Clinicul Genetics 1978: 13: 237-240
Two cases of an abnormal short arm of chromosome 8 (8p+) associated with mental retardation KARIN HONGELL,SAKARIKNUUTILA AND TUOMAS WESTERMARCK
Department of Genetics, University of Helsinki, Helsinki, and Research Department, Rinnekoti Institution for the Mentally Retarded, Espoo, Finland Morphologically similar chromosome anomalies, 8 p + , were found in two inmates of an institution for the mentally retarded. Analysis of the G- and R-banding patterns showed that the first subject had a duplication of region p2 of chromosome 8; the second subject had an insertion of an unidentified chromosome segment at 8pll. Both subjects were severely mentally retarded. The physical malformations were more severe in the second subject than in the first, who had only minor signs. The dermatoglyphics are recorded. Received 18 August, accepted for publication 12 September 1977
A number of anomalies of chromosome 8 have recently been reported. Of these, trisomy for the complete chromosome is designated as a recognizable syndrome. Partial trisomies for the short arm and for the long arm, respectively, have been reported to be connected with certain clinical features (RethorC et al. 1977). We report two new cases of aberrations of chromosome 8, found among the inmates of an institution for the mentally retarded. In both cases the short arm of this chromosome was exceptionally long. Case Reports
Subject 1 is an adult male who was born in 1953. At his birth, his mother was 27 and his father 25 years old. Both parents and an older brother were healthy. The birth weight was 2,970 g and length 50 cm. The child was cyanotic immediately after birth, and icteric for 1 month; he thrived poorly. His physical and social development
were delayed, and mental retardation was diagnosed at the age of 2 years. Convulsions were reported on one occasion during childhood. As an adult, his height is 175 cm, weight 43.5 kg, and head circumference 54 cm. Minor physical anomalies are present: higharched palate, mild hypertelorism and large, slightly low-set ears, with poor lobulation. The shape of the mandible is square and the chin is rather big. The mouth is large with a broad philtrum, and the lower lip is somewhat everted (Fig. la). A small benign tumor has been removed from his left cheek. The external genitalia are normal, and so were the EEG and X-ray findings. There are no pathological reflexes. His balance reactions are good, although his movements are rather slow. He is able to speak some short sentences, but mental retardation is profound. Subject 2 is a 10-year-old girl, the elder of two siblings. She was born after 37 weeks
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Fig. 1. (a) Case 1 , (b) Case 2, (c) Case 2 in typical
sitting position, with abducted thighs.
of gestation, her birth weight being 2,020 g. The mother was 25 and the father 22 years old at the time of the birth. Both parenb are healthy. The child was cyanotic immediately after birth, and the cyanosis persisted; she was found to have dcxtrocardia. At 2 months, examinations revealed hydro-
nephrosis on the right side, which was treated by ureterocystoneostomy and ureterocutaneostomy. Her physical and mental development were slow. At 10 years, her height is 106 cm, weight 16 kg and head circumference 49.5 cm. She cannot walk or stand without support,
TWO CASES OF 8 p f CHROMOSOME ANOMALY
a
b
C Fig. 2. Diagram and microphotographs of banded abnormal chromosomes No. 8 and their normal homologues. (a) Case 1, G-band, (b) Case 2, G-band, (c) Case 2. R-band.
but crawls on her hands in a sitting position with abducted thighs (Fig. lc). Several physical abnormalities are present: bilateral pes equinus, prominent forehead, higharched palate, micrognathia, protruding ears, incurved fifth fingers and proximally inserted thumbs. A bilateral inguinal hernia has been surgically corrected on the left side. Her balance reactions are poor, and she has spastic tetraplegia. She has brisk, multiple leg reflexes and some athetotic arm and leg movements; her limbs are hypertonic and difficult to straighten out. She also has slight convergent strabismus. She is unable to speak, and is severely mentally retarded. Cytogenetic findings I n both subjects, all the cells studied from
239
peripheral lymphocyte cultures contained 45 chromosomes. One chromosome in the Cgroup was abnormal, the short arm being longer than in any of the other C-group chromosomes. For identification of the abnormal chromosome, G- and R-banding techniques werc used. In both cases the abnormal chromosome was found to be No. 8. In Case 1, there was a direct duplication of the distal region p2 of chromosome 8 (Fig. 2a). The short arm of the abnormal chromosome, measured from microphotographs, was longer than the normal No. 8 by about one-third. The centromere index 1.1 was 39.3 k 0.9, compared with 29.8 for the normal homologue. The other chromosomes in the complement were all normal, as were the chromosomes of the parents and the brother of the propositus. The karyotype of Case 1 is 46,XY,dup(8p)(p21 +p23). In Case 2, the lengthening of 8p was due to additional material inserted in the proximal part of the short arm at band 8 p l l (Fig. 2b, c). The other chromosomes in the complement were normal and we have not been able to trace the origin of this extra material. The chromosomes of the parents were normal. The designation of the karyotype in Case 2 is 46,XX,ins(8;?)(pll;?). Derrnatoglyphic Findings I n Cuse I , the fourth and fifth fingers had ulnar loops, and all the other fingertips had arches. The total ridge count (TRC) was 14. In the right palm there was an axial triradius in the t’ position and an ulnar loop in the hypothenar area. The left palm had a loop in the IVth interdigital area. The A line exited at 5’ on the right and at 4 on the left palm.
