ChromosOmics - Database

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                                                  -  X-CHROMOSOME -                                                 
ABNORMAL
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
0X-
W-
p21/
2-1		 see McCl-0X-W-p21/2-1
0X-
W-
p11.?3/
1-1		 male/
postnatal		 PBL n.a. 47,XY,+mar[100%] min(X)(:p11.?3→q11.1:)[1]/
min(X)(:p11.1→q11.1:)[2]/
min(X)(p11.2?2→q11.1:
:q11.1→p11.1:)[4]/
min(X)(:p11.1~q11.1:
:q11.1→p11.1:)[6]		 CGH, HR-CGH; subcenM multiple malformations {41}
0X-
W-
p11.3/
1-1		 male/
prenatal		 CVS; PBL de novo 47,XY,+mar[9]/
46,XY[11]		 r(X)(::p11.3→q13.1::)
included in sSMC: RP11-386N14 (44.54 MB) to RP11-446J19 (68.63 MB); XIST not included		 aCGH see below {42}
In pregnancy in week 12 a cystic hygroma was noted in the fetus. Normal growth until week 32, then mild IUGR. At birth weight 2.27 kg (3rd percentile) length 45cm (10th percentile). Unusual facial features, limb anomalies, and undescended testicles. Neonatal problems: initial low blood glucose and poor temperature regulation. At day 5 sent home in good condition. With 2 months poor weight gain, slow feeding with poor caloric intake, and hypotonia. All growth parameters [lt]5th percentile for age, very wide midface, bifid flame nevus on his forehead, hypertelorism, epicanthal folds, mild proptosis with shallow orbits, roving eye movements but intact extraocular movements, bifid and upturned nasal tip, and anteverted nares, ears low set and posteriorly rotated with simplified helices and pits on both lobes, mouth small and asymmetric with apparent intact orbicularis oris muscle function and no facial palsy; Oral cavity revealed a high-arched palate without clefting and a prominent median lingual frenulum; mild pectus excavatum, hypospadias with normal-sized phallus and bilateral cryptorchidism, shallow sacral dimple, and a narrow but patent anus, limb anomalies that included broad thumbs, bilateral 3,4 cutaneous syndactyly, normal palmar creases, and distal limb asymmetry. The left foot had a broad great toe which deviated medially and 3,4 syndactyly; right foot 2,3 syndactyly and a normal great toe. Skin examination was pertinent for whorls and streaks of hyperpigmentation over trunk, flame nevus. Abdominal ultrasonography: single left kidney and patent ductus arteriousus (deemed hemodynamically insignificant at that time). Magnetic resonance imaging of brain: small anterior body of the corpus callosum with absence of the posterior body, splenium, and rostrum and a prominent, high-riding third ventricle; radiograph of the upper gastrointestinal tract showed severe gastroesophageal reflux; subsequently found to have vesicoureteral reflux and was admitted to the hospital at the age of 8 months for urologic surgery including exploratory cystoscopy, ureter reimplantation, bilateral orchidopexy with inguinal hernia repair, and release of chordee tendinae. A presumed ectopic ureter entering the bladder neck near the verumontanum with no renal attachment was noted and removed. Pathologic evaluation revealed that this tissue was in fact a rudimentary cervix and uterus with bilateral fallopian tubes. No ovarian structures were noted. He underwent a respiratory arrest a few days after surgery and had a complicated hospital course requiring prolonged ventilator support. At 1 year (Fig. 1B) at which time he was noted to have similar physical features to his previous evaluation at the age of 2 months. He was making slow developmental progress and gaining some new skills.
0X-
W-
p11.22/
1-1		 male/
3y		 PBL de novo 47,XY,+mar[22]/
46,XY[8]		 min(X)(:p11.22→q11.1~11.2:)* SKY, locus specific probes, aCGH see below {29}
Patient at birth 2920g, 47cm long and OFC 34.1cm. At 3y mental retardation, speech delay, height 96.7cm, hyperactivity, no speech, hypertelorism, arched eyebrows, epicantal folds, low-set ears, short nose, depressed nasal tip, long philtrum, small mouth, clinodactyly of both 5th fingers, syndactyly of left second and third toes.
***
0X-
W-
p11.22/
1-2		 female/
3y		 PBL de novo 47,XX,+mar[30] min(X)(:p11.22→q11.1:)*
distal breakpoint in Xp: 50.9MB		 SNP aCGH
 see below {39}
Normal pregnancy. Birth weight 2,750 g (10th centile), length 49 cm (50th centile), head circumference 33.5 cm (25th centile). Mild hypertelorism at birth. At 12 months hypotonia and global developmental delay; first walked at age 21/2 years. At age 3 years had no distinguishable words, but able to follow simple instructions, feed herself with finger-food and hold a cup with two hands. There was no developmental regression; weight 16.3 kg (95th centile), length 92.4 cm (25th centile), and head circumference 47 cm (25th centile). Facial features: broad forehead, hypertelorism, down slanting palpebral fissures, prominent and anteverted alar nasae, prominent nasolabial groove, thin vermillion border, and low set ears, disorganized dentition and an intact palate; genu valgum and bilateral single palmar creases, with short fingers and tapering thumbs, short great toes and 4th toe clinodactyly. Genitalia and anus were normal. She was hypotonic but her neurological examination was otherwise normal.
0X-
W-
p11.22/
2-1		 male/
9y		 PBL n.a. 47,XY,+mar[8]/
46,XY[7]		 r(X)(::p11.22→q12::) ceps,
subcenM
PCeR-FISH		 DD, facial dysmorphisms {0} provided from Germany
0X-
W-
p11.21/
1-1		 male/
13y		 PBL n.a. 47,XY,+mar[100%] FISH: min(X)(:p11.21→q10:)[4]/
min(X)(:p11.21→q10:
:q10→p11.21:)[8]/
r(X)(::q10→p11.21:
:q10→p11.21::)[2]
aCGH revised: 55,652,680-64,349,995 MB		 cenM; subcenM; aCGH Patient with non-specific mild-to-moderate MR, with a normal phenotype, except for some hypotonia. The parents also have a mental handicap {27}case X-1;
{31} case C
0X-
W-
p11.21/
2-1		 female/
11y		 PBL/ fibroblasts de novo 47,XX,+mar[40]/
46,XX[8]
25/13 in fibroblasts		 min(X)(:p11.21→q11.1:)* all available centromeric probes; wcpX; 7 pericentric probes as specified in {22} see below
{22} case 2
Pregnancy was complicated by hypertension, delivery normal. Birth weight 2,400 g; length 48 cm. She developed grave hyperbilirubinemia and had an exchange transfusion. Poor feeding present in neonatal period. Failure to thrive until age 6 months followed by increasing weight gain and obesity after 3 years, which has persisted. At 3 years myopia (-10 diopt.) was noted. At years was found to be severely retarded with a developmental age of approximately 3 years. At age 20 years, a seizure occurred and EEG was found to be abnormal. She was assessed by a psychiatrist due to regression as well as aggressive and impulsive behavior =[gt] Atypical mood disorder. Behavior always restless and unfocused, sometimes aggressive. Pubertal development was normal. Minor anomalies include hypertelorism, small nose, epicanthus, low hairline in the neck, ‘‘carp-shaped’’ mouth, lordosis, genua valga, small hands, and small feet. Deletion in the Prader-Willi critical region (15q11) was excluded by FISH
0X-
W-
p11.21/
3-1		 female/
1y		 PBL de novo 47,XX,+mar[60%]/
46,XX[40%] acc. to {9}
66%/34% acc. to {22}		 min(X)(:p11.21→q11.2:)* all centromeric, wcpX; 7 pericentric probes as specified in {22} see below {9}
{22} case 1
born at term (weight 2200g, length 49cm); seizures at 1y, at 12y moderate mental retardation and impaired speech. Dysmorphic face: telecanthus, hypertelorism, low-bridged nose, small mouth, micrognathia, high-arched palate. Small hands and feet, fingers were tapering with hypoplastic nails and left clinodactyly. Obese with weight >97th centile.
0X-
W-
p11.21/
4-1		 male/
2.5y		 PBL de novo 47,XY,+mar[50] r(X)(::p11.21→q12::)*
(XIST not present on sSMC)		 FISH with different YAC probes as specified in {14} see below {14} case 1
Patient born after uneventful pregnancy without complications; at 2.5y global developmental delay, HC at 2.5y on 10. centile; dysmorphic with moderate scaphocephaly, long philtrum, flattened nose, high arched palate, crowded dentations
0X-
W-
p11.21/
4-2		 female/
9y		 PBL n.a. 47,XX,+mar[10]/
46,XX[20]		 r(X)(::p11.21→q12::) midi; subcenM dwarphism, minor facial DYS {0} provided from Germany
0X-
W-
p11.21/
5-1		 male/
newborn		 PBL ?de novo 47,XY,+r[7]/
46,XY[23]		 r(X)(::p11.21→q13.1::)
aCGH: 55,260,049-68,590,017 MB		 aCGH, BACs Craniofrontonasal syndrome (CFNS) caused by inactivating mutations in the gene for ephrin-B1 (EFNB1) {43}
0X-
W-
p11.2/
1-1		 male/
11y		 PBL de novo?
(father n.a. for study)		 47,XY,+mar[70%]/
46,XY[30%]		 r(X)(::?p11.2?→q12::)
(XIST not present on sSMC)
FISH showed sSMC in 251/392 metaphases)		 FISH with different YAC probes as specified in {15} see below {15; 35 case 2}
Patient with clumsiness and learning disabilities at age of 11y; mild myopia, speech normal, coordination poor; external genital immature; height between 75.-90. centile at age of 14y; father with learning disabilities, too;
0X-
W-
p11.2/
2-1		 female/
13y		 PBL n.a. 47,XX,+mar[4]/
46,XX[14]		 min(X)(:p11.2→q12:) cenM, subcenM see below {0} provided from Russia
DD (problems with school education), hypoplasia of left kidney, hydronephrosis of right kidney, epicanthus, hypertelorism of eyes, dysplastic ear auricles, seliform nosal bridge, high-arched palate, short neck, valgus deformation of legs, hypermotility of joints, hirsutism, cyst in the left ovary, partially clinical picture of Turner syndrome (especially concerning gonads, but there is no growth retardation).
0X-
W-
p11.2/
3-1		 female/
19y		 PBL n.a. 47,XX,+mar[8]/
46,XX[42]		 r(X)(::p11.2→q13.3::)
aCGH: 63,541,782-71,253,149		 cenM subcenM, XIST; aCGH DD {0} provided from Australia
0X-
W-
p11.1/
1-1		 female/
postnatal?		 PBL? n.a. 47,XX,+mar[27%]/
46,XX[73%]		 mar(X)(:p11.1→q21.1:) aCGH abnormal {40} case 32374
0X-
W-
p11/
1-1		 male/
prenatal		 CH de novo 48,XY,+r,+r[6]/
47,XY,+r[10]/
46,XY[4]
(figures given for short term culture; in long term culture: 18/22/10)		 r(X)(::p11→q12~13.1::)* all available centromeric probes; wcpX; XIST-probe ; pericentric YAC probes (see {13}) see below {13}
Chorion biopsy as fetal nuchal translucency present: thickness 4mm in week 12; in week 20 ultrasound revealed Dandy-Walker malformation with vermian agenesis, agenesis of corpus callosum and septal pellucidum, dilated ventricles; pregnancy terminated; fetopathology showed cerebral midline defects associating complete corpus callosum and septal agenesis, Dandy-Walker malformation, enlarged ventricles, dysmorphic like brachycephaly, hypertelorism, depressed nasal root, anteverted nares, cleft palate; marker presence confirmed in fetal tissue
0X-
W-
p11/
2-1		 female/
5y		 PBL n.a. 47,XX,+mar[25%]/
46,XX[75%]		 min(X)(:p11.1→q11:)
possibly slightly larger - hard to determine by midi alone		 midi delayed speech, hands dysmorph, double kidney left {0} provided from Germany
0X-
W-
p11/
3-1		 male/
18y		 PBL n.a. 47,XY,+mar[39%]/
46,XY[61%]		 min(X)(:p11.1→q11:) cep XIST Klinefelter-phenotype {0} provided from Germany

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
0X-
W-
IMB-
q11.2/
1-1
male/
postnatal 		PBL maternal (on inactivated X) 46,XY
aCGH: triplication in Xq11.2
62.66-63.41 MB 		aCGH see below {38}
Patient had a condition resembling the neonatal form of spinal muscular atrophy, including extreme hypotonia, lack of reflexes, no suck or swallow, little to no movements, and congenital contractures. He died of respiratory failure at 3 weeks of age. His autopsy showed severe muscle fiber atrophy with prevalence of myofibrillar disorganization consistent with a lower motor unit disorder. The spinal cord had rare anterior horn cells with alterations suggestive of early chromatolysis.
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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
0X-
CW-
 1		 male/
2m		 PBL de novo 47,XY,+mar[?%]/
46,XY[?%]		 min(X) all available centromeric probes; wcpX see below {10}
pregnancy uneventful, delivery prolonged and terminated by vacuum extraction; APGAR 8/9/10; weight: 3450g, length: 55cm, HC: 36cm; inguinal hernias and cryptorchidism; mild enlarged ventricles detected by brain ultrasound; adducted, low-set thumbs, dysplastic ears, hemangiomas of the upper eyelid, alae nasi and philtrum; severe motor and mental retardation
0X-
CW-
2		 male/
prenatal		 AF de novo 47,XY,+mar[50%]/
46,XY[50%]
mar present in ~80% of PBL		 min(X)(:p?→q13.1:)* all available centromeric probes; wcpX; XIST-probe birth at term, boy with deep-set ears, arachnodactyly, hyperextension of head, micropenis. {12} case 38
0X-
CW-
3		 female/
4m		 PBL de novo 47,XX,+r[23]/
46,XX[77]		 r(X) cep X; XIST probe see below {21}
pregnancy and birth normal; normal birth weight and length; later feeding problems and failure to thrive; hypotonia, developmental delay; minor anomalies, retromicrognathia, gastrointestinal reflux, mild cardiomegalie, atrial septal defect, OFC at 4.5m at 15. centile, head normocephaly, coarse hair, closed posterior fontanels, abnormal ears, clinodactyly of all four toes bilaterally
0X-
CW-
4		 female/
13y		 PBL n.a. 47,XX,+mar[40%]/
46,XX[60%]		 r(X)
marker varied in size from cell to cell and in some cells the mass that fluoresced was several times the size of the FISH site on a normal X.		 different FISH-probes:
all centromeric probes		 epilepsy with DD, MR {7} case 5
0X-
CW-
5		 female/
12.5y		 PBL n.a. 47,X,dup(X)(q?),+r[1]/
46,X,+r[7]/
46,X,dup(X)(q?)[55]
45,X[7]		 r(X) wcpX Turner syndrome {16}
0X-
CW-
6		 female/
8y		 PBL n.a. 47,X,der(X),+r[25%]/
46,X,der(X)[75%]		 r(X) cepX Turner syndrome {17}
0X-
CW-
7		 female/
n.a.		 PBL n.a. 47,XX,+mar[100%] r(X)(wcpX+) wcpX, cepX hypomelanosis of Ito having MR, DD, hypotonia and behavioral problems; DYS, short stature, dysgenesis corpus callosum {25}
0X-
CW-
8		 female/
1y		 PBL/
buccal mucosa		 n.a. 47,XX,+r[100%]
BM: mar in 40%		 r(X)(wcp+, cep+, XIST-) wcpX, cepX, XIST hypotonia, developmental delay, brachycephaly, asymmetric white matter volume loss on brain MRI; {26}
0X-
CW-
9		 n.a./
postnatal		 PBL maternal 47,+r[?%]/
46[?%]		 r(X)(wcp+, cep+,XIST-) wcpX, cepX, XIST DD, psychomotor retardation, speech delay {32} case 6
0X-
CW-
10		 male/
prenatal		 AF and PBL de novo 47,XXY[?%]/
47,XY,+mar[?%]/
46,XY[?%]		 mar(X)(wcp+, cep+,XIST-) wcpX, cepX, XIST IUGR; postnatal growth retardation as well - but no mental problem after 36 months {34}
0X-
CW-
11		 male/
5y		 PBL de novo 47,XY,+mar[17/
46,XY[83]		 r(X)(cep+,XIST-) cepX, XIST born with normal weight and bilateral cryptorchidism; at 5 y suspicion of fragile X-syndrome due to MR, speech disorder, DD,  weight and height 50-75 percentile, OFC normal; {37}