(Acta Paediatr Jpn 1992; 34: 534

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538)

Case Reports

A Mosaic Case of Isodicentric Chromosome 18 Masataka Fujiwara, M.D., Ph.D., Hotaka Kamasaki M.D., Yasuyuki Morita M.D., Ph.0. and Makoto Kamada M.D., Ph.D. Department of Pediatrics, Hakodate Municipal Hospital, Hakodate, Hokkaido, Japan A case of mosaicism of isodicentric chromosome 18 is reported. Dicentric chromosome 18 occurs rarely and only five cases of isodicentric chromosome 18 have been documented. A high resolution banding method revealed that the karyotype of the patient was mos 46,XX/46,XX idic(l8Xpte1-q21.3::qt1.3-+pter), and the ratio of normal and abnormal

clones was 1:l. The clinical manifestations, resembling those of trisomy 18 syndrome, were affected by both partial trisomy 18pte1-qZ1.3 and partial monosomy 18q21.3-qter. Key Words Chromosome abnormalities, Human chromosome 18, Dicentric chromosome, Isochromosome, Mosaic

Introduction A rare case of isodicentric chromosome 18 with severe mental retardation and several malformations is reported. A high resolution banding method revealed the karyotype of the patient as mos 46,XX/46,XX,idic(18)(pter-.q21.3::q2 I . 3 "pter), and the mixture rate was 1:l. The clinical manifestations, which resemble those of the trisomy 18 syndrome, are described and compared with other previous cases.

Case Report The patient is a 6 year old female. She has been monitored for growth and developmental retarReceived January 13, 1992 Revised May 7, 1992 Accepted May 22, 1992 Correspondence address: Dr M. Fujiwara, Department of Pediatrics, Hakodate Municipal Hospital, Yayoi-cho 2-33, Hakodate, Hokkaido, Japan.

dation based on chromosomal aberration. She has suffered repeated respiratory and gastrointestinal infections that have necessitated several hospital admissions. The patient was born as the second child of her parents after a gestation period of 39 weeks with a weight of 2,350g. The pregnancy and delivery were not complicated. At the time of her birth, her father was 38 years old and her mother 35 years old. The parents and the then 10 year old sister of the patient were healthy and had no contributive anamnesis. There was no family history of malformations or chromosomal aberrations. She was admitted to hospital for feeding disturbance and severe growth retardation 6 months after birth. Chromosomal analysis with the G-banding method, which was performed at the time of the first admission, proved her chromosomal status to be that of a mosaic of trisomy 18q. Microcephalus with occipital prominence, microphthalmia, poorly developed and mal-

Mosaic isodicentric chromosome 18 (45) 535 formed ears, micrognathia, short lingual frenulum (‘tongue-tie’), high-arched palate, low posterior hairline, overlapping fingers, rockerbottom feet, bilateral simian creases and bushy eyebrows were described upon admission. These are common symptoms observed in cases of trisomy 18. Computerized tomography revealed no intracranial malformations. No cardiovascular, gastrointestinal or genital malformations could be found. X-ray films of the spine showed a mild scoliosis. Renal scintigraphy and renal computerized tomography revealed a horse-shoe kidney. Microhematuria has been observed constantly since she was 5 years old. Auditory evoked brain stem response (ABR) testing revealed perceptive hearing impairment, and the patient uses hearing aids. Severe mental and motor retardation have been observed since her early infantile period. Six months after birth, she did not smile with coaxing, and could not turn over or sit up by herself. She continues to be severely retarded, however she is slowly but surely developing. Currently she is attending a training institution. Motor development at present is relatively good; she cannot run, but she can walk well and climb up and down stairs while holding on to the handrails. Mental retardation is still severe, but she can understand some simple orders such as ‘bring it to me’ (Fig. 1). Chromosomal analysis with the high resolution banding method revealed a mosaic of isodicentric chromosome 18, and her karyotype was confirmed as mos 46,XX/46,XX,idic( 18)(pter-.q21.3::q21.3-+pter). The ratio of normal and abnormal clones of peripheral lymphocytes was 1:l (Fig. 2). Two centromeres were identified in the dicentric chromosome with the C-band method. Since one of them was inactive and dissociated, it was thought to be a pseudodicentric chromosome (Fig. 3).

