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com

Journal of Medical Genetics, 1981, 18, 108-118

The aetiology of the cat reconsidered

eye

syndrome

GINEVRA GUANTI From the Institute of Genetics, University of Bari, Via Amendola 165/A, Bari, Italy
SUMMARY The cat eye syndrome (CES), usually ascribed to the presence of a deleted supernumerary 22 chromosome, is characterised by a typical clinical picture including anal atresia, ocular coloboma, preauricular tags or sinuses, congenital heart defects, urinary tracts anomalies, and mental and physical retardation. An analysis of published reports revealed that of the 57 reported cases, only 21 showed the complete form, and 11 had a normal karyotype. Several observations question the existence of a trisomy 22: (1) the absence of any report in living subjects of trisomy 22 arising from an inherited Robertsonian translocation; (2) the recurrent abortions in carriers of Robertsonian translocations involving chromosome 22; and (3) the existence of a syndrome, showing the same clinical features as trisomy 22, which is irrefutably dependent on a trisomy of the distal region of the 11 long arm. On the basis of a comparison of the clinical features in full trisomy 13, partial 13 trisomies, 13 rings, 13 deletions, and CES the small marker present in this syndrome is considered to be a chromosome 13 with an interstitial deletion. An attempt to map this chromosome has been made.

This was a newborn male infant, born after 40 weeks' gestation, the first child of a 30-year-old mother and 33-year-old father. The delivery was normal; birthweight 3000 g, head circumference 33 cm, length 55 cm. The following anomalies were observed: sloping forehead, prominent occiput, large et al.3 The syndrome is usually ascribed to the presence fontanelles, widely patent cranial sutures, epicanthal of a small submetacentric or acrocentric chromo- folds, hypertelorism, antimongoloid slanting eyes, some, but there are several case reports in which no depressed nasal bridge, prominent nose, increased philtrum length, malformed ears, bilateral preauricchromosomal abnormality is apparent.4-8 Although cytogenetic investigations have not ular skin tags and sinuses (fig 1A), high arched provided precise information, because of the palate, narrow chest, widely spaced nipples, and small size of the supernumerary element, a small scrotum with neither testicle palpable in the 22q - chromosome is believed to be involved. There- sac or in the inguinal canal. Anal atresia was noted fore, the syndrome would depend on a partial at 48 hours after birth and was surgically resolved on the third day. The baby showed failure to thrive 22 trisomy. A recent examination of three patients with cat and was admitted to hospital for salmonellosis and eye syndrome (CES) and an accurate analysis of the infection of the urinary tract. He died 50 days after previously reported cases2-49 (table 1 a, b, 2a, b) birth. Necropsy showed the following additional enabled us to make some observations about the abnormalities: micropolygyria of the frontal lobes, intestinal malrotation (fig 1B), megacolon, megaurclinical and cytogenetic picture of this syndrome. eter on right side, and abdominal testes. The death of Received for publication 26 May 1980 108

One century ago, Haab' described the clinical association of ocular coloboma and anal atresia. In 1965 Schachenmann et al2 were the first to find a supernumerary acrocentric chromosome in three subjects with these malformations. The term 'cat eye', derived from the particular appearance that the vertical iridochoroidal coloboma gives to these patients, was introduced by Gerald

Case reports
CASE 1

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The aetiology of the cat eye syndrome reconsidered

TABLE la

109
TABLE Ic Patients translocation
Case No
I 2 3 4 5

Cat

eye

synidrome: patients with abnormal

Sex

with partial trisomy 13 owing to

Sex
F F M M F

karyotype
Case No
I 2
3 4 5

Authors
Ballesta et al9 Case 2 Case 3 Bass et al10 Beyer et all1 Bofinger and Soukupl2 *Buhler et al03 Case II1.I Case 11.3

Authors

6 7 8
9
10
11

Cervenka et a115 Cory and Jamison16

Curciol7 Darby and Hughes'8 De Chieri et a!19 Fryns et a120 tGerald et al3 Case 1 Case 2 Case 3 Ginsberg et a124 Giraud et a!25 Gustavson et a126 Case I Case 2 Hirschhorn et a!27 Iselius and Faxelius28 Ishmael and Laurence29 Johnson et a130 Krmpotik et al3l Kriger et a132 Kunze et al33 $Nishi et al34 Noel and Quack,35 Noel et a136 Petit37 Pfeiffer et a138 Pierson et al39 Punnett et a!4l Schachenmann et a12 Case 1 Case 2 Case 3 Schmid42 Case 1 Taft et a!43 Taillemite et al44 Toomey et al45 Weber et a146 Weleber et al47 Zackai et a148 Case 1 Case 2 Zellweger et al4 Case 1 Our case 1
cases

