Journal ofMedical Genetics, 1981, 18, 108-118

The aetiology of the cat eye syndromereconsideredGINEVRA 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 andphysical retardation. An analysis of published reports revealed that of the 57 reported cases, only 21showed 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 livingsubjects of trisomy 22 arising from an inherited Robertsonian translocation; (2) the recurrentabortions in carriers of Robertsonian translocations involving chromosome 22; and (3) the existenceof 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, 13rings, 13 deletions, and CES the small marker present in this syndrome is considered to be a chromo-some 13 with an interstitial deletion.An attempt to map this chromosome has been made.

One century ago, Haab' described the clinicalassociation of ocular coloboma and anal atresia. In1965 Schachenmann et al2 were the first to find asupernumerary acrocentric chromosome in threesubjects with these malformations.The term 'cat eye', derived from the particular

appearance that the vertical iridochoroidal colobomagives to these patients, was introduced by Geraldet al.3The syndrome is usually ascribed to the presence

of a small submetacentric or acrocentric chromo-some, but there are several case reports in which nochromosomal abnormality is apparent.4-8

Although cytogenetic investigations have notprovided precise information, because of thesmall size of the supernumerary element, a22q - chromosome is believed to be involved. There-fore, the syndrome would depend on a partial22 trisomy.A recent examination of three patients with cat

eye syndrome (CES) and an accurate analysis of thepreviously reported cases2-49 (table 1 a, b, 2a, b)enabled us to make some observations about theclinical and cytogenetic picture of this syndrome.Received for publication 26 May 1980

Case reports

CASE 1

This was a newborn male infant, born after 40 weeks'gestation, the first child of a 30-year-old motherand 33-year-old father. The delivery was normal;birthweight 3000 g, head circumference 33 cm,length 55 cm. The following anomalies were ob-served: sloping forehead, prominent occiput, largefontanelles, widely patent cranial sutures, epicanthalfolds, hypertelorism, antimongoloid slanting eyes,depressed nasal bridge, prominent nose, increasedphiltrum length, malformed ears, bilateral preauric-ular skin tags and sinuses (fig 1A), high archedpalate, narrow chest, widely spaced nipples, andsmall scrotum with neither testicle palpable in thesac or in the inguinal canal. Anal atresia was notedat 48 hours after birth and was surgically resolvedon the third day. The baby showed failure to thriveand was admitted to hospital for salmonellosis andinfection of the urinary tract. He died 50 days afterbirth. Necropsy showed the following additionalabnormalities: micropolygyria of the frontal lobes,intestinal malrotation (fig 1B), megacolon, megaur-eter on right side, and abdominal testes. The death of

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TABLE la

karyotypeCat eye synidrome: patients with abnormal

Case No Authors Sex

I Ballesta et al9 Case 22 Case 33 Bass et al104 Beyer et all15 Bofinger and Soukupl26 *Buhler et al03 Case II1.I

Case 11.378 Cervenka et a1159 Cory and Jamison1610 Curciol711 Darby and Hughes'812 De Chieri et a!1913 Fryns et a12014 tGerald et al3 Case 115 Case 216 Case 317 Ginsberg et a12418 Giraud et a!2519 Gustavson et a126 Case I

20 Case 221 Hirschhorn et a!2722 Iselius and Faxelius2823 Ishmael and Laurence2924 Johnson et a13025 Krmpotik et al3l26 Kriger et a13227 Kunze et al3328 $Nishi et al3429 Noel and Quack,35 Noel et a13630 Petit3731 Pfeiffer et a13832 §Pierson et al3933 Punnett et a!4l34 Schachenmann et a12 Case 135 Case 236 Case 337 Schmid42 Case 138 Taft et a!4339 Taillemite et al4440 Toomey et al4541 Weber et a14642 Weleber et al4743 Zackai et a148 Case 144 Case 245 Zellweger et al4 Case 146 Our case 1

*Same cases in Sebestyen and M6hesl4tSame cases in Freedom and Gerald,22 Petersen23tSame case in Noel et a!36§Same case in Thomas et a140Same cases in Emanuel et al49