Discussion Abnormalities of chromosome 18 appear relatively frequently. The trisomy 18 syndrome is the second most common autosomal aberration [1I. However, dicentric chromosome 18 is rare,

Vol. 34 No. 5 October 1992

Fig. 1: Whole body feature of the patient.

as is isochromosome 18. Some of the cases of dicentric chromosome, which occurs through a reciprocal translocation between chromosome 18 and other chromosomes, have been reported [2-91, but only four documented reports on isodicentric 18 are traceable 110-1 31. The kary-

536 (46) Fujiwara et al.

q22---

q21.2---

q12 .l---

pll.31-

Fig. 2: Partial karyotype of chromosome 18. The high resolution banding method revealed that 10 of 12 peripheral lymphocytes possess an isodicentric chromosome 18.

otypes of the previous five cases with isodicentric chromosome 18 as well as the present case are summarized in Table I. Table 2 shows their clinical manifestations as reported. The reporters of the first four cases

described them as having a close resemblance to complete trisomy 18 [lo-121. The reporter of case 5 suggested that the congenital anomalies of the case were most consistent with 18q - syndrome [ 131.

Acta Paediatr Jpn

Mosaic isodicentric chromosome 18 (47) 531 Table 1. Karyotypes of the cases of isodicentric chromosome 18. The frequency of the peripheral lymphocytes with the isodicentric chromosome 18 were 50% in case 4 and the present case, and 35% in case 5 No. of cases 1

2 3 4 5 6

Reference

Karyotypes

10 10 11 12 13 Present case

46,XY,idic( 18)(qter+pter::pter-.qter) 46,XX,idic(1I)(qter-pter::pter-+qter) 46,XY,idic( 18)(qter-+pll::pl l-qter) 46,XX/46,XX,idic(18)(pter-+q21.3::q21.3+pter) 46,XX/46,XX, - 18,dic(l8)(pter-q12.2::q12.2-pter) 46,XX/46,XX,idic(18)(pter-q21.3::q21.3-+pter)

When considering the clinical manifestations, the present case bears much resemblance to trisomy 18 syndrome. In addition to this, she has some manifestations (e.g. depressed midface, congenital hearing impairment and recurrent infections) that are frequently observed in monosomy 18q syndrome.

From the standpoint of chromosomal quantity, this case must be considered as a complex of partial trisomy 18pter-+q21.3 and partial monosomy 18q21.3-qter. The prognosis of trisomy 18 syndrome is generally poor, with most of the patients dying in early infancy, with the exception of some

Table 2. Comparison of the manifestations of the patient with isochromosome 18 No. of cases Gestational timing (weeks) Birthweight (g) Feeding disturbance Growth retardation Mental and motor retardation Microcephalus Occipital prominence Microphthalmia Hypertelorism

1

2

3

4

5

6

36 1,700 ?

term 2,800

40 2,620

40 2,860

36 2,520

39 2,350

+

+

?

+ +

?

? ? ?

+

+ +

+ ?

+ +

?

+

?

?

?

+

?

+

+

+ +

+ +

?

?

? ?

?

+

+ +

+ +

+ +

? ?

? ?

? ?

+ +

Micrognathia High-arched palate Cleft palate Short lingual frenulum

+

+

?

? ? ?

? ? ?

+ +

+

? ?

? ?

+ ?

+

Short neck Short sternum Narrow pelvis

+

+

+

? ?

? ?

? t

? ? ?

? ? ?

-

Overlapping fingers Camptodactylia Bilateral simian creases Phocomelia of the forearms

+

+

+

+

?

? ?

? ?

? ? ?

+

+

? ? -

Rocker-bottom feet Harrow foot Feet syndactyly

?

-

Bushy eyebrows Redundancy of skin

?

+

Malformed ears Microtia Diminished response to sound

t

-

? ? -

+

+

? ?