12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
34

35 36
37

38 39 40 41 42 43
44 45

46
*Same

M F F M F F M M F F F F M M M M F F F F F F F M F F F F F M F F M M F F F F M F M F F F M F M

Crandall et a150 Giraud et a!51 Jacobsen et a152 53 Stoll et a!54 Wilson and Melnyk55

TABLE 1d Patients with 13 ring chromosome

Case No
I 2 3 4 5 6 7 8 9

Authors
Ailderdice et a156 Case 2 Biles et a!57 Grace et a158 Case 2 Kistenmacher and Punnett59 Case 2 Lejeune et a!60 Case 2 Reisman et a161 Rethor6 et a162 Sparkes et a163 Tolksdorf et a164

Sex
M M F F M M F M M

the patient was attributed to diffuse infection of the urinary tract and to salmonella septicaemia. The family history was unremarkable, with the exception of a maternal cousin who died a few days after birth of biliary atresia. Both the parents were in good health and the mother had bilateral preauricular pits.
Genetic stiudies Sex chromatin was negative. Cytogenetic studies on peripheral blood showed a modal number of 47 chromosomes with one extra chromosome smaller than a G chromosome. It appeared to have satellites on one end and to participate in satellite association. The identification of this supernumerary chromosome was impossible even using G, Q, and C banding (fig 2). Blood and serum groups were normal. The karyotype of both parents was normal.
CASE 2

tSame cases in Freedom and tSame case in Noel et a!36

in Sebestyen and M6hesl4 Gerald,22 Petersen23

Same
Same

case in Thomas et a140 cases in Emanuel et al49

TABLE

lb

Cat exe

syndrome: patients with normal

Sex
F F

karyotype
Case No
I 2 3 4 5

Authors Franklin and Parslow5 Case I Case 2 James et a!6 Case 2 Case 5 Case 8 Case 15 Neu et al7 Temtamy and McKusicks Zellweger et a!4 Case 2 Our case 2 Our case 3

6
7 8 9

10 11

F F F M M

The patient was the first child of healthy unrelated parents. At the birth the father was 28 years old and the mother 21 years old. Delivery was normal; birth weight 3100 g, length 54 cm, head circumference 31-9 cm. During the first weeks the baby suffered from respiratory distress, cyanosis, constant feeding problems, and failure to gain weight. Multiple congenital malformations were noted including sloping forehead, facial asymmetry, antimongoloid slanting of eyes, bilateral coloboma of iris and choroid (fig 1C), right palpebral ptosis, prominent nose, macrostomia, micrognathia, low set ears, hypertelorism, short neck with low posterior hairline,

110

TABLE 2 Clinicalfindings
(a) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32
+ ++ ++ ++ + + +

Psychosomatic retardation

Genital malforniations Urinary tract anomalies Kidney malformations Cardiovascular anomalies Foot malformations Hand malformations Other skeletal anomalies Limited hip abduction Vertebral malformations Preauricular pits/tags/sinuses Low set malformed ears Cleft lip or palate Micrognathia Microcephaly Ptosis Downward slanting eyes Epicanthus Strabismus Hypertelorism Microphthalmia Coloboma Anal atresia or stenosis

'vIK

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Ginevra Guanti

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FIG 1

Case 1, ear malformations (A), intestinal malrotation (B); malformations (D).

case

2, ocular coloboma (C), gemfital

widely spaced nipples, umbilical hernia, right cryptorchidism, incurved penis (fig ID), and hypospadias. Anal stenosis was suspected because of persistent constipation and thread-like stools. Renal malformations were suspected because of the persistent high azotaemia.

There was no familial history of congenital malformations.