In Case 2, all fingertips had ulnar loops except the left index finger, which had a tented arch. The TRC was 87. The left palm had a simian crease, and the right
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palm had loops in interdigital areas 111 and 1V. The A-line exit was at 5’ on both palms. Discussion and Conclusion
Although the two aberrant chromosomes No. 8 presented here are morphologically similar, the banding patterns revealed that the two subjects are, in fact, trisomic for different chromosome segments. The chromosome aberration in Case 1 has been interpreted as a duplication of region 2 of the short arm of chromosome 8. Thus this patient is trisomic for a part of 8p. A cytogcnctically similar case, dup (8p21+8p23), was studied for gene-mapping purposes by George & Francke (1976), but the phenotype of this subject was not described. Subjects with trisomy for the short arm of chromosome 8 have been described by Rosenthal et al. (1973), Yanagisawa (1973), Chiyo et al. (1975), Welebcr ct al. (1976) and by Rethore et al. (1977). These trisomies comprised, however, a larger part of 8p than the duplicated segment in our Case 1. Cases 7 and 8 of Rethore et al. (1977) were, in addition, monosomic for the most distal segment of the short arm, 8p23. Thc malformations in the cited cases of 8p trisomy were not severe. Microcephaly, a thick nose, large mouth, everted lower lip, square jaw, and arches on the fingertips have been regarded as characteristic for Xp trisomy (RetharC et al. 1977). In our Case 1, the skull is of normal size and the nose is not exceptional. The large mouth, the somewhat everted lower lip, the squareshaped jaw and the preponderance of arches on the fingertips are in accordance with the findings of Rethore et al. (1977). These signs, however, have not been reported in the other cases of trisomy Xp cited above. The phenotype of our Case 2 does not
resemble the published cases of 8p+ chromosome anomaly. We think it may be a sporadic case of trisomy for another part of the chromosome set. The two cases of 8p+ anomaly presented here do not have any notable phenotypic similarity; this is quitc in accordance with our interpretation of the cytogenetic findings. Acknowledgement
We are grateful to Dr Ulla Gripenberg for her helpful discussion and critical rcadiiig of the manuscript. References
Chiyo, H.-A., Y. Nakagome, 1. Matsui, Y. Kuroki, H. Kobayashi & K. Ono (1975). Two cases of 8p trisomy in one sibship. Clin. Genet. I, 328-333. George, D. L. & U. Francke (1976). Gene dose effect: regional mapping of human glutathione reductase on chromosome 8. Cytogertet. Cell Genet. 17, 282-286.
Rethork, M.-O., A. Aurias, 3. Couturier, B. Dutrillaux, M. Prieur & J. Lejeune (1977). Chromosome 8: trisomie complkte et trisomie segmentaires. Ann. GPnPt. 20, 5-11. Rosenthal, I. M., E. Krmpotic, M. Bocian & K. Szego (1973). Trisomy of the short arm of chromosome 8: Association with translocation between chromosomes 8 and 22 46,XY, 22-,t(8p22q)+. Clin. Genet. 4, 507-516. Weleber, R. G., R. S . Verma, W. 3. Kimberling, H. G. Fieger Jr. & H. A. Lubs (1976). Duplication-deficiency of the short arm of chromosome 8 following artificial insemination. Ann. GPnPt. 19, 241-247. Yanagisawa, S. (1973). Partial trisomy 8: further observation of a familial C/G translocation chromosome identified by the Qstaining methods. 1. nzerrt. Defir. Res. 17, 28-32.
Address: Karin Hongell, Ph.lic. Department of Generirs University of Helsinki P . Rautatiekatu 13 SF-OOIOO Helsinki 10 Finland
Two cases of an abnormal short arm of chromosome 8 (8p+) associated with mental retardation KARIN HONGELL,SAKARIKNUUTILA AND TUOMAS WESTERMARCK
Department of Genetics, University of Helsinki, Helsinki, and Research Department, Rinnekoti Institution for the Mentally Retarded, Espoo, Finland Morphologically similar chromosome anomalies, 8 p + , were found in two inmates of an institution for the mentally retarded. Analysis of the G- and R-banding patterns showed that the first subject had a duplication of region p2 of chromosome 8; the second subject had an insertion of an unidentified chromosome segment at 8pll. Both subjects were severely mentally retarded. The physical malformations were more severe in the second subject than in the first, who had only minor signs. The dermatoglyphics are recorded. Received 18 August, accepted for publication 12 September 1977
A number of anomalies of chromosome 8 have recently been reported. Of these, trisomy for the complete chromosome is designated as a recognizable syndrome. Partial trisomies for the short arm and for the long arm, respectively, have been reported to be connected with certain clinical features (RethorC et al. 1977). We report two new cases of aberrations of chromosome 8, found among the inmates of an institution for the mentally retarded. In both cases the short arm of this chromosome was exceptionally