Cytologia
Anopthalmia
and
with
a
Ring
Other
Anomalies
Chromosome
Philip
Chang2,
R.
A.
Rottino5,
M.
No.
17•`181
J. and
1975
Associated
Perciaccante3, O. Behanna2
40: 135-140,
D.
Miller4,
Bailey2
ReceivedJune 18, 1973 A ring chromosome number 17 or 18 was first reported by Wang et al. (1962). Since then, other examples of the same abnormality have been observed in associa tion with quite variable clinical manifestations. This is approximately the twenty fourth to twenty-fifth case of ring chromosome number 17 or 18 to be reported.
Case report The propositus, E. H., was born at 40 weeks gestation by an assisted frank breech extraction with multiple malformations. Birth weight was 2180 grams. The mother had taken Enovid for contraceptive purposes until one year prior to this, her first pregnancy. She had a negative reaction to a smallpox vaccination given between the second and third month after conception. At two weeks of age, he developed a mixed urinary tract infection, with peri pheral edema, elevated BUN (60mg%) and hemoconcentration. The hernatocrit was 62%, the leucocyte count 59,000per mm3, with 57 neutrophils, 42 lymphocytes, and one eosinophil per 100 cells. Serum albumin was 2.2 grams percent, and globulins 3.3 grams percent. The urine with a pH 6.0 and specific gravity of 1.012, was negative for sugar, acetone, and protein, despite 4+ bacteriuria and 1-2 WBC and RBC per high power field. An intravenous pyelogram showed no urinary tract abnormality. The urinary tract infection responded well to Tetracycline followed by Sulfi soxazole (Gantrinsin). However, at four weeks of age, bilateral peribronchiolar pneumonia developed. Tetracycline therapy was of little value. The course was marked by vomiting and progressive diarrhea, leading to death at 6 weeks (42 days) of age. Postmortem examination revealed a 1720 gram male infant 50cm in length with absence of the left optic nerve and eyeball, shallow left orbit, increased sagittal diameter of the head, long thumbs, and valgus deformities of both feet. Bronchial pneumonia, interstitial and subpleural air emphysema of both lungs, with evidence of aspiration were present. Cerebral cortex, pons, cerebellum, and medulla showed 1 This paper was presentedon September8, 1971at the Fourth InternationalCongressof HumanGeneticsheld in Paris,France. Supportedby a grantfrom the U. S. PublicHealth ServiceHDO0516. 2 Dept. of Biology,CaliforniaStateCollege,Calif.,Pa. 3 Dept. of Pediatrics,St. Vincent'sHospitaland MedicalCenter,NewYork,N. Y. 4 Dept. of Obstetricsand Gynecology,Collegeof Physiciansand Surgeons,ColumbiaUni versity,New York, N. Y. 5 Dept. of Pathology,St. Vincent'sHospitaland MedicalCenter,NewYork,N. Y., U. S. A.
136
P. Chang, et al.
Fig.
Fig.
2.
Chromosome
complement
1.
Pedigree
from peripheral
Cytologia 40
of the propositus.
blood
culture
and karyotype
of the p
ropositus.
1975
Anopthalmia
and Other
Anomalies
Associated
With a Ringchromosome
137
normal architecture. The left olfactory tract appeared to be absent. The heart and urinary system showed no abnormalities. The testes and epididymis had a normal histological appearance. Spermatogonia were present. Family history Both parents are of Jewish ancestry with no known consanguinity (see pedigree in Fig. 1). The maternal ancestors were from Spain while the paternal ancestors were from Poland. Each parent has monozygotic male twin siblings. All siblings of the parents and their offspring are normal. One year after the death of the pro positus, a phenotypically
and karyotypically
normal son was born to the parents.
Fig. 3. Some shapes and forms of the ring chromosomefrom peripheralblood cultureof the propositus. Cytological study Sex chromatin was absent in a buccal smear stained with Cresyl violet. Chro mosome studies were carried out on cultured peripheral blood leucocytes, using standard methods. The chromosomes in 37 metaphase figures from the culture of the propositus were analyzed in detail. All 37 contained 45 normal chromosomes plus a typical ring chromosome which was present in place of one of the normal E group chromosomes, either 17 or 18. Two chromosomes 16 were present in all 37 cells. Two presumptive chromosomes 17 plus a single presumptive chromosome 18 (shorter in both long and short arms) were observed in 26 of the 37 cells, with no clear cut difference visible in the other 11 cells. In no cells, however, was there a single presumptive chromosome 17 and two presumptive chromosomes 18. There