Genetic studies Buccal smears

were negative for sex chromatin. Cytogenetic investigation on peripheral blood showed

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,I

LIBRARY MAY 0 5 1981

EiE

The aetiology of the cat eye syndrome reconsidered

(b)
(c)

IEDERLE LABORATORIESa BIV.,

(d)
+ ++ ++
1 2 3 4 5 +
1 2 3 4 5 6 7 8 9

33 34 35 36 37 38 39 40 41 42 43 44 45 46

1 2 3 4 5 6 7 8 9 10 11 ++

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2 Giemsa stained metaphase. (A) The arrow indicates the supernumerary chromosome; (B) Group G, Y and marker chromosomes from two G banded mitoses.

modal number of 46 chromosomes. G, C, and Q banding techniques did not reveal any structural anomalies. Normal karyotypes were found in blood cultures of both parents.
CASE 3

This was a newborn male infant born after 42 weeks' gestation by caesarian section. He was the first child of a 26-year-old mother and 35-year-old father. Birthweight was 3250 g, head circumference was

34 cm, and length was 50 cm. He had the following malformations: sloping forehead, hypertelorism, downward slanting eyes, epicanthal folds, bilateral iris coloboma, flattened nose, elongated philtrum, preauricular tags, radial dysplasia, vertebral malformations, ventricular septal defect, single umbilical artery, low set ears, narrow chest, small scrotum, and bilateral cryptorchidism. Anorectal atresia was noted 24 hours after birth and was immediately resolved surgically. Two days after birth the patient

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112

Ginevra Guanti
CYTOGENETICS OF CASES WITH ABNORMAL KARYOTYPE

developed respiratory distress and died on the third day. Unfortunately no pictures were taken. The family history was unremarkable.

Genetic studies The sex chromatin was negative. Chromosome analysis performed on peripheral blood cells of the patient and his parents revealed normal karyotypes.
Discussion
CLINICAL SPECTRUM

Of 57 subjects with clinical features of CES, 46 had a karyotype with an extra small marker chromosome of variable morphology and of variable length, that is, similar to or shorter than a 22. As previously mentioned, the simplest explanation for the origin of the abnormal chromosome is that of a partial deletion of chromosome 22, but the involvement of this chromosome has never been well documented.
OBSERVATIONS WHICH QUESTION THE EXISTENCE OF TRISOMY 22 IN LIVING SUBJECTS

The clinical spectrum of this anomaly is fairly wide as shown by several cases in which the extra chromosome was transmitted directly from a phenotypically normal parent to a son with the cat eye syndrome.2 317 18 31 The typical malformations include anal atresia, usually associated with a rectoperineal or rectovaginal fistula, ocular coloboma, downward slanting eyes, microphthalmia, hypertelorism, strabismus, epicanthus, preauricular tags, sinuses or fistulas, congenital heart defects, particularly septal defects, urinary tract abnormalities, skeletal anomalies, and, frequently, mental and physical retardation.
DIAGNOSTIC CRITERIA

Initially, the combination of coloboma and anal atresia was the essential requisite for the diagnosis of CES. Subsequently the criteria became less restrictive, and thereafter several cases of the incomplete syndrome were reported. According to Hsu and Hirschhorn85 the diagnosis of cat eye syndrome (CES) should be made according OBSERVATIONS WHICH QUESTION THE to the following minimal clinical criteria: EXISTENCE OF PARTIAL TRISOMY 22 (1) a combination of the two major features, namely Doubts about the existence of partial trisomy 22 are coloboma and anal atresia, with or without other underlined by the following considerations. associated abnormalities; chromosome gives rise to partial (2) a combination of one major feature, coloboma (1) If the extra chromosome 22, the affected perfor a trisomy or anal atresia, plus at least one of the most be would expected to have some clinical sons for frequent associated specific anomalies, to the recognised full trisomy similar features example, preauricular skin tags or sinuses or who obviously should present carriers, syndrome renal anomalies; of the genome marked consequences more (3) a combination of one major feature plus two one finds a more severe Instead alterations. less frequent features, such as antimongoloid phenotypic picture in the cat eye syndrome than slanting eyes, skeletal anomalies, congenital in the trisomy 22 syndrome. heart disease, and other eye defects; If the CES is the phenotypic expression of partial (2) (4) a combination of five or more minor specific 22 trisomy, the affected patients should have a features. shorter chromosome 22 than normal. Instead there are subjects with an extra chromosome of In the light of criteria 2 and 3 we have included the same length as a 22 who exhibit the cat eye in tables 1 and 2 several cases of full trisomy 22 syndrome10 15 26-29 32 45 and subjects with a described as trisomy 22 syndrome.10 15 27 28 44 48 supernumerary deleted chromosome who have However, based on criterion 4, all the cases of the trisomy 22 syndrome.83 84 trisomy 22 syndrome could be included.