MFFMFFMMFFFFMMMMFFFFFFFMFFFFFMFFMMFFFFMFMFFFMFM

TABLE lb Cat exe syndrome: patients with normalkaryotypeCase No Authors Sex

I Franklin and Parslow5 Case I F2 Case 2 F3 James et a!6 Case 24 Case 55 Case 86 Case 157 Neu et al7 F8 Temtamy and McKusicks F9 Zellweger et a!4 Case 2 F10 Our case 2 M11 Our case 3 M

TABLE Ic Patients with partial trisomy 13 owing totranslocation

Case No Authors Sex

I Crandall et a150 F2 Giraud et a!51 F3 Jacobsen et a152 53 M4 Stoll et a!54 M5 Wilson and Melnyk55 F

TABLE 1d Patients with 13 ring chromosome

Case No Authors Sex

I Ailderdice et a156 Case 2 M2 Biles et a!57 M3 Grace et a158 Case 2 F4 Kistenmacher and Punnett59 Case 2 F5 Lejeune et a!60 Case 2 M6 Reisman et a161 M7 Rethor6 et a162 F8 Sparkes et a163 M9 Tolksdorf et a164 M

the patient was attributed to diffuse infection of theurinary tract and to salmonella septicaemia.The family history was unremarkable, with the

exception of a maternal cousin who died a few daysafter birth of biliary atresia. Both the parents werein good health and the mother had bilateral pre-auricular pits.

Genetic stiudiesSex chromatin was negative. Cytogenetic studies onperipheral blood showed a modal number of 47chromosomes with one extra chromosome smallerthan a G chromosome. It appeared to have satelliteson one end and to participate in satellite association.The identification of this supernumerary chromo-some was impossible even using G, Q, and C band-ing (fig 2). Blood and serum groups were normal.The karyotype of both parents was normal.

CASE 2

The patient was the first child of healthy unrelatedparents. At the birth the father was 28 years old andthe mother 21 years old. Delivery was normal; birthweight 3100 g, length 54 cm, head circumference31-9 cm. During the first weeks the baby sufferedfrom respiratory distress, cyanosis, constant feedingproblems, and failure to gain weight. Multiple con-genital malformations were noted including slopingforehead, facial asymmetry, antimongoloid slantingof eyes, bilateral coloboma of iris and choroid(fig 1C), right palpebral ptosis, prominent nose,macrostomia, micrognathia, low set ears, hyper-telorism, short neck with low posterior hairline,

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(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 retardationGenital malforniationsUrinary tract anomaliesKidney malformationsCardiovascular anomaliesFoot malformationsHand malformationsOther skeletal anomaliesLimited hip abductionVertebral malformationsPreauricular pits/tags/sinusesLow set malformed earsCleft lip or palateMicrognathiaMicrocephalyPtosisDownward slanting eyesEpicanthusStrabismusHypertelorismMicrophthalmiaColobomaAnal atresia or stenosis

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FIG 1 Case 1, ear malformations (A), intestinal malrotation (B); case 2, ocular coloboma (C), gemfitalmalformations (D).

widely spaced nipples, umbilical hernia, right There was no familial history of congenital mal-cryptorchidism, incurved penis (fig ID), and hypo- formations.spadias. Anal stenosis was suspected because ofpersistent constipation and thread-like stools. Renal Genetic studiesmalformations were suspected because of the per- Buccal smears were negative for sex chromatin.sistent high azotaemia. Cytogenetic investigation on peripheral blood showed

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TABLE 2 Clinicalfindings

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LIBRARY

MAY 0 5 1981EiE

IEDERLE LABORATORIESa BIV.,_, . ~~~~~--- I33 34 35 36 37 38 39 40 41 42 43 44 45 46

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

a modal number of 46 chromosomes. G, C, and Qbanding techniques did not reveal any structuralanomalies. Normal karyotypes were found in bloodcultures of both parents.

