J Med Genet: first published as 10.1136/jmg.14.4.288 on 1 August 1977. Downloaded from 288 Case reports 22 with 'cat eye' anomaly SUMMARY The case of a 10-month-old girl with an extra G-like chromosome is presented. Quinacrine, trypsin-Giemsa, and reverse banding identified the extra chromosome as no. 22. The phenotype of the patient is unique in that uni- lateral iris coloboma was observed, unlike the 18 cases of full trisomy 22 already published. This represents the first reported case of full trisomy 22 with this coloboma, or 'cat eye' anomaly, which is usually associated with partial trisomy 22. It is Al. suggested that the use of the term 'cat eye syn- drome' be revised. The terms 'partial trisomy 22 syndrome' and 'trisomy 22 syndrome' should be used instead.

Since Schachenmann et al. (1965) described the new chromosomal syndrome of trisomy of partially Fig. I Patient at 10 months ofage. Note the 'cat eye deleted , several reports of similar anomaly' and lack ofother malformations. cases have appeared (Buhler et al., 1972). In addition to mental retardation, the most prominent features distance of 2 35 cm was normal. Epicanthal folds were atresia ani and coloboma of the iris. Review of were as well as a mild degree of convergent the published reports indeed suggests that the iris present

strabismus. A pronounced iris coloboma of the rightcopyright. coloboma, or 'cat eye' anomaly, frequently has been eye was evident. Auricles were well-formed but present in cases characterised by the presence of a preauricular pits were observed bilaterally. The nasal supernumerary chromosome 22 which had bridge appeared depressed. Palate and mandible were of the distal portion of its long arms and not in cases not remarkable and examination of extremities, with full trisomy 22. We selected from the reports chest, and abdomen did not show any abnormality. 18 cases of full trisomy 22 in which identification of within the trisomic chromosome was reliably performed by Dermatoglyphs were the range of normal:

fingertip patterns consisted of 4 ulnar loops and http://jmg.bmj.com/ 6 banding techniques. All 18 patients with true trisomy whorls, the distal palmar triradius was positioned 22 lacked the 'cat eye' anomaly, a sign described in and flexion creases had normal most patients with the partial trisomy 22. proximally, palmar Heretofore, some authors applied the term 'cat configuration. eye syndrome' only to cases with partial trisomy 22, while complete trisomy of chromosome 22 was LABORATORY TESTS simply designated as 'trisomy 22 syndrome'. We Radiographic examination showed normal skull, are presenting a report of a patient with full trisomy chest, and skeletal maturation; the oesophagogram of chromosome 22 who had unilateral iris coloboma, was within normal limits. An EMI (computerized on September 27, 2021 by guest. Protected thus suggesting inconsistency of the above termi- tomogram of the skull) showed evidence of brain nology. atrophy, more prominent on the left, which mani- fested itself in enlargement of subarachnoid spaces in the frontal area and enlargement of the interhemi- Case report spheric fissure anteriorly. The electroencephalo- graphic evaluation was considered to be unremark- A 10-month-old Caucasian girl was referred for able. The blood tests showed normal levels of chlor- failure to thrive, muscle hypotonia, and coloboma of ide, sodium, potassium, calcium, phosphorus, and the right iris (Fig. 1). She was the first and only child magnesium. The urine was screened for mucopoly- of a 26-year-old mother and a 30-year-old father. saccharides, ferric chloride, nitroprusside, dinitro- Birthweight was 2583-5 g and birth length was 49 5 phenylhydrazine, and glucose oxidase, with negative cm. Examination disclosed a 43 0 cm head circum- results. Amino acid chromatography and serological ference and mild frontal bossing. The inner canthal analysis was also negative. J Med Genet: first published as 10.1136/jmg.14.4.288 on 1 August 1977. Downloaded from Case reports 289

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Fig. 2 G-banded karyotype ofthe patient with trisomy 22. copyright.