The following observations question the existence of trisomy 22. (1) Living subjects with 22 trisomy arising from an inherited Robertsonian translocation have never been reported. (2) The carriers of a Robertsonian translocation involving a chromosome 22, which is an extremely rare event, 6672 frequently have recurrent abortions. (3) A syndrome dependent on trisomy of the distal region of the long arm of chromosome 1173 82 iS characterised by the same features as trisomy 22, namely craniofacial dysmorphia, broad nose, long philtrum, micrognathia, malformed low set ears with preauricular pits or tags, cleft palate, cardiac malformations, etc.

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The aetiology of the cat eye syndrome reconsidered

TABLE 3 Compar-isoni of some features in full 13 trisomy*, in par-tial 13 tr-isomiest, and in cat eye syndrome
Conmplete 13 trisomy
Distal trisomy
30/30 13/30 22/28 7/30 7/30 8/30
100 43 79 23 23 27 3/30 10 6/30 20 19 5/27 30 8/27 33 9/27 9/27 33 18/30 60 19/30 63 11/19 58 4/12 33 3 1/30 18 : 12 26.2 30.3 39-7 3263

113

Proximal trisomy
7/9 3/7 3/7 2/9 3/6 2/6 1/9 1/9 2/8 2/9 0/6 1/9 1/8 0/9 2/9 4/8 0/9 4: 26-5 29.6 39.8 2926

CES with marker

29/36 18/39 43/46 12/46 23/45 12/45 26/46 8/45 25/46 7/44 9/46
80 46 93 26 51 27 57 20 54 16 20 4 0 0 19 24 72 15

CES without marker

55 6/11 36 4/11 82 9/11 27 3/11 36 4/11 36 4/11 11/11 100 27 3/11 55 6/11 3/11 27 18 2/11 9 1/11 0 0/11 0 0/11 43 3/7 0 0/7 55 6/11 2 5: 27.0 31-5 41.0 2691

Menital retardation Microcephaly Low set malformed ears Cleft lip or palate Hypertelorism Epicanthus Coloboma Microphthalmia Cardiovascular anomalies Genital malformations Kidney malformations Inguinal/umbilical hernia Haemangioma Polydactyly Simian crease Distal t triradius Anal atresia or stenosis Sex (F: M) Maternal age Paternal age Gestational age Birthweight (g)
*Data from Warkany et

26/26 100 16/25 64 80 20/25 30/40 75 24/26 92 14/25 56 17/37 46 19/25 76 19/26 73 21/32 66 13/32 41 10/25 40 15/21 71 76 19/25 16/25 64 14/20 70 0 0/37 35: 29 31.6 31.9 39-0 2610

78 43 43 22 50 33 11 11 25 22 0 11 12 0 22 50 0 4

2/46
0/46 0/46 4/21 5/21 33/46 31: 30-3 32-9 40.0 2917

al15 and Taylor.86 tData from Niebuhr.87

COMPARISON BETWEEN THE CAT EYE SYNDROME AND THE FYNDROMES ASSOCIATED WITH TRISOMY OF CHROMOSOME 13

On the basis of the clinical features, several authors25 2B29-32 have already suggested that the extra chromosome present in the CES may be a deleted 13; in fact, many clinical and pathological features usually associated with trisomy 13 are present in the cat eye syndrome (table 3). Besides this, in some cases of CES25 the extra chromosome shows a bright centromere, a cytogenetic feature typical of chromosome 13. We analysed all the malformation syndromes depending on numerical and structural aberrations of chromosome 13 and, according to criteria 2 and 3 of Hsu and Hirschhorn,65 we found striking similarities between the cat eye syndrome and the clinical pictures associated with some 13 ring chromosomes 56-64 and some partial 13 trisomies50-55 occurring in unbalanced translocations (table ic, d, 2c, d). Obviously the 13 rings and the partial 13 trisomies show the same clinical picture as the cat eye syndrome whenever they give rise to a duplication of the same regions present on the supernumerary chromosome in this syndrome. In deriving such a small extra chromosome from a 13, different portions of 13 may be involved in the constitution of the marker. This may account for the variability of the syndrome and make the identification of the marker impossible by banding (fig 3). Furthermore, since the marker

chromosome could derive from a translocation between the long arm of a 13 and the short arm of another D or G chromosome, for example the 22, the presence of only some characteristics (fluorescent satellites, centromere, etc) of chromosome 22 cannot constitute sufficient criteria for the correct identification of the marker (fig 3c-e).
MAP OF CHROMOSOME