138
P. Chang, et al.
Cytologia 40
fore, the ring chromosome probably arose from a chromosome 18, presumably by reunion of broken interstitial ends of short and long arms of this chromosome (Fig. 2). The ring chromosome which takes characteristic shapes and forms (Fig. 3), appears to be quite stable. Thus, it is present in every cell and shows no detectable variation in size. The frequency of persistent bridges in telophase cells and the frequency of micronuclei of persistent bridges in interphase cells, both in culture and in post mortem tissues, are no higher than in controls. Cultured leucocytes from the clinically normal parents and younger brother had normal karyotypes. Discussion In man, ring chromosomes have been found both in vitro and in vivo, in various tissues, and in association with various malformations. The phenotypes of the twenty-four known cases with a ring chromosome 17 or 18 have been reported. (Wang et al. 1962, Genest et al. 1963, Lucas et al. 1963, Gropp et al. 1964, de Grou chy et al. 1965, Bernard et al. 1966, Lejeune et al. 1966, Aula et al. 1967, Mikelsaar et al. 1967, Palmer et al. 1967, Petit and Poncelet 1967, de Grouchy et al. 1968, Hooft et al. 1968, Leist et al. 1968, Sinha 1968, Richards et al. 1968, Cenani et al. 1969, Ricci et al. 1969, Dumars et al. 1970, Christensen et al. 1970 a. b., Chang et al. 1973). None of the abnormalities seen in these more than twenty cases can be con sidered characteristic of a ring chromosome 17 or 18. On the other hand, it is informative to compare with them the findings in patients with a partial deletion of the short arm of chromosome 17 or 18 (de Grouchy et al. 1966) and in patients with a partial deletion of the long arm of chromosome 17 or 18 (de Grouchy et al. 1964), since a ring chromosome has a deletion of part of each arm. For example, five have "rocker bottom feet" and three have atretic ear canals, deformities commonly seen in patients with a long arm deletion; fourteen have hypertelorism and/or epicanthic folds, features commonly seen in patients with a short arm deletion. The occurrence of some abnoramlities characteristic of a long arm deletion and others that are com monly seen in association with a short arm deletion, may turn out to be sufficiently characteristic of ring chromosome cases as to be almost diagnostic. In general, the types of abnormalities observed in the cases with a ring chromosome do not usually lead to antenatal mortality. This may account for the finding of equal numbers of affected males and females. However, in our case, since it caused the death of the patient, may be interpreted as the most severe case. These more than twenty cases do not provide any clue to the origin of the ring chromosome. In most cases, there was no history of X-irradiation or drug treatment before or during pregnancy. The small pox vaccination of the mother of the present case probably occurred too late in pregnency to have played any role. To our know ledge, this virus has not been implicated in the induction of chromosomal abnormal ities. The only suspicion in this case is that the mother took Enovid one year prior to the pregnancy. This might have been one of the causes for malformation to occur. In conclusion, more cases of these deformities should be reported so that they may be recorded and compared, thus contributing to the better understanding of this syndrome. Improved methods of fluorescence and Giemsa staining techniques
1975
Anopthalmia
may be useful
and Other Anomalies Associated with a Ring chromosome
for the eventual
mapping
of the short
and long arms
139
of chromosome
18 in the future.
