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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.

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

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

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The aetiology of the cat eye syndrome reconsidered

Cat

TABLE la

eye

synidrome: patients with abnormal

karyotype
Case No
I
2

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

3
4
5

6
7
8

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

10
11

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

Authors

cases

Sex

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

in Sebestyen and M6hesl4

Gerald,22 Petersen23

tSame cases in Freedom and

tSame case in Noel et a!36

Same
Same

case in Thomas et a140

cases in Emanuel et al49

109
TABLE Ic Patients
translocation

with partial trisomy 13 owing to

Case No

Authors

Sex

I
2
3
4
5

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

F
F
M
M
F

TABLE 1d Patients with 13 ring chromosome

Case No

Authors

Sex

I
2
3
4
5
6
7
8
9

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

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

TABLE

lb

Cat exe

syndrome: patients with normal

karyotype
Case No
I
2
3
4
5

6
7
8
9

10
11

Authors

Sex

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

F
F

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,

'vIK

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Ginevra Guanti

110

TABLE 2 Clinicalfindings

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

(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
+ ++ ++ ++

+++

++

+ ++

+ +

+++ ++

++

++

+++

+ +

++

+ ++ ++
+

+++

+ +

+++

+ +

++

+
+

+ +

++

+ +

+ +

+ +

++ + ++

+ +

+ + ++

+ +

+ +

.+

+ +

+ + ++

+++

+ +

+ +

+ +

+
+ +

+ +
+

+ +

+ ++

+++

++ +

+ ++ +

+ +

+
+ + ++

+ +

+++
++ +

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

malformations (D).

FIG 1

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.

case

2, ocular coloboma (C), gemfital

There was no familial history of congenital malformations.

Genetic studies
Buccal smears

were negative for sex chromatin.

Cytogenetic investigation on peripheral blood showed

,I

_, . ~ ~ -

LIBRARY
MAY 0 5 1981

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The aetiology of the cat eye syndrome reconsidered

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

+ ++
+
+

++ +
+
+
++
+

++
++

++

(d)

1 2 3 4 5
+

++
++
+
+
+

++

++

+
+
+

++

++

++ +

++
++
+
++ +
+

+
++

++

+ + ++

+
++

+
+

+
++

++

++

++

+++

+ +

+ +

+
+

+
+

+ +

++++
+++ ++++
+
+ ++++
++ ++

+ +
+

+
+

+ ++ +
++
++

++

++++
++++

++

1 2 3 4 5 6 7 8 9

++

+
++

+ +

(c)

+
++

+
++
+
+ ++ ++ ++ +
++
+
+
++
+
++
+
+
++
+
++
+
+

1 2 3 4 5 6 7 8 9 10 11

+
+

+
+ ++
+
+
+

(b)

++
+

EiE

IEDERLE LABORATORIESa BIV.,

++++

+ +

++ +

++++

++ +

++

.0,1

-a

'r-polf
5W

C...

.0
..

0-

Zt;IL-k

S.o

II

\N-

\%.,.

, c ..

Ilk

0le

. ... '.

Ai.=;;40f.

4e

6,4%
-

.:-,%
M.

21

2 2

%..

omew

f. )

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

FIG

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

Downloaded from jmg.bmj.com on March 27, 2014 - Published by group.bmj.com

112

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

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

Ginevra Guanti
CYTOGENETICS OF CASES WITH ABNORMAL
KARYOTYPE

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 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.

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.

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113

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

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

Conmplete
13 trisomy

Distal
trisomy

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

30/30
13/30
22/28
7/30
7/30
8/30

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

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

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

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

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

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

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

(fig 4).

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

(bands q2.--q33).

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114

Ginevra Guanti

Ub

IN--

22

22

I S S~~~~I.
13

13

a.
A
13

COMPARISON BETWEEN CES AND TRISOMIES

OF PROXIMAL REGION OF LONG ARM
OF CHROMOSOME 13

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

ears,

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).

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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115

The aetiology of the cat eye syndrome reconsidered

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.

(
0.

>-

2
-

.E

E Eo

CES WITH NORMAL KARYOTYPE

o0
D

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-

O
I

-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

RINGS

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-

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

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

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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Ginevra Guanti

116

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.
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Requests for reprints to Dr G Guanti, Institute of

Genetics, University of Bari, Via Amendola 165/A,
Bari, Italy

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The aetiology of the cat eye

syndrome reconsidered.
G Guanti
J Med Genet 1981 18: 108-118

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