a hereditary bisatellite-dicentric supernumerary chromosome

tieredilas 111: 7-10 (1989)

A hereditary bisatellite-dicentric supernumerary chromosome in a case of Cat-eye Syndrome GUVEN LULECI', GULSEREN BAGCI', MURUVET KIVRAN2, ERSIN L k E C I ' , SIKRI BEKTAS' and SEHER BA$ARAN3

' Departments of Medical Biology and Genetics, Radiology, Pediatrics, Medical Faculty, Akdeniz University, Antalya, Turkey Private Pediatrician, Turkey Institut fur Humangenetik, WWU, Munster, BRD

LULECI, G.. B A ~ C I . G., KIVRAN, M., LULECI, E., BEKTAS. S. and BASARAN. S. 1989. A hereditary bisatellite- dicentric supernumerary chromosome in a case of Cat-eye Syndrome. - Heredifus 111: 7-10. Lund, Sweden. ISSN 0018-0661. Received October 26, 1988. Accepted March 17, 1989

We studied the clinical and cytogenetic features of a case of Cat-eye Syndrome. The chromosomal analysis showed 47 chromosomes. The supernumerary small, metacentric. bisatellited marker chromosome was probably derived from a No. 22 and occurred as well in the proband's sister and mother.

Ciiven Luleci, Depurtmenr cf Medicul Biology and Genetics, Akdeniz universi~. Mediml Faculty, Antulya. Turkey

The Cat-eye Syndrome is a well-defined chromosomal syndrome first described by Schachenmann (SCHACHENMANN et al. 1965). Most of the patients had an extra, small, differently shaped chromosome (PETERSEN 1973; PIERSON et al. 1975; TOOMEY et al. 1977). The first report of a familial trisomy 22 p t e r j q l l with a Cat-eye Syndrome was reported in 1972 (BUHLER et al. 1972). It was suggested that most of the small metacentric or submetacentric extra chromosomes in the Cat-eye Syndrome were probably derived from a No. 22 (tetrasomy 22 pter+q11) (SCHINZEL et al. 1981). Recently, some scientists have supported this interpretation by in situ hybridization techniques (MCDERMID et al. 1986; DUNCAN et al. 1986, 1987). Here we report a case of Cat-eye Syndrome and the proband's normal family with the same extra chromosome.

Material and methods Case report: A female infant was born in hospital to healthy consanguineous parents after a term and uncomplicated pregnancy. The parents were first cousins. The mother was 32 and the father 3.5 years old. The perinatal history was unremarkable. The child was asphyctic after birth. Birth weight 3000 g, length SO cm, and head circumference 34 cm.

Physical examination revealed short neck and clavicle, flattened nasal bridge, microphthalmia, hy- pertelorism, bilateral coloboma of iris, epicanthus, strabismus, muscular hypotonia, shortness and hyperflexibility of upper and lower extremities, low- set abnormal ears, cleft palate and down slanted palpebral fissures. Abdominal ultrasound showed unilateral kidney, and CT revealed internal hydro- cephalus. At one year of age (Fig. l ) , her height was 74 cm (50th percentile), weight 8460 g (10-25 percentile), head circumference 5 1 cm (97 percentile).

Cytogenetical analysis

Peripheral blood leukocytes for the routine cytogenetical studies were cultured in Mc Coy's 5A sup- plemented with IS % fetal calf serum. The chromosomes were banded by Trypsin-Giemsa and CBG- banding techniques; NOR-staining was used to

et al. 1973; Howrii.~. and BLACK 1978). Show bisatellites (SEAHKIGIIT 197 I ; CRAlG-HOI.MRS

Results A cytogenetic analysis was carried out in this patient, referred to o u r laboratory because of an un-

tierediraq I I I (1989)

known syndrome. 100 cells were counted from the chromosome preparation of blood lymphocytes. All cells showed an extra, small, metacentric chromosome, approximately half the size of a normal G chromosome. The small chromosome was noted to have a bisatellite. The centromeric area was light and there were equal bands on the p and q arms as demonstrated by the GTG technique. The small chromosome bisatellites were mostly associated with other acrocentric chromosomes. CBG-banding showed that this marker chromosome was dicentric with centromeric areas of the same sizes.