CASE 3

This was a newborn male infant born after 42 weeks'gestation by caesarian section. He was the first childof 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 followingmalformations: sloping forehead, hypertelorism,downward slanting eyes, epicanthal folds, bilateraliris coloboma, flattened nose, elongated philtrum,preauricular tags, radial dysplasia, vertebral mal-formations, ventricular septal defect, single umbilicalartery, low set ears, narrow chest, small scrotum,and bilateral cryptorchidism. Anorectal atresia wasnoted 24 hours after birth and was immediatelyresolved surgically. Two days after birth the patient

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112

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

Genetic studiesThe sex chromatin was negative. Chromosomeanalysis performed on peripheral blood cells of thepatient and his parents revealed normal karyotypes.

Discussion

CLINICAL SPECTRUMThe clinical spectrum of this anomaly is fairly wideas shown by several cases in which the extra chromo-some was transmitted directly from a phenotypicallynormal parent to a son with the cat eye syn-drome.2 317 18 31 The typical malformations includeanal atresia, usually associated with a rectoperinealor rectovaginal fistula, ocular coloboma, downwardslanting eyes, microphthalmia, hypertelorism, strab-ismus, epicanthus, preauricular tags, sinuses orfistulas, congenital heart defects, particularly septaldefects, urinary tract abnormalities, skeletal anomal-ies, and, frequently, mental and physical retardation.

DIAGNOSTIC CRITERIAInitially, the combination of coloboma and analatresia was the essential requisite for the diagnosisof CES. Subsequently the criteria became less re-strictive, and thereafter several cases of the incom-plete syndrome were reported.According to Hsu and Hirschhorn85 the diagnosis

of cat eye syndrome (CES) should be made accordingto the following minimal clinical criteria:

(1) a combination of the two major features, namelycoloboma and anal atresia, with or without otherassociated abnormalities;

(2) a combination of one major feature, colobomaor anal atresia, plus at least one of the mostfrequent associated specific anomalies, forexample, preauricular skin tags or sinuses orrenal anomalies;

(3) a combination of one major feature plus twoless frequent features, such as antimongoloidslanting eyes, skeletal anomalies, congenitalheart disease, and other eye defects;

(4) a combination of five or more minor specificfeatures.

In the light of criteria 2 and 3 we have includedin tables 1 and 2 several cases of full trisomy 22described as trisomy 22 syndrome.10 15 27 28 44 48However, based on criterion 4, all the cases oftrisomy 22 syndrome could be included.

Ginevra Guanti

CYTOGENETICS OF CASES WITH ABNORMALKARYOTYPEOf 57 subjects with clinical features of CES, 46 hada karyotype with an extra small marker chromo-some 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 ofa partial deletion of chromosome 22, but the in-volvement of this chromosome has never been welldocumented.

OBSERVATIONS WHICH QUESTION THEEXISTENCE OF TRISOMY 22 IN LIVINGSUBJECTSThe following observations question the existence oftrisomy 22.

(1) Living subjects with 22 trisomy arising from aninherited Robertsonian translocation have neverbeen reported.

(2) The carriers of a Robertsonian translocation in-volving a chromosome 22, which is an extremelyrare event, 6672 frequently have recurrent abor-tions.

(3) A syndrome dependent on trisomy of the distalregion of the long arm of chromosome 1173 82 iScharacterised by the same features as trisomy22, namely craniofacial dysmorphia, broad nose,long philtrum, micrognathia, malformed low setears with preauricular pits or tags, cleft palate,cardiac malformations, etc.

OBSERVATIONS WHICH QUESTION THEEXISTENCE OF PARTIAL TRISOMY 22Doubts about the existence of partial trisomy 22 areunderlined by the following considerations.

(1) If the extra chromosome gives rise to partialtrisomy for a chromosome 22, the affected per-sons would be expected to have some clinicalfeatures similar to the recognised full trisomysyndrome carriers, who obviously should presentmore marked consequences of the genomealterations. Instead one finds a more severephenotypic picture in the cat eye syndrome thanin the trisomy 22 syndrome.