Summary A white male infant was born at 40 week's gestation with multiple malformations and one eye missing. At two weeks of age, he developed a mixed urinary tract infection. At four weeks of age, bilateral peribronchiolar pneumonia developed . The course was marked by vomiting and progressive diarrhea, leading to death at six weeks (42 days) of age. Postmortem examination revealed the absence of the left optic nerve and eyeball with shallow left orbit, among other abnormalities . Sex chromatin was negative. All 37 metaphases analysed on leucocyte cultures contain 45 normal chromosomes plus a typical ring chromosome, which is present in place of one of the E group chromosomes, either no. 17 or no. 18. Judging morphologi cally, the ring chromosome probably arose from a chromosome no. 18. References Aula, P., Gripenberg, U., Hjelt, L., Kivalo, E., Leisti, J., Palo, J., Schoultz, B. von and Suomalainin, E.1967. Two cases with a ring chromosome in group E. Acta Neurol. Scand. 43: 51. Bernard, R., Stakl, A., Girard, F., Hartung, N. and Brusquet, T. 1966. Encephalopathie avec dysmorphie complexe et chromosome 17-18 en anneau. Ann. Pediat. 13: 525. Cenani, A., Pfieffer, R. A. and Simon, H. A. 1969. Ring chromosome 18 (46, XX, 18r) Hu mangenetik 7: 351. Chang, P., Perciaccante, R., Miller, O. J., Rottino, A., Behanna, M. and Bailey, D. 1974. Ano phalmia and other anomalies associated with a ring chromosome no. 17-18. (present paper). Christensen, K. R., Friedrich, U., Jacobsen, P., Jensen, K., Nielsen, J. and Tsuboi, T. 1970. Ring chromosome 18 in mother and daughter. J. Mental Defic. Res. 14: 49. Dumars, K. W., Carnahan, L. G. and Barrett, R. V. 1970. Median facial cleft associated with ring E chromosome. J. Med. Genet. 7: 86. Genest, P., Leclerc, R. and Auger, C. 1963. Ring chromosome and partial translocation in the same cell. Lancet 1: 1426. Gripenberg, U. 1967. The cytological behavior of a human ring chromosome. Chromosoma (Berl.) 20: 284. Gropp, A., Jussen, A. and Ofleringer, K. 1964, Multiple congenital anomalies associated with a partially ring-shaped chromosome probably derived from chromosome number 18 in man. Nature 202: 829. Grouchy, J. de 1965. Chromosome 18: a topological approach. J. Pediat. 66: 414. -, Bonette, J. and Salmon, Chl. 1966. Deletion du bras court du chromosome 18. Ann. Genet. 9, 19. -, Herrault, A. and Cohen-Solal, J. 1968. Une observation de chromosome 18 en anneau (18 r). Ann. Genet. (Paris) 11: 33. - , Leveque, B., Debauchez, C., Lamy, M. and Maire, J. 1964. Chromosome 17-18 en anneau et malformations congenitale chez une fille. Ann. Genet. (Paris) 7: 17. Hooft, C., Haentjens, P., Orye, E., Kluyskens, P. and D'Hont, G. 1968. Chromosome 18 en an neau. Act Pediat. (Belg.) 22: 69. Kistenmacher, M. and Punnett, H. 1970. Comparative behavior of ring chromosomes. Amer. J. Hum. Genet. 22: 204. Leisti, J., Gripenberg, U., Kiralo, E., Palo, J., Schoultz, B. von and Suomalainin, E. 1968. Two
140
P. Chang, et al.
Cytologia 40
patients with a 46, XX, Er chromosome constitution. Acta Pediat. Scand. 57: 441. Lejeune, J., Rethore, N-O., Berger, R., Baheux, G. and Chabrun, J. 1966. Sur un cas de chromo some 18 en anneau. Ann. Genet. (Paris) 9: 173. Lucas, M., Demp, N. H., Ellis, J. E. and Marshall, R. 1963. A small autosomal ring chromosome in a female infant with congenital malformations. Ann. Hum. Genet. 27: 189. Mikelsaar, A. V. N., Tulvik, T. A. and Sitska, M. E. 1967. A ring shaped chromosome (presuma bly no. 18) and its bearing on the multiple congenital anomalies in man. Genetika 5: 63. Palmer, C., Fareed, N. and Merrit, A. D. 1967. Ring chromosome 18 in a patient with multiple anomalies. J. Med. Genet. 4: 117. Petit, P. and Poncelet, R. 1967. Un nouveau fac de chromosome 18 en anneau (18r). Ann. Genet. (Paris) 10: 134. Ricci, N., Dallapiccola, B., Ventimiglia, B. and Petro, G. 1969. Cromosoma 18 ad anello. Acta Genet. Med. Genellol 19: 430. Richards, B. W. and Hobbs, J. R. 1968. IgA and ring-18 chromosome. Lancet 1: 1426. Sinha, A. K. 1968. Human ring chromosome syndromes. An "E: ring associated with an abnor mal phenotype. Acta Genet. Med. Gemellol. 17: 487. Wang, H. C., Melnyk, J., McDonald, L. T., Uchida, I. A ., Carr, D. H. and Goldberg, B. 1962. Ring chromosome in human beings. Nature (Lond.) 195: 733. Wertelecki, W., Schindler, A. M. and Gerald, B. S. 1966. Partial deletion of chromosome 18. Lancet 2: 641.
