scanty pubic hair, low posterior line, and cubitus valgus
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
{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)(:p11.21→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 DD {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
aCGH		 DD {64} case 3
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 from 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 DD		 {0} provided from 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, DD, 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 DD {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)		 aCGH, Interphase-FISH mild psychomotor delay; detected due to JMML {94} case D600
08-
W-
p11.21/
2-4		 female/
1y		 PBL n.a. 48,XX,+marx2[53%]
47,XX,+mar[47%]		 min(8)(:p11.21→q11.21:)
array-data: 41.11-48.59 MB (hg19)		 aCGH DD, MR, microcephaly, DYS, hypotonia {114}
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
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)(:p11.21→q11.1:
:q11.1→p11.21:)		 cenM;
subcenM		 see below {0} provided from Russia
Moderate MR, 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!?)		 aCGH DD {64} case 4

08-
W-
p11.21/
5-1 		male/
postnatal		 PBL n.a. 47,XY,+mar[47]/
46,XY[36]		 r(8)(::p11.21→q21.13::)
size: 43.92 Mb		 aCGH see below {110}
DD, multiple congential abnormalities, thoracolumar scoliosis, mild pulmonary stenosis, laryngomalacia, hypospadias and atypical facial appearance
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
MR and behavioral problems at age of 2y. At 8y mild MR, proportionate general build, no major malformations, mild lydysmorphic deep-set eyes and 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 mild intellectual delay but no dysmorphic features {39} case 1
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}
DD, 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]		 see below M-FISH;
subcenM;
MCB;
aCGH		 see below {50} case 8-9
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
aCGH: 8q11-8q11.23 (47,631,690-53,095,051 Mb)
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;
aCGH; UPD-test		 DD; DYS {0} provided from France
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
AMA, omphalocoele, TOP		 {0} provided from 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		 aCGH 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 from Russia
DD, hip dysplasia, cardiomyopathy, partial right ptosis, congenital stridor, short neck, epicantic folds, low-set dysplastic ears, frontal bossing, broad/flat nasal bridge
08-
W-
p11.1/
6-1
°°°
 male/
1y		 PBL n.a. 47,XY,+mar[6]/
46,XY[9]		 min(8)(:p11.1→q21.11:)
aCGH (hg19): 47.51-76.11 Mb		 cenM;
subcenM;
aCGH		 DD, DYS, muscular hypotonia, simian crease {0}
08-
W-
p10/
1-1		 male/
1.5y		 PBL
(EKF-
cellbank)		 de novo 47,XY,+r[15] r(8)(::p10→q23.3::) cenM;
MCB		 see below {0} provided from 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)(::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 and final FISH result test
methods
 		clinical symptoms
 		Reference
08-
W-
IMB-
q12/
1-1
°°°
 female/
8y 		PBL n.a. 46,XX,dup(8)(q12) not specified severe MR, narrow forehead, prominent metopic suture, postaxial polydactyly of fingers, sacral sinus, hypotonia; at 1 and 4 y left and right Wilmstumor {79}
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 microcephaly, autism, DD, dysmorphic face, joint problem; MR , chest deformation {96}

W-cases with unclear/insufficient characterization of the sSMC (CW)

case no.
 		gender/
age at diagnosis
studied
material
 		de novo/
inherited
 		GTG-banding result
grade of mosaicism
 		final result of the sSMC
 		test
methods
 		clinical symptoms
 		Reference
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]		 ish min(8)(wcp8+) 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]		 ish min(8)(D8Z1+) midi; cep8 (D8Z1) growth retardation at 9y; normal psychomotor development; idiopathic non familiar short stature {33}
08-
CW-
4		 male/
10y		 PBL de novo 47,XY,+mar[100%] ish min(8)(cep8+) several cep probes monorchidism, cryptorchidism, mental retardation {34-35 case 2}
08-
CW-
5		 male/
n.a.		 n.a. n.a. 47,XY,+mar[100%] min(8) SKY DYS; DD {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 aCGH
 DD, severe intellectual delay, mild ataxia, DYS {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} case7
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 DD 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 aCGH 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)(cep8+; GATA4(8p23.1)+, telomere+ telomeric probe; all wcp in aCGH; GATA 4 infertility , mMR (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,[nbsp] 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 ([lt]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 AMA;  abnormal triple test and ICSI. TOP, congenital heart abnormalities {59} case 17