(2) If the CES is the phenotypic expression of partial22 trisomy, the affected patients should have ashorter chromosome 22 than normal. Insteadthere are subjects with an extra chromosome ofthe same length as a 22 who exhibit the cat eyesyndrome10 15 26-29 32 45 and subjects with asupernumerary deleted chromosome who havethe trisomy 22 syndrome.83 84

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TABLE 3 Compar-isoni of some features in full 13 trisomy*, in par-tial 13 tr-isomiest, and in cat eye syndrome

Conmplete Distal Proximal CES with CES without13 trisomy trisomy trisomy marker marker

Menital retardation 26/26 100 30/30 100 7/9 78 29/36 80 6/11 55Microcephaly 16/25 64 13/30 43 3/7 43 18/39 46 4/11 36Low set malformed ears 20/25 80 22/28 79 3/7 43 43/46 93 9/11 82Cleft lip or palate 30/40 75 7/30 23 2/9 22 12/46 26 3/11 27Hypertelorism 24/26 92 7/30 23 3/6 50 23/45 51 4/11 36Epicanthus 14/25 56 8/30 27 2/6 33 12/45 27 4/11 36Coloboma 17/37 46 3/30 10 1/9 11 26/46 57 11/11 100Microphthalmia 19/25 76 6/30 20 1/9 11 8/45 20 3/11 27Cardiovascular anomalies 19/26 73 5/27 19 2/8 25 25/46 54 6/11 55Genital malformations 21/32 66 8/27 30 2/9 22 7/44 16 3/11 27Kidney malformations 13/32 41 9/27 33 0/6 0 9/46 20 2/11 18Inguinal/umbilical hernia 10/25 40 9/27 33 1/9 11 2/46 4 1/11 9Haemangioma 15/21 71 18/30 60 1/8 12 0/46 0 0/11 0Polydactyly 19/25 76 19/30 63 0/9 0 0/46 0 0/11 0Simian crease 16/25 64 11/19 58 2/9 22 4/21 19 3/7 43Distal t triradius 14/20 70 4/12 33 4/8 50 5/21 24 0/7 0Anal atresia or stenosis 0/37 0 1/30 3 0/9 0 33/46 72 6/11 55Sex (F: M) 35: 29 18 : 12 4: 4 31: 15 5: 2Maternal age 31.6 26.2 26-5 30-3 27.0Paternal age 31.9 30.3 29.6 32-9 31-5Gestational age 39-0 39-7 39.8 40.0 41.0Birthweight (g) 2610 3263 2926 2917 2691

*Data from Warkany et 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, severalauthors25 2B29-32 have already suggested that theextra chromosome present in the CES may be a

deleted 13; in fact, many clinical and pathologicalfeatures usually associated with trisomy 13 are pre-

sent in the cat eye syndrome (table 3).Besides this, in some cases of CES25 the extra

chromosome shows a bright centromere, a cyto-genetic feature typical of chromosome 13.We analysed all the malformation syndromes

depending on numerical and structural aberrationsof chromosome 13 and, according to criteria 2 and3 of Hsu and Hirschhorn,65 we found striking simi-larities between the cat eye syndrome and theclinical pictures associated with some 13 ringchromosomes 56-64 and some partial 13 trisomies50-55occurring 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 syn-

drome whenever they give rise to a duplication of thesame regions present on the supernumerary chromo-some in this syndrome. In deriving such a smallextra chromosome from a 13, different portions of13 may be involved in the constitution of the marker.This may account for the variability of the syndromeand make the identification of the marker impossibleby banding (fig 3). Furthermore, since the marker

chromosome could derive from a translocation be-tween the long arm of a 13 and the short arm ofanother D or G chromosome, for example the 22,the presence of only some characteristics (fluorescentsatellites, centromere, etc) of chromosome 22 cannotconstitute sufficient criteria for the correct identifica-tion of the marker (fig 3c-e).