?

+ + + ? ? ?

? ?

?

-

+

-

t

?

? ? ?

? ?

? ?

? ?

+

CHD + + + + Esophageal atresia ? ? + Horse-shoe kidney + ? ? Omphatocele ? ? + ? ? + , present; - ,absent; ?, not known; CHD, congenital heart disease. Case 6 is the present case.

Vol. 34 No. 5 October 1992

-

+ + + +

+ -

+

-

+ -

+

-

+ -

538 (48) Fujiwura et al.

2.

3.

Fig. 3: Partial karyotype of the abnormal clone obtained from the C-banding method.

partial trisomies, such as 18q distal trisomy syndrome and 18q- trisomy syndrome. It is thought that in the reported case mosaicism contributes to the patient’s long-term survival.

Acknowledgements

7.

8.

9. 10.

The authors reported this case at the 42nd Annual Meeting of the Northern Japan Society of Pediatrics in Akita, Japan, in September 1990. The authors gratefully acknowledge the advice of Hiroshi Shiono, M.D., Professor of Legal Medicine, Shimane Medical College, Shimane, Japan, and Jun-ichi Azumi, Ph.D., Lecturer in Legal Medicine, Sapporo Medical College, Sapporo, Japan.

12.

References

13.

1. Hirschhorn K. Clinical abnormalities of the autosomes. In Vaughan VC 111, MacKay RJ Jr, Behrman RE eds: Nelson Textbook of Pediatrics.

11.

14th ed. Philadelphia, 1992, WB Saunders, p 282-287. Funderburk SJ, Sparkes RS, Klisak I. 18psyndrome resulting from 14qll8q ‘dicentric’ fusion translocation. Hum Genet 1977; 39: 243250. Daniel A, Perel ID, Clarke AJ et al. Familial dicentric translocation t( 13;18)(p13;pl1.2)ascertained by recurrent miscarriages. J Med Genet 1979; 16: 73-75. Lambert JC, Ferrari M, Bergondi C et al. 18qsyndrome resulting from a tdic( 14p;18q). Hum Genet 1979; 48: 61-66. Turleau C, Chavin-Colin F, Narbouton N et al. Trisomy I8q-. Trisomy mapping of chromosome 18 revisited. Clin Genet 1980; 18: 20-26. Uehara M, Kida M. A complex mosaic with tdic (13;I8)(pll;pll). +13p-, +18p-,r(13)etc. i n a male infant. I. Centromere inactivation and dissociation of dicentric chromosome. Jpn J Human Genet 1986; 31: 27-35. Uehara M, Kida M. A complex mosaic with tdic (13;18) (pll;pl1). + 13p, + 18p-, r(13) etc. in a male infant. 11. Centromere inactivation and dissociation of dicentric chromosome. Jpn J Human Genet 1986; 31: 27-35. Maserati E, Waibel F, Weber B et al. A 45, X male with a Yp/18 translocation. Hum Genet 1986; 74: 126-132. Howard PJ, Berry AC. Familial transmission on a non-Robertsonian translocation dicentric. Clin Genet 1986; 29: 246-250. Laurent C, Biemont MC, Philip T et al. Translocations termino-terminales de novo entre deux chromosomes 18. A propos de deux observations 46,XYJer rea( 18;18) (pter;pter). Ann Genet 1978; 21: 78-82 (in French). Fioretti G, Stabile M, Pagano L et al. A case of Edward’s syndrome with pseudodicentric isochromosome 18: 46,XY,i dic(l8)(pIl::pll). Ann Genet 1982; 25: 116-1 18. Floore C, Robertson A, Samuel I et al. A pseudoisochromosome 18q and an isodicentric chromosome 18. Clin Genet 1989; 35: 450-454. Bryke CR, Lindgren V, Fryburg JS et al. Novel isodicentric chromosome 18 in an abnormal infant with a mosaic karyotype [46,XY/46,XY, - 18,+dic(lS)(q12.2)] Am J Med Genet 1990; 36: 247-250.

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