Laboratory and clinical findings indicate that this marker chromosome is derived from a No. 22 (tetrasomy 22 pter-ql 1). Chromosomal preparations of peripheral blood lymphocytes from the mother and the sister of the proband show the supernumerary chromosome of same shape and size in all the 100 cells examined (Fig. 2).

The mother and the sister were phenotypically and mentally normal without an antimongoloid slant. The father's and maternal sister's karyotypes were normal. The maternal grandmother's karyotype was mosaic (8 %). The pedigree of this family is shown in Fig. 3.

I 2, I1 2, I1 6 may be mosaic carriers. I11 2 was said to have Cat-eye Syndrome with anal atresia, bilateral coloboma, antimongoloid slant, and other systemic anomalies. Apart from anal atresia, 111 3 had the same history but, additionally, an ear defor- mity. I1 5 and 111 22 were mentally retarded but we could not get any other detailed information. Fig. 1. Patient at age 1

BANDING TECHNIQUES

Hereditas I l l (1989) A CASE OF CAT-EYE SYNDROME 9

1 3 I I 1

11

III

I V

e,m Anal atresia

B,R Eye anomalies

@,Q Systemic anomalies @,@ Examined and normal

0,o Not examined normal

0,a Mentaly retarded 0, a Examined and mosaic @,a Chromosomaly abnormal in al l cells

b Abortion , Proband

by history

Fig. 3. Pedigree of the family.

Discussion Cat-bye Syndrome is characterized by coloboma, preauricular tags and/or pits, anal atresia, heart de- fects, and renal abnormalities. The combination of coloboma and anal atresia was the essential re- quisite for the diagnosis of Cat-eye Syndrome (complete syndrome). According to these diagnostic criteria, our case is incomplete (GUANTI 1981). The majority of Cat-eye Syndrome cases had an extra, small, metacentric, submetacentric, acrocentric or bisatellited chromosome (BOFINGER and SOUKUP 1977; VAN DYKE et al. 1977; SCHINZEL et al. 1981; WILSON et al. 1984). Recently, it has been demonstrated that this marker chromosome is a trisomy or tetrasomy of chromosome 22 pter-+qI 1 (BUHLER et al. 1972; SCIIINZEL et al. 1981; REISS et al. 1985; DUNCAN et al. 1986, 1987). Our chromosome analysis disclosed a normal karyotype and a supernumerary small, metacentric, apparently bisatellited marker chromosome in the proband, her sister, and her mother in all the 100 cells examined. The marker chromosome was observed to derive from a No. 22 (tetrasomy 22 pter+qI I ) . The homodicentric chromosome is formed during meiosis when there is breakage and re-union between two homologous ch rornosomes.

Although the typical Cat-eye Syndrome is associ-

ated with an extra chromosome, some cases with a normal karyotype have been reported (SAY 1970; FRANKLIN and FARSLOW 1972). A few authors have reported on familial Cat-eye Syndrome with an extra chromosome (SCHACHENMANN et al. 1965; BUH-

LER et al. 1972; PETERSEN 1973; WELEBER et al. 1977; SCHINZEL et al. 198 1 ; ING et al. 1987). In some of these families both parents were normal but grandparents and some relatives were either affect- ed or carriers (mosaic). Familial cases of Cat-eye Syndrome due to a balanced translocation in the parents, where No. 22 is involved, have also been identified (BOFINGER and SOUKLP 1977; KOSZTOLA-

N Y I and BUHLER 1985). In the present family, the proposita’s hydroce-

phaly and hyperflexibility of upper and lower extremities may be related to consanquinity. The mother and sister of the proband were phenotypically and mentally normal although they had the extra chromosome. The father’s and mother’s sister’s karyotypes were normal. Eight cells out of 100 cells of the maternal grandmother were mosaic, and the hi- stories of 111 2 and 111 3 indicate Cat-eye Syndrome. Therefore i t is probable that the grandmother’s father ( I 2) was also a mosaic and has transmitted the extra chromosome to at least two of his four child- ren ( I 1 2, I1 3).