13

The clinical findings characteristic of partial trisomy of proximal and distal regions of chromosome 13 (table 3) have been delineated by Niebuhr.87 Recently attempts to map chromosome 13 on the basis of clinical features have been carried out.5' 88 89 Obviously a perfect phenotype-karyotype correlation cannot be achieved, since the genetic material contained in a chromosomal band corresponds to several hundred genes. Furthermore the attempt to map a chromosome meets with several difficulties as stressed by Schutten et al.89 Nevertheless, we should attempt to localise the regions responsible for the cardinal signs of the CES and, at the same time, compare some of the clinical features of the partial trisomies with the clinical picture of the CES For this comparison we must keep in mind that the proposed model (fig 3a, b) of chromosomal rearrangement which most frequently gives rise to the marker chromosome is an interstitial deletion involving the central region of the 13 long arm

(fig 4).

(bands q2.--q33).

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114

Ginevra Guanti

Ub

IN--

22

22

I S S~~~~I.
13

13

a. A
13

FIG 3 Schematic representation of possible rearrangements of chromosome 13. (a, b) Interstitial deletion which in b gives rise to a chromosome showing the same banding pattern as a 22. (c, d) 13/22 translocation giving rise to a marker chromosome with

characteristics (centromere and/or satellites) of a 22. (e) Partial karyotype illustrating how a rearranged 13 chromosome resembles a 22 (G banding).

COMPARISON BETWEEN CES AND TRISOMIES OF PROXIMAL REGION OF LONG ARM OF CHROMOSOME 13

ears,

Psychosomatic retardation, microcephaly, low set micrognathia, clinodactyly, microstomia, epicanthus, cleft palate, abnormal dermatoglyphs, increased t triradius, which are frequently described in trisomies of the proximal q region, are present in the CES too. The ocular coloboma frequent in the CES has been found once in trisomies of the proximal q region.52 The lack of coloboma in the other eight cases88 9096 may be for the following reasons: (1) the trisomic region does not include the coloboma locus which, according to our map (fig 4), may be in the q13 region; (2) the trisomic region partially comprises

the q13 region, excluding the coloboma locus; and (3) the locus is included in the trisomic region, but is silent. The latter could be accepted, if we consider that the coloboma is present in only about 50% of cases of complete trisomy 13. The trisomy of the region slightly distal (ql4) would determine cardiac, renal, and genital malformations, anomalies rare in trisomies of the proximal q region and more frequent in the CES.
COMPARISON BETWEEN CES AND TRISOMIES OF DISTAL REGION OF LONG ARM OF CHROMOSOME 13

A comparison between partial trisomy of the distal q region50 51 54 55 90 93 94-112 and CES is more difficult, since most of the cases of the former include the

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The aetiology of the cat eye syndrome reconsidered

115

(
0.

>-

.E

fled as chromosome 13,87 of 1 3q interstitial or terminal deletions. As stressed by McClintock,117 terminal deletions are very rare events, since their formation, requiring the loss of the telomere, determines an unstable condition which can bring about elimination or further chromosomal change resulting from the fusion of chromatid ends.118 Therefore the idea that the anal atresia depends on a simple deficiency of the q terminal ends can be excluded. The presence of the same anomaly in monosomic (rings and deletions) and trisomic (CES) conditions could be explained by postulating the presence of a (regulatory?) site on the distal region q33 or q34 which whenever involved in breakage may produce such a dominant mutation.
CES WITH NORMAL KARYOTYPE

E Eo
o0 D

O
I

A normal karyotype was found in 1 4-8 of 57 subjects with the CES (table lb, 2b). These cases suggest that there may be a non-chromosomal basis for the syndrome, even in so called familial cases5 where the various features may be transmitted in an auto-

-I4

FIG 4 Schematic drawing of chromwsome 13 map.

central region of the long arm (q2-+q33) which is never present in the small marker in the CES. This may account for the fact that polydactyly, syndactyly, and other hand and foot deformities, hernia, haemangioma, long incurved eyelashes, and bushy eyebrows, which are frequently observed in these partial trisomies, are almost alwaysabsent in the CES. Ocular coloboma is mentioned by Crandall et a150 (trisomy ql2-*qter), Wilson and Melnyk,55 and, unexpectedly, (trisomy q21-*qter) by Stoll et al.54 Its absence in other cases51 88 96 97 may be attributed to the reasons mentioned above.
ANAL ATRESIA IN CES AND IN AND DELETIONS
13

somal fashion. If we admit the existence of a non-chromosomal basis, we can consider the association of CES with the extra chromosome to be fortuitous whenever an affected patient inherits the abnormal chromosome from a normal carrier parent.2 31718 31 This hypothesis is not very convincing because, if in the latter cases the normal phenotype depends on a condition of mosaicism, the mosaicism also found in patients with CES remains unexplained.3 24 45 Another possible explanation for the apparently normal karyotype may be the existence of a chromosomal aberration beyond the limits of our present techniques. However, the possibility which must also be considered is that we are dealing with two different disorders resembling each other clinically.
CES AND VATER ASSOCIATION