MAP OF CHROMOSOME 13The clinical findings characteristic of partial tri-somy of proximal and distal regions of chromosome13 (table 3) have been delineated by Niebuhr.87Recently attempts to map chromosome 13 on thebasis of clinical features have been carried out.5' 88 89

Obviously a perfect phenotype-karyotype correla-tion cannot be achieved, since the genetic materialcontained in a chromosomal band correspondsto several hundred genes. Furthermore the attemptto map a chromosome meets with several difficultiesas stressed by Schutten et al.89 Nevertheless, weshould attempt to localise the regions responsiblefor the cardinal signs of the CES and, at the sametime, compare some of the clinical features of thepartial 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 chromosomalrearrangement which most frequently gives rise tothe marker chromosome is an interstitial deletioninvolving the central region of the 13 long arm(bands q2.--q33).

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13

22

I S S~~~~I.

22

13

a.A

13

FIG 3 Schematic representation ofpossiblerearrangements ofchromosome 13. (a, b)Interstitial deletion which in b gives rise to achromosome showing the same bandingpattern as a 22. (c, d) 13/22 translocationgiving rise to a marker chromosome withcharacteristics (centromere and/or satellites)ofa 22. (e) Partial karyotype illustratinghow a rearranged 13 chromosome resemblesa 22 (G banding).

COMPARISON BETWEEN CES AND TRISOMIESOF PROXIMAL REGION OF LONG ARMOF CHROMOSOME 13Psychosomatic retardation, microcephaly, low setears, micrognathia, clinodactyly, microstomia, epi-canthus, cleft palate, abnormal dermatoglyphs,increased t triradius, which are frequently describedin trisomies of the proximal q region, are present inthe CES too. The ocular coloboma frequent in theCES has been found once in trisomies of the proxi-mal q region.52The lack ofcoloboma in the other eight cases88 9096

may be for the following reasons: (1) the trisomicregion does not include the coloboma locus which,according to our map (fig 4), may be in the q13region; (2) the trisomic region partially comprises

the q13 region, excluding the coloboma locus; and(3) the locus is included in the trisomic region, butis silent. The latter could be accepted, if we considerthat the coloboma is present in only about 50% ofcases of complete trisomy 13.The trisomy of the region slightly distal (ql4)

would determine cardiac, renal, and genital mal-formations, anomalies rare in trisomies of theproximal q region and more frequent in the CES.

COMPARISON BETWEEN CES AND TRISOMIESOF DISTAL REGION OF LONG ARM OFCHROMOSOME 13A comparison between partial trisomy of the distal qregion50 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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(

0.

° 2>-

- .EE Eoo0

D

O

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FIG 4 Schematic drawing ofchromwsome 13 map.

central region of the long arm (q2-+q33) which isnever 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, andbushyeyebrows, whichare frequentlyobserved in thesepartial 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.54Its absence in other cases51 88 96 97 may be attributedto the reasons mentioned above.

ANAL ATRESIA IN CES AND IN 13 RINGSAND DELETIONSThe anal atresia frequently present in CES, but never

described in complete or partial trisomies ofchromo-some 13, except the case reported by Giraud et al,51has been observed in seven56-58 61 63 64113 of 50 cases

of 13 rings and in three114-11 of 21 cases, 70% identi-

fled as chromosome 13,87 of 1 3q interstitial orterminal deletions.As stressed by McClintock,117 terminal deletions

are very rare events, since their formation, requiringthe loss of the telomere, determines an unstablecondition which can bring about elimination orfurther chromosomal change resulting from thefusion of chromatid ends.118 Therefore the idea thatthe anal atresia depends on a simple deficiency ofthe q terminal ends can be excluded.The presence of the same anomaly in monosomic

(rings and deletions) and trisomic (CES) conditionscould be explained by postulating the presence of a(regulatory?) site on the distal region q33 or q34which whenever involved in breakage may producesuch a dominant mutation.

CES WITH NORMAL KARYOTYPEA normal karyotype was found in 1 4-8 of 57 sub-jects with the CES (table lb, 2b). These cases sug-gest that there may be a non-chromosomal basis forthe syndrome, even in so called familial cases5 wherethe various features may be transmitted in an auto-somal fashion.