However. it is difficult to understand how the proband can have a Cat-eye Syndrome while the mother and sister are normal. Probably. the grandmother had a submicroscopic interstitial deletion in one of the No. 22 chromosomes, possibly in the long arm. She must have transmitted the niarker chromosome and the deleted chromosome to her daughter 111 6. Thw. the mother’s normal child (IV 2) would have the same karyotype whereas the proband would have a couple of normal 22 and the marker chromosome.

Because of the chromosome morphology and clinical variance of the Cat-eye Syndrome we be- lieve that the previous papers should be re-evalua- ted. The techniques used in these studies. including the recent DADAPI technique, do not indicate fully the origin of the extra chromosome (ROStiNi.t:i-i> et al. 1984: VI:RMA et al. 1985: H o o 1986: PEREZ- CAmi 1.0 et al. 1987). In situ hybridization techniques wlith chromosome specific probes must be used in Cat-eye Syndrome patients when the site of chromosome involvement is not certain (DL:NCAN et al. 19x7). Thus. genetic counselling provided for familial cases phenotypically different but having a simi- lar marker chromosome will be more reliable.

References B o k i \ ( ; & K . 1.1. and SIX K L 1’. S . 1977. Cat-ebe Syndrnme. - A m

.I 0 1 s C h / d I I ’ / x93--x97

Cat-eye Syndrome a partial tnsonly 22. -- / l i m Gcwer I5 IS(b-167

C~~ ic ; -Ho i . rm . A. P.. Mo(.)RL. F. B. and Sii.4v.. M. W. 1972. Polymorphism of human C-band heterochromatin. 1. Frequency o f variants. ~~ Ant .I H i m ( ; c w ~ r . 25. 1x1-192

ur *.I( .\\, A. .M. \’.. HoL ( i H . c. A,. WHI 1’1 . B. N . and MCDCKMI~I.

H. E. 1086. R r i r i Communication: Breakpoint localization o f [he marker chromosome aswciated with the Cat-eye Syndromc.

Dr \<.&\. A. M. V. . Ros~\\.c.FI.I). W. and V C K V ~ . R. S. 1987. Letter 10 the Editor: Re-evaluation ot the wpernumerary chromoronie in the iiidi\,idual with Cat-eye Syndrome. - A m .I Mc’d. Gent / 27. 275--127

F K . \ \ K I I\, R. C . and FAK\I oh. hl. 1. IY72 The Catbeye Syndromr. Revieu and two further cases occurring in female sihlingc Hi th iiorm,4 chromomnes. -- 4 IU Pedrutr S M ~ 6/ 581-586

Gr \ \ i i . G. ISXI. The actlology o f the Cat-cye Syndrome reconci- derccl. -~ J .Wed Gem i . IN I O X - l I X

Bl 111 i R . E. M.. Mrt i rs, K . ML I.1.t-R. 13. and ST4l.Dt:R. G. R. 1972.

Am. .I /flint Gc,tiei 38 97X--98(1

genetics of C a t ~ e y Syndrome. ~ C/im Genet 29- 265-267 H o u ~ i I . W. M. and B L ~ U X . D. A. lY7X. A rapid technique for

producing s i l v e r d n e d nucleolus organirer regions and Tryp- \iii-Giemna bands on human chromosomes. - H u m Genet. 43: 5 3 56

W. G. and D i \ c a \ , A. M . V. 1987. Cat-eye Syndrome with different marker chromosomes in a mother and daughter. - Anr .I Med. Getret. 20 621428

Kosrrot .A\\ i , G. and Br FILER, E. M. I985 Partial trisomy 22- an old case reexamined. - Him Gener. 69: 193-194

I\<,, P. s.. LL H I \ S K Y . M. s.. SMITti. s. D.. GOI.DEN, E., SANGtR.