Anopthalmia
and
with
a
Ring
Other
Anomalies
Chromosome
Philip
Chang2,
R.
A.
Rottino5,
M.
No.
17•`181
J. and
1975
Associated
Perciaccante3, O. Behanna2
40: 135-140,
D.
Miller4,
Bailey2
ReceivedJune 18, 1973 A ring chromosome number 17 or 18 was first reported by Wang et al. (1962). Since then, other examples of the same abnormality have been observed in associa tion with quite variable clinical manifestations. This is approximately the twenty fourth to twenty-fifth case of ring chromosome number 17 or 18 to be reported.
Case report The propositus, E. H., was born at 40 weeks gestation by an assisted frank breech extraction with multiple malformations. Birth weight was 2180 grams. The mother had taken Enovid for contraceptive purposes until one year prior to this, her first pregnancy. She had a negative reaction to a smallpox vaccination given between the second and third month after conception. At two weeks of age, he developed a mixed urinary tract infection, with peri pheral edema, elevated BUN (60mg%) and hemoconcentration. The hernatocrit was 62%, the leucocyte count 59,000per mm3, with 57 neutrophils, 42 lymphocytes, and one eosinophil per 100 cells. Serum albumin was 2.2 grams percent, and globulins 3.3 grams percent. The urine with a pH 6.0 and specific gravity of 1.012, was negative for sugar, acetone, and protein, despite 4+ bacteriuria and 1-2 WBC and RBC per high power field. An intravenous pyelogram showed no urinary tract abnormality. The urinary tract infection responded well to Tetracycline followed by Sulfi soxazole (Gantrinsin). However, at four weeks of age, bilateral peribronchiolar pneumonia developed. Tetracycline therapy was of little value. The course was marked by vomiting and progressive diarrhea, leading to death at 6 weeks (42 days) of age. Postmortem examination revealed a 1720 gram male infant 50cm in length with absence of the left optic nerve and eyeball, shallow left orbit, increased sagittal diameter of the head, long thumbs, and valgus deformities of both feet. Bronchial pneumonia, interstitial and subpleural air emphysema of both lungs, with evidence of aspiration were present. Cerebral cortex, pons, cerebellum, and medulla showed 1 This paper was presentedon September8, 1971at the Fourth InternationalCongressof HumanGeneticsheld in Paris,France. Supportedby a grantfrom the U. S. PublicHealth ServiceHDO0516. 2 Dept. of Biology,CaliforniaStateCollege,Calif.,Pa. 3 Dept. of Pediatrics,St. Vincent'sHospitaland MedicalCenter,NewYork,N. Y. 4 Dept. of Obstetricsand Gynecology,Collegeof Physiciansand Surgeons,ColumbiaUni versity,New York, N. Y. 5 Dept. of Pathology,St. Vincent'sHospitaland MedicalCenter,NewYork,N. Y., U. S. A.
136
P. Chang, et al.
Fig.
Fig.
2.
Chromosome
complement
1.
Pedigree
from peripheral
Cytologia 40
of the propositus.
blood
culture
and karyotype
of the p
ropositus.
1975
Anopthalmia
and Other
Anomalies
Associated
With a Ringchromosome
137
normal architecture. The left olfactory tract appeared to be absent. The heart and urinary system showed no abnormalities. The testes and epididymis had a normal histological appearance. Spermatogonia were present. Family history Both parents are of Jewish ancestry with no known consanguinity (see pedigree in Fig. 1). The maternal ancestors were from Spain while the paternal ancestors were from Poland. Each parent has monozygotic male twin siblings. All siblings of the parents and their offspring are normal. One year after the death of the pro positus, a phenotypically
and karyotypically
normal son was born to the parents.
Fig. 3. Some shapes and forms of the ring chromosomefrom peripheralblood cultureof the propositus. Cytological study Sex chromatin was absent in a buccal smear stained with Cresyl violet. Chro mosome studies were carried out on cultured peripheral blood leucocytes, using standard methods. The chromosomes in 37 metaphase figures from the culture of the propositus were analyzed in detail. All 37 contained 45 normal chromosomes plus a typical ring chromosome which was present in place of one of the normal E group chromosomes, either 17 or 18. Two chromosomes 16 were present in all 37 cells. Two presumptive chromosomes 17 plus a single presumptive chromosome 18 (shorter in both long and short arms) were observed in 26 of the 37 cells, with no clear cut difference visible in the other 11 cells. In no cells, however, was there a single presumptive chromosome 17 and two presumptive chromosomes 18. There