If we admit the existence of a non-chromosomalbasis, we can consider the association of CES withthe extra chromosome to be fortuitous whenever anaffected patient inherits the abnormal chromosomefrom a normal carrier parent.2 31718 31 Thishypothesis is not very convincing because, if in thelatter cases the normal phenotype depends on acondition of mosaicism, the mosaicism also foundin patients with CES remains unexplained.3 24 45Another possible explanation for the apparently

normal karyotype may be the existence of a chromo-somal aberration beyond the limits of our presenttechniques.However, the possibility which must also be con-

sidered is that we are dealing with two differentdisorders resembling each other clinically.

CES AND VATER ASSOCIATIONA similar combination of defects occurring in CESis present in VATER association (a non-randomcombination of congenital malformations consistingof vertebral defects, anal atresia, cardiac mal-formations, tracheo-oesophageal fistula, oesophagealatresia, radial and renal dysplasiall9 120) in such a waythat some overlapping of the two forms exists (ourcase 3).4-6 8

Most of the reported cases with the VATER assoc-iation are sporadic. However, gene mutations couldconceivably cause all these associated malformations.Several examples of dominant inheritance of someVATER traits are reported.121-123 It is of interest to

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note that in the history of several carriers of CES(our case 1)4 21 29 31 47 there is familial occurrence oftypical malformations.From these observations two questions arise. Is

there a correlation between CES and the familialoccurrence of any particular malformations? Doesthere exist a relation between CES and VATERassociation ?

In conclusion, from the cytogenetic point of view,we would like to postulate that the extra chromo-some present in CES is essentially constituted ofgenetic material belonging to chromosome 13.

Since banding techniques proved to be inefficientin identifying the abnormal chromosome, anotheruseful investigation would be to search for a genedosage effect or an abnormal inheritance pattern insome gene markers for the genes mapped on thesechromosomes. From the clinical point of view it isnecessary to explain whether the incomplete formsreflect a reduced expressivity or the existence of oneor more different entities.

References1 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. Lancet1965 ;ii:290.

3 Gerald PS, Davis C, Say BM, Wilkins JL. A novelchromosomal basis for imperforate anus (the cat's eyesyndrome) Pediatr Res 1968 ;2 :297.

" Zellweger H, Mikamo C, Abbo G. Two cases of multiplemalformations with an autosomal chromosomal aber-ration-partial trisomy D? Helv Paediatr Acta 1962;17:290-300.

5 Franklin RC, Parslow ML. The cat-eye syndrome, reviewand two further cases occurring in female siblings withnormal chromosomes. Acta Paediatr Scand 1972 ;61:581-6.

6 James PML, Karseras AG, Wybar KC. Systemicassociation of uveal coloboma. Br J Ophthalmol 1974 ;58:917-21.

7 Neu RL, Assemany SR, Gardner LI. Cat eye syndromewith normal chromosomes. Lancet 1970;i:949.

8 Temtamy SA, McKusick V. Absence deformities as partof 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. Sym-posium on "Karyotype phenotype", Pavia, 10-1ISeptember 1973. Bull Eur Soc Hum Genet 1973: 67-9.

1 Bass HN, Crandall BF, Sparkes RS. Probable trisomy 22identified by fluorescent and trypsin-Giemsa banding.Ann Genet (Paris) 1973;16:189-92.Beyer P, Ruch JV, Rumpler Y, Girard J. Observationd'un enfant debile mental et polymalforme dont lecaryotype montre la presence d'un petite extra chromo-some mediocentrique. Pediatrie 1968 ;23 :439-42.

12 Bofinger MK, Soukup SW. Cat eye syndrome: partialtrisomy 22 due to translocation in the mother. Am J DisChild 1977;131:893-7.

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of a child with Patau's syndrome. Ann Hum Genet 1975;38:305-7.

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Requests for reprints to Dr G Guanti, Institute ofGenetics, University of Bari, Via Amendola 165/A,Bari, Italy

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