CYTOGENETICS chromosomes we have encountered an unusual Chromosomal study was made from peripheral finding. Among 190 mitoses examined, from blood lymphocytes by the modified micromethod of culture, 21 contained an unusual C-group chromo- Arakaki and Sparkes (1963) on two occasions. A some (Fig. 3) which was identified as number 10 by total of 77 mitoses were examined under the micro- G- and Q-banding. The distal portion of the long scope disclosing 47 chromosomes with an additional arms of this chromosome appeared deleted, but the G-group chromosome (Fig. 2). There was no indi- fragment was always present in the topographical http://jmg.bmj.com/ cation of mosaicism. To identify the supernumerary proximity of the long arms. This incidental obser- chromosome, G-, Q-, and R-banding techniques vation could not be related to the patient's (trisomy were employed. G-banded slides were prepared by 22) karyotype and it is being reported for the sake of trypsin treatment according to Seabright (1971); interest. In two cells, which did not contain this Q-banding by quinacrine dihydrochloride staining; abnormal C-group chromosome, trisomy of a G- and R-banding by the technique of Dutrillaux and group chromosome was identified. It was not obvious Lejeune (1971). Four G-banded karyotypes were whether this supernumerary chromosome was 21 or constructed, all showing the supernumerary chromo- on September 27, 2021 by guest. Protected some to be no. 22. No deletion was observed in the G-group or other chromosomes. This finding was a b c substantiated by R- and Q-banding. Further, both parents were analysed for chromosomal mosaicism since according to the review by Zellweger et al. Wi .-A (1975), in 4 of 37 families of 47,+22q- and 47,+22 ab. probands, parental mosaicism has been described. Chromosomal analysis of the patient's father and mother was performed on peripheral blood lym- Fig. 3 Chromosome IOfrom 11 % ofmother's mitoses phocytes. Of 50 mitoses counted in the father, 36 from peripheral lymphocytes showed incomplete deletion contained a normal diploid set ofchromosomes, none ofportion ofthe long arm. (a) Giemsa staining, (b) were hyperdiploid, and 14 had different hypodiploid G-banding, (c) BrdU-induced differential staining of numbers. However, in analysing the mother's sister chromatids. J Med Genet: first published as 10.1136/jmg.14.4.288 on 1 August 1977. Downloaded from 290 Case reports Table Review ofthe mainfeatures of18 cases of J. CERVENKA, CHERYL A. HANSEN, trisomy 22from the literature R. A. FRANCIOSI, AND R. J. Literature Present GORLIN case Division ofOralPathology, School of Dentistry, University ofMinnesota; and Children's Facial features Cleft palate 13/18 Health Center ofMinneapolis, Minneapolis, Preauricular skin tags and/or fistulae 11/18 + Minnesota, USA Microcephaly 11/18 - Micrognathia 11118 - Low-set ears 11/18 - Elongated philtrum 4/18 - References Iris coloboma ('cat eye') 0/18 + Arakaki, D. T., and Sparkes, R. S. (1963). Microtechnique for Other culturing leukocytes from whole blood. Cytogenetics, 2, Growth and mental retardation 17/18 + 57-60. Congenital heart anomalies 13/18 Hypotonia at birth or infancy 7/18 + Bass, H. N., Crandall, B. F., and Sparkes, R. S. (1973). Hip abnormalities 6/18 Probably trisomy 22 identified by fluorescent and trypsin- Failure to thrive 7/18 + Giemsa banding. Annales de GenOtique., 16, 189. Low-placed nipples 5/18 Buffoni, L., Reboa, E., Tarateta, A., Vianello, M. G., and Long, slender fingers and/or finger-like Banioli, E. (1974). Trisomy 22. Minerva Pediatrica, 26, thumbs 6/18 1895-1901. Inguinal hernia 4/18 Buhler, E. M., Meiles, K., Muller, and Stadler, R. (1972). Cat- eye syndrome, a partial trisomy 22. Humangenetik, 15, 150-162. Dutrillaux, B., and Lejeune, J. (1971). Sur un nouvelle tech- 22. From the cultured fibroblasts of the mother 75 nique d'analyse du caryotype humain. Comptes Rendus mitoses were analysed. Seventy-six per cent con- Hebdomadaires des S&snces de l'Acadgmie des Sciences, 272, 2630-2640. tained normal diploid numbers while 5 mitoses were German, J., Chaganti, R. S. K., Mirkinson, A. E., and hyperdiploid. Of these, 2 had 47 chromosomes with Morillo-Cucci, G. (1971). Trisomy 22. American Journal of supernumerary chromosome 22. Mitoses with un- Human Genetics 24, 56a. usual chromosomes were not detected. Hsu, L. H. R., Shapiro, L. R., Gertner, M., Lieber, E., and Hirschhorn, K. (1971). Trisomy 22: a clinical entity. Journal ofPediatrics, 79, 12. copyright. Discussion Omar, S. A., Sanger, R. G., and Connell, G. M. (1974). Trisomy 22: a clinically identifiable syndrome. In New Chromosomal and Malformation Syndromes, pp. 241-245. Despite the fact that our proband has trisomy oftotal, Ed. by Daniel Bergsma. Stratton Intercontinental, New York. non-deleted chromosome 22, she is mildly affected. Penchaszadeh, V. B., and Coco, R. (1975). Trisomy 22. Two Her normal facial features and lack of anal atresia, new cases and delineation of the phenotype. Journal of congenital heart defect, cleft palate, hip abnormalities, , 12, 193. and other skeletal defects make her probably the least Perez-Castillo, A., Abrisqueta, J. A., Martin-Lucas, M. A.,http://jmg.bmj.com/ Goday, G., Del Mazo, J., and Aller, V. (1975). A new severely affected patient with trisomy 22 reported contribution to the study of 22 trisomy. Humangenetik, 30, to date. The presence of coloboma of the iris, the 265-271. so-called 'cat eye anomaly', is another unique Punnett, H. H., Kistenmacher, M. L., Toro-Sola, A., and finding, since in 18 reported cases of full trisomy 22 Kohn, G. (1973). Quinacrine fluorescence and Giemsa in trisomy 22. Theoretical and Applied Genetics, 43, 134-138. reliably identified by banding techniques (Bass et al., Schachenmann, G., Schmid, W., Fraccaro, M., Mannini, 1973; Buffoni et al., 1974; German et al., 1971; Hsu A., Tiepolo, L., Perona, G. P., and Sartosi, S. (1965).

et al., 1971; Omar et al., 1974; Penchaszadeh and Chromosomes in coloboma and anal atresia. Lancet, 2,290. on September 27, 2021 by guest. Protected Coco, 1975; Perez-Castillo et al., 1975; Punnett et al., Seabright, M. (1971). A rapid banding technique for human chromosomes. Lancet, 2, 971-972. 1973; Uchida et al., 1968; Uchida and Brynes, 1976; Uchida, I. A., and Brynes, E. M. (1976). Confirmation of Zackai et al., 1973), none possessed this feature trisomy 22 with flourescence banding. American Journal of (see Table). This observation leads us to suggest that Human Genetics, 28, 189. the term '' should be applied either Zackai, E., Aronson, M., Kohn, G., Moorhead, P., and Mellman, M. (1973). Familial trisomy 22 (abstract). to both partial trisomy 22 (47,+22q-) and full American Journal ofHuman Genetics, 25 (6), 89A. trisomy 22 (47,+22), or better not at all, retaining Zellweger, H., Ionasescu, V., and Simpson, J. (1975). Trisomy the descriptive terms 'trisomy 22' and 'trisomy 22. Journal de Gnentique Humaine, 23, 65-75. 22q-'.

We wish to express our gratitude to Carmen Yasis, Requests for reprints to Dr J. Cervenka, Health Karen D. Kurvnik, and Lynn Davis for their Sciences Unit A 16-133, University of Minnesota, valuable assistance. Minneapolis, Minnesota 55455, U.S.A.