138
P. Chang, et al.
Cytologia 40
fore, the ring chromosome probably arose from a chromosome 18, presumably by reunion of broken interstitial ends of short and long arms of this chromosome (Fig. 2). The ring chromosome which takes characteristic shapes and forms (Fig. 3), appears to be quite stable. Thus, it is present in every cell and shows no detectable variation in size. The frequency of persistent bridges in telophase cells and the frequency of micronuclei of persistent bridges in interphase cells, both in culture and in post mortem tissues, are no higher than in controls. Cultured leucocytes from the clinically normal parents and younger brother had normal karyotypes. Discussion In man, ring chromosomes have been found both in vitro and in vivo, in various tissues, and in association with various malformations. The phenotypes of the twenty-four known cases with a ring chromosome 17 or 18 have been reported. (Wang et al. 1962, Genest et al. 1963, Lucas et al. 1963, Gropp et al. 1964, de Grou chy et al. 1965, Bernard et al. 1966, Lejeune et al. 1966, Aula et al. 1967, Mikelsaar et al. 1967, Palmer et al. 1967, Petit and Poncelet 1967, de Grouchy et al. 1968, Hooft et al. 1968, Leist et al. 1968, Sinha 1968, Richards et al. 1968, Cenani et al. 1969, Ricci et al. 1969, Dumars et al. 1970, Christensen et al. 1970 a. b., Chang et al. 1973). None of the abnormalities seen in these more than twenty cases can be con sidered characteristic of a ring chromosome 17 or 18. On the other hand, it is informative to compare with them the findings in patients with a partial deletion of the short arm of chromosome 17 or 18 (de Grouchy et al. 1966) and in patients with a partial deletion of the long arm of chromosome 17 or 18 (de Grouchy et al. 1964), since a ring chromosome has a deletion of part of each arm. For example, five have "rocker bottom feet" and three have atretic ear canals, deformities commonly seen in patients with a long arm deletion; fourteen have hypertelorism and/or epicanthic folds, features commonly seen in patients with a short arm deletion. The occurrence of some abnoramlities characteristic of a long arm deletion and others that are com monly seen in association with a short arm deletion, may turn out to be sufficiently characteristic of ring chromosome cases as to be almost diagnostic. In general, the types of abnormalities observed in the cases with a ring chromosome do not usually lead to antenatal mortality. This may account for the finding of equal numbers of affected males and females. However, in our case, since it caused the death of the patient, may be interpreted as the most severe case. These more than twenty cases do not provide any clue to the origin of the ring chromosome. In most cases, there was no history of X-irradiation or drug treatment before or during pregnancy. The small pox vaccination of the mother of the present case probably occurred too late in pregnency to have played any role. To our know ledge, this virus has not been implicated in the induction of chromosomal abnormal ities. The only suspicion in this case is that the mother took Enovid one year prior to the pregnancy. This might have been one of the causes for malformation to occur. In conclusion, more cases of these deformities should be reported so that they may be recorded and compared, thus contributing to the better understanding of this syndrome. Improved methods of fluorescence and Giemsa staining techniques
1975
Anopthalmia
may be useful
and Other Anomalies Associated with a Ring chromosome
for the eventual
mapping
of the short
and long arms
139
of chromosome
18 in the future.