RINGS

A similar combination of defects occurring in CES is present in VATER association (a non-random combination of congenital malformations consisting of vertebral defects, anal atresia, cardiac malformations, tracheo-oesophageal fistula, oesophageal atresia, radial and renal dysplasiall9 120) in such a way that some overlapping of the two forms exists (our
case 3).4-6 8

The anal atresia frequently present in CES, but never described in complete or partial trisomies of chromosome 13, except the case reported by Giraud et al,51 has been observed in seven56-58 61 63 64113 of 50 cases of 13 rings and in three114-11 of 21 cases, 70% identi-

Most of the reported cases with the VATER association are sporadic. However, gene mutations could conceivably cause all these associated malformations. Several examples of dominant inheritance of some VATER traits are reported.121-123 It is of interest to

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116

Ginevra Guanti
a family with trisomy 22 syndrome. Ophthalmologica

note that in the history of several carriers of CES (our case 1)4 21 29 31 47 there is familial occurrence of typical malformations. From these observations two questions arise. Is there a correlation between CES and the familial occurrence of any particular malformations? Does there exist a relation between CES and VATER association ? In conclusion, from the cytogenetic point of view, we would like to postulate that the extra chromosome present in CES is essentially constituted of genetic material belonging to chromosome 13. Since banding techniques proved to be inefficient in identifying the abnormal chromosome, another useful investigation would be to search for a gene dosage effect or an abnormal inheritance pattern in some gene markers for the genes mapped on these chromosomes. From the clinical point of view it is necessary to explain whether the incomplete forms reflect a reduced expressivity or the existence of one or more different entities.
References 1 Haab 0. Beitrage zu den angeborenen Fehlern des auges. Albrecht von Graefes. Arch Ophthalmol 1878;24:257-81. 2 Schachenmann G, Schmid W, Fraccaro M, et al. Chromosomes in coloboma and anal atresia. Lancet 1965 ;ii:290. 3 Gerald PS, Davis C, Say BM, Wilkins JL. A novel chromosomal basis for imperforate anus (the cat's eye syndrome) Pediatr Res 1968 ;2 :297. " Zellweger H, Mikamo C, Abbo G. Two cases of multiple malformations with an autosomal chromosomal aberration-partial trisomy D? Helv Paediatr Acta 1962;17: 290-300. 5 Franklin RC, Parslow ML. The cat-eye syndrome, review and two further cases occurring in female siblings with normal chromosomes. Acta Paediatr Scand 1972 ;61: 581-6. 6 James PML, Karseras AG, Wybar KC. Systemic association of uveal coloboma. Br J Ophthalmol 1974 ;58: 917-21. 7 Neu RL, Assemany SR, Gardner LI. Cat eye syndrome with normal chromosomes. Lancet 1970;i:949. 8 Temtamy SA, McKusick V. Absence deformities as part of syndromes. Birth Defects 1978;14, No 3:135-46. 9 Ballesta Martinez F, Repiso J, Altirriba 0, Villaz L. Three new cases of a small extra chromosome. Symposium on "Karyotype phenotype", Pavia, 10-1I September 1973. Bull Eur Soc Hum Genet 1973: 67-9. 1 Bass HN, Crandall BF, Sparkes RS. Probable trisomy 22 identified by fluorescent and trypsin-Giemsa banding. Ann Genet (Paris) 1973;16:189-92. Beyer P, Ruch JV, Rumpler Y, Girard J. Observation d'un enfant debile mental et polymalforme dont le caryotype montre la presence d'un petite extra chromosome mediocentrique. Pediatrie 1968 ;23 :439-42. 12 Bofinger MK, Soukup SW. Cat eye syndrome: partial trisomy 22 due to translocation in the mother. Am J Dis Child 1977;131:893-7. 13 Buhler EM, Mehes H, Muller H, Stalder GR. Cat-eye syndrome, a partial trisomy 22. Humangenetik 1972;15:
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The aetiology of the cat eye syndrome reconsidered.

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