%fCI)E~R\lIU. H. E., DC’\CAN. A. M. V.. BRASCII. K., HOLDEN, J. I . . E. and WiirIt. B. N . 1986. Characterization of

the supernumerary chromosome in Cat-eye Syndrome. - s< I(” P 232 6 4 M 4 X

A. 19x7. Evidence for lack o f specificity of the D A D A P I technique. - C~~,qcrrrr Cell Getier. 45. 62

PFri RSI~\, R. A. 1972. Schmid-Fraccaro Syndrome (“Cat’s-eye Syndrome”). -- A t ( h . Ophtholmo/ YO: 187-291

dit De I‘Oeil de chat avec nanisme hypophysaire et develope- ment mental normal. -- Arrh. Fir Perficirr 32’ 832-848

Lwi+iE.\. E. W. and MA(;Lxis. R. E. 1985. Tandem duplication o f proximal 22 q: A cause o f Cat-eye Syndrome. - Ani J . Med. GCIW/ . 20: 165- 17 I

ROSE\I-~I .D. W.. VERMA. R. s. and JtiAVFRI, R. c. 1984. Cat-eye Syndrome with unusual marker chromosome probably not chromosome 22. -- Ani. J Mcd. Gcnrr . IN: 19-24

S A Y . B. 1970. Cat-eyc Syndrome with normal chromosomes. - L u m CI f2); 98

TIFKNO, L.. PFRo~A. C. P. and SARTORI, A. 1965. Chromo- somes i n coloboma and anal atresia. - Lcinwr ( 2 ) . 290

0 . . OI~ITL. J. M.. LISOS.I.ES. J., ZFTTRRQVIST, P., ENELL, H., B.ACCICHFITI, C., TE~ICOYI, R. and PA GO^. R. A. 1981. The Cat- eye Syndrome dicentnc small marker chromosome probably derived from a No. 22 (Tetrasomy 22 p ter - tq l l ) associated with a characteristic phenotype. - / h n Genet. 57: 148-158

S~ABRIGHI. M. 1971. A rapid banding technique for human chromosomes. - Lmic (’I (2 i . 97 1-972

TWVLY. K . E.. MOHAhUAS. T.. LtlsIi , J . , SCALAY, G. and KABACK, M. M. 1077. Further delineation of the supernumerary chromosome in the Cat-eye Syndrome. - Clin. Genet. I2: 275-284

V4\ D Y K ~ . D. L.. WFISS. L.. LIX~AN. M. and PAT, G. S . 1977. The origin and behaviour of two isodiccntric bisatellited chromosomes. ~~ A m . J . Hrmr Gewr 29. 294300

V C R V A . R. S.. BABI. K. A,, R o s t ~ k ~ t . ~ ) . W. and JHAVF.RI, R. C. 19x5. Marker chromosomes in Cat-eye Syndrome. - Clin. t i e - tl<’/ 27. 5 2 6 5 2 8

genetic invertigalion of Cat-eye Syndrome. - A m . .I. Ophrhul- nut/ HJ ’ 4 7 7 4 8 6

Wir s o \ , G. N.. BAKt-R. I). L.. SCIIALI, J . and PARKER. J. 1984. Cat- eve Svndrome owiny t o tetrasomy ?-? Dter-uI I. ~~ ./. M d

PFRL7-CASTII 1.0. A,. M.&Krih LUCAS. M. A. and ABRISOEUTA, J .

PlLRSO\. M.. Gii G F Y K K A \ T 7 . s. and SABORIO, M. 1975. Syndrome

Rriss. J. A.. WELLBLR. R. G.. BRVWh. M. G.. BAYGS. C. D..

~ C ! i . A C l i E ~ V A Y \ . G.. SCIIMIU, W.. FRACCARO. M.. MANNINI. A.,

%.HlSZEL. A,, ~ C H V I D . W.. FRACCARO. M., TWOLO. L.. ZLIFFARDI,

WF1.l.Ht.R. R. G.. WALKVOWSKI\. J . and PtAhblAN, D. 1977. CytO-

. . ~. H ~ X L J . I . 19x6. D A D A P I pattern 01 marlier chromostrmt.. Cyto- G c r r i c , r . 21: fib63

a hereditary bisatellite-dicentric supernumerary chromosome

Documents