Summary A white male infant was born at 40 week's gestation with multiple malformations and one eye missing. At two weeks of age, he developed a mixed urinary tract infection. At four weeks of age, bilateral peribronchiolar pneumonia developed . The course was marked by vomiting and progressive diarrhea, leading to death at six weeks (42 days) of age. Postmortem examination revealed the absence of the left optic nerve and eyeball with shallow left orbit, among other abnormalities . Sex chromatin was negative. All 37 metaphases analysed on leucocyte cultures contain 45 normal chromosomes plus a typical ring chromosome, which is present in place of one of the E group chromosomes, either no. 17 or no. 18. Judging morphologi cally, the ring chromosome probably arose from a chromosome no. 18. References Aula, P., Gripenberg, U., Hjelt, L., Kivalo, E., Leisti, J., Palo, J., Schoultz, B. von and Suomalainin, E.1967. Two cases with a ring chromosome in group E. Acta Neurol. Scand. 43: 51. Bernard, R., Stakl, A., Girard, F., Hartung, N. and Brusquet, T. 1966. Encephalopathie avec dysmorphie complexe et chromosome 17-18 en anneau. Ann. Pediat. 13: 525. Cenani, A., Pfieffer, R. A. and Simon, H. A. 1969. Ring chromosome 18 (46, XX, 18r) Hu mangenetik 7: 351. Chang, P., Perciaccante, R., Miller, O. J., Rottino, A., Behanna, M. and Bailey, D. 1974. Ano phalmia and other anomalies associated with a ring chromosome no. 17-18. (present paper). Christensen, K. R., Friedrich, U., Jacobsen, P., Jensen, K., Nielsen, J. and Tsuboi, T. 1970. Ring chromosome 18 in mother and daughter. J. Mental Defic. Res. 14: 49. Dumars, K. W., Carnahan, L. G. and Barrett, R. V. 1970. Median facial cleft associated with ring E chromosome. J. Med. Genet. 7: 86. Genest, P., Leclerc, R. and Auger, C. 1963. Ring chromosome and partial translocation in the same cell. Lancet 1: 1426. Gripenberg, U. 1967. The cytological behavior of a human ring chromosome. Chromosoma (Berl.) 20: 284. Gropp, A., Jussen, A. and Ofleringer, K. 1964, Multiple congenital anomalies associated with a partially ring-shaped chromosome probably derived from chromosome number 18 in man. Nature 202: 829. Grouchy, J. de 1965. Chromosome 18: a topological approach. J. Pediat. 66: 414. -, Bonette, J. and Salmon, Chl. 1966. Deletion du bras court du chromosome 18. Ann. Genet. 9, 19. -, Herrault, A. and Cohen-Solal, J. 1968. Une observation de chromosome 18 en anneau (18 r). Ann. Genet. (Paris) 11: 33. - , Leveque, B., Debauchez, C., Lamy, M. and Maire, J. 1964. Chromosome 17-18 en anneau et malformations congenitale chez une fille. Ann. Genet. (Paris) 7: 17. Hooft, C., Haentjens, P., Orye, E., Kluyskens, P. and D'Hont, G. 1968. Chromosome 18 en an neau. Act Pediat. (Belg.) 22: 69. Kistenmacher, M. and Punnett, H. 1970. Comparative behavior of ring chromosomes. Amer. J. Hum. Genet. 22: 204. Leisti, J., Gripenberg, U., Kiralo, E., Palo, J., Schoultz, B. von and Suomalainin, E. 1968. Two
140
P. Chang, et al.
Cytologia 40
patients with a 46, XX, Er chromosome constitution. Acta Pediat. Scand. 57: 441. Lejeune, J., Rethore, N-O., Berger, R., Baheux, G. and Chabrun, J. 1966. Sur un cas de chromo some 18 en anneau. Ann. Genet. (Paris) 9: 173. Lucas, M., Demp, N. H., Ellis, J. E. and Marshall, R. 1963. A small autosomal ring chromosome in a female infant with congenital malformations. Ann. Hum. Genet. 27: 189. Mikelsaar, A. V. N., Tulvik, T. A. and Sitska, M. E. 1967. A ring shaped chromosome (presuma bly no. 18) and its bearing on the multiple congenital anomalies in man. Genetika 5: 63. Palmer, C., Fareed, N. and Merrit, A. D. 1967. Ring chromosome 18 in a patient with multiple anomalies. J. Med. Genet. 4: 117. Petit, P. and Poncelet, R. 1967. Un nouveau fac de chromosome 18 en anneau (18r). Ann. Genet. (Paris) 10: 134. Ricci, N., Dallapiccola, B., Ventimiglia, B. and Petro, G. 1969. Cromosoma 18 ad anello. Acta Genet. Med. Genellol 19: 430. Richards, B. W. and Hobbs, J. R. 1968. IgA and ring-18 chromosome. Lancet 1: 1426. Sinha, A. K. 1968. Human ring chromosome syndromes. An "E: ring associated with an abnor mal phenotype. Acta Genet. Med. Gemellol. 17: 487. Wang, H. C., Melnyk, J., McDonald, L. T., Uchida, I. A ., Carr, D. H. and Goldberg, B. 1962. Ring chromosome in human beings. Nature (Lond.) 195: 733. Wertelecki, W., Schindler, A. M. and Gerald, B. S. 1966. Partial deletion of chromosome 18. Lancet 2: 641.
