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- CHROMOSOME #18 -
ABNORMAL
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(18)mat | UPD(18)pat | UPD(18)mat or pat |
| 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 |
| 18- W- pter |
see 18-U-10 | |||||||
| 18- W- p11.22/ 1-1 °°°
|
male/ prenatal |
AF | n.a. | 47,XY+mar[15]/ 46,XY[5] |
min(18)(:p11.22→q11.1:)* aCGH: 9.83-14.92 MB |
aCGH | AMA, cerebral malformation; DYS | {160} case 18 |
|
***
18-W- p11.21/ 1-1 |
n.a./ postnatal |
PBL | n.a. | 47,+mar[68%]/ 46[34%] |
min(18)(:p11.21→q11.2:)* array: distal clone in 18p RP11-756J15 (13.17MB) distal clone in 18q RP11-639E23 (19.34MB) |
aCGH | DD, DYS | {91} case 11 {109} case 8 |
|
***
18-W- p11.21/ 1-2 °°°
|
male/ 2.5y |
PBL | de novo | 47,XY+mar[41]/ 46,XY[9] |
mar(18)(:p11.21→q11.2:) array: 12.60-19.51 MB (hg19) equals in hg18: 12.59-17.76 MB |
aCGH (Illumina) | speech delay, minor VSD, atopic eczema, anxiety | {0} provided by Dr. Marie Trková, Praha, Czech Republic |
| 18- W- p11.21/ 2-1 |
male/ 49y |
PBL | n.a. | 47,XY,+i(18p)[15] | idic(18)(:p11.21→q10:) | cenM; subcenM; MCB |
severe MR, thin skin, hypogonadism, brachydactyly, long face, high palate, bilateral hearing loss; left hemiplagia (CVA 1992); DD - walking at 3 years; birth at term - 2800g | {75} case 18-4 |
| 18- W- p11.21/ 3-1 °°°
|
male/ 30y |
PBL/ BM |
de novo | 47,XY,+r[13]/ 46,XY[42] |
r(18)(::p11.21→q10::)* | all cep
probes; pericentric YAC clones as detailed in {66} |
normal pregnancy and delivery; learning disabilities; multiple symptoms summarized as Klippel-Trenaunay syndrome | {66} |
| 18- W- p11.21/ 4-1 |
male/ 3y |
PBL |
de novo | 47,XY,+r[35%]/ 46,XY[65%] |
r(18)(::p11.21→q2.32::) | aCGH | see below | {194} case 13 |
| DD, VSD, AR, Bilateral SNHL, Facial dysmorphic features, Bilateral UDT, Speech delay, Malformed, Posteriorly rotated and low set ears, Simian crease, 5th toe clinodactyly, Umbilical hernia, Sacral mongolian spot, Right lower limb paresis, Joint contractures, Bilateral pachygyria | ||||||||
| 18- W- p11.1/ 1-1 |
see 18-U-23 | |||||||
| 18- O- p11.1/ 2-1 °°°
|
female/ 1m |
PBL | de novo | 47,XX,+mar[15] | min(18)(:p11.1→q11.2:) FISH: BAC in 17.43MB present |
cenM; subcenM; MCB |
child without visible clinical signs; hyperbilirubinemia; artrial septal defect; open ductus botalli | {75} case 18-2 |
| 18- O- p11.1/ 2-2 °°°
|
male/ 13y |
PBL | n.a. | 47,XY,+mar[90%]/ 46,XY[10%] |
min(18)(:p11.1→q11.2:) FISH: BAC in 17.43MB present array: 15.18-17.48 |
cenM; subcenM; midi; aCGH |
child with 'abnormal behavior' (aggression and auto aggression) and small genitals. At birth head circumference at 3rd-10th, and weight at 3rd centile. At 13y OFC at 75-90 centile and obesity | {158} case Sm-8 |
| 18- W- p11.1/ 2-3 °°°
|
female/ 11m |
PBL; fibroblasts | n.a. | 49,XX,+marx3[1]/
48,XX,+marx2[2]/ 47,XX,+mar[25]/ 46,XX[32] no sSMC in skin fibroblasts |
mar(18)(:p11.1→q11.2:) aCGH: size 3.4 MB |
aCGH, cep 18 | hydrops, renal impairment, talipes | {148} case 7 |
| 18- W- p11.1/ 3-1 |
see 18-Ud-1 | |||||||
| 18- W- p11.1/ 4-1 |
male/ 24y |
PBL | de novo | 47,XY,+mar[4]/ 46,XX[26] |
r(18)(::p11.1→q11.2: :p11.1→q11.2: :p11.1→q11.2::) array: 16.1-21.12MB |
subcenM aCGH; UPD-test |
see below | {125} |
| uncomplicated pregnancy of 37 weeks, weight at birth of 2670 grams with a single umbilical artery; in first week diagnosed: anal atresia, dysplastic lumbar and sacral vertebrae, penoscrotal hypospadia, cryptorchism on both sides, bifid scrotum, ureteral flow abnormality (dilatation of the higher urinary tract caused by vesico ureteral reflux, trabeculated bladder), radial dysplasia and thumb hypoplasia on the right upper extremity and preaxial polydactyly of the left hand. The diagnosis VACTERL-association was made, although there were no abnormalities of heart, trachea and esophagus. The urinary flow problems resulted in frequent infections and some episodes of urosepsis, finally causing chronic renal insufficiency. In his teens he underwent cholecystectomy because of an abnormal gallbladder full of stones. A pancreas fissum was seen. Neurologic investigation showed no signs of tethered cord syndrome. School performances were normal, there were no reasons for IQ testing. As an adult his height was on the 3rd centile and his headcircumference was normal. | ||||||||
| 18- W- p11.1/ 5-1 °°°
|
male/ 23y |
PBL | mat (10% sSMC instead of normal #18) |
47,XY,+mar[75]/ 46,XX[25] |
r(18)(::p11.1→q21::) | FISH with locusspec. probes | see below | {140} |
| birth weight
2,250 g (<3rd centile), length 42 cm
(<3rd centile). At 9 months hypotonia,
motor retardation, microcephaly,
(occipitofrontal circumference [OFC] 42 cm;
<3rd centile), hypotelorism, depressed
nasal bridge, underdeveloped alae nasi, very
hypoplastic columella, smooth philtrum,
deciduous single median maxillary central
incisor, bilateral clinodactyly,
cryptorchidism. length at the 10th centile
(68 cm), weight at the 50th centile (8.5
kg). At 3 years developmental quotient of 70
and IQ 44 with autistic features at age 6
years. At 9 years add. short stature at 125
cm (<3rd centile), normal weight (21.5
kg; 10th centile), and microcephaly (OFC 49
cm; <3rd centile). He had a permanent
single median maxillary central incisor,
long cupped ears with large lobes, and short
neck. Also small penis, cryptorchidism, flat
feet, frontotemporal atrophy, and large
cisterna magna, bifid pelvis on the left
kidney; at age 17 years severe sleep apnea.
At 23 years, he suffered from severe sleep
apnea, obesity, and idiopathic leg edema
treated with antidiuretics. Height 155
cm(<3rd centile) weight was 90 kg
(>97th centile), cognitively impaired,
but was well-mannered and very kooperative
with a friendly attitude. mother phenotypically normal except for a double ureter and bifid renal pelvis (as in son) |
||||||||
| 18- W- q12.2/ 1-1 |
n.a./ postnatal |
PBL | n.a. | 47, XN,+mar[100%] | idic(18)(q12.2) | aCGH | DD | {109} case 16 |
| case
no. |
gender/ age at diagnosis |
studied material |
de
novo/ Inherited |
GTG-banding and final FISH result | test methods |
clinical
symptoms |
Reference |
| 18- W- IMB- p11.32/ 1-1 °°°
|
male/ 11y |
PBL | n.a. | 46,XY,dup(18)(p11.21p11.32), inv(20)(p13q11) 10.2MB |
aCGH | mild MR, growth retardation, mild DYS, behavioural problems, hernial inguinalis, ADHD | {114} case 71 |
| 18- W- IMB- q11.2/ 1-1 °°°
|
n.a./ postnatal |
PBL | n.a. | 46,dup(18)(q11.2) | n.a. | knee dislocation and hyperpigmentation | {96} |
| 18- W- IMB- q11.2/ 1-2 °°°
|
n.a./ postnatal |
PBL | n.a. | 46,dup(18)(q11.2) | n.a. | knee dislocation and hyperpigmentation | {105} |
| 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 |
| 18- CW- 1 |
male/ 23y |
PBL | n.a. | 47,XY,+mar | r(18) | SKY | Klippel-Trenaunay-Weber syndrome | {14} case 6 |
| 18- CW- 2 |
see 18-Uc-1 | |||||||
| 18- CW- 3 |
male/ prenatal |
AF | de novo | 47,XY,+r[28%]/ 46,XY[72%] |
r(18) | FISH with all available centromeric probes | TOP; autopsy showed 2 vessels in umbilical cord; abnormal left kidney. | {12} case 10 |
| 18- CW- 4 |
female/ postnatal |
PBL | n.a. | 47,XX,+mar[mosaic status unclear] | dic(18) | primed in situ hybridization (PRINS) | DYS like brachycephaly, short upper jaw, missing ear-lobe, micrognathia | {16} |
| 18- CW- 5 |
female/ 1d |
fibroblasts | de novo | 47,XX,+mar[15%]/ 46,XX[85%] |
mar(18) | FISH with all available centromeric probes | Baby was delivered at term but died one day after birth; abnormal facial appearance, abnormal position of the limbs, ventricular septal defect, non-mmunological hydrops fetalis | {22} case 33 |
| 18- CW- 6 |
n.a./ n.a. |
n.a. | n.a. | 47,+mar[?%] | mar(18) | FISH with ? | developmental abnormal | {73} 1 case |
| 18- CW- 7 |
female/ 8m |
PBL | de novo | 47,XX,+mar[30%]/ 46,XX[70%] |
mar(18) | PRINS | see below | {73} case 3 |
| DD, weight at 5th centile, lenght at 10. centile, OFC at 5th centile at 8m. mild hypotonia, flat nasal bridge, high arched palate, protruding tongue, capillary hemangiomas on the left upper eyelid, lower lip, right side of the back, right upper chest, right second finger, and left fifth finger; patent ductus arteriosus. | ||||||||
| 18- CW- 8 |
male/ newborn |
PBL | de novo | 47,XY+del(18)(q11)[100%] mar looks like an i(18p!!) |
n.a. | no FISH | developmental abnormal | {92} |
| 18- CW- 9 |
male/ newborn |
PBL | de novo | 47,XY,+del(18)(q11)[100%] | n.a. | no FISH | developmental abnormal | {93} |
| 18- CW- 10 |
n.a./ prenatal |
AF | de novo | 47,+mar[17%]/ 46[83%] |
mar(18) | wcp18; cep18 | Abnormal triple test, sonographic malformations (facial dysmorphism), TOP; Fetopathology low set ears, retrognathism | {119} case 8 |
According to {32} i(18p) commonly form through meiosis II non-disjunction immediately followed by meiotic or early post-meiotic mitotic miss-division at the centromere; the i(18p) are preferentially of maternal origin. Exceptions are familial forms like described in {35, 37, 39, 43}.
Here some guidelines how to deal best with tretasomy 18 patients from "The Chromosome 18 Registry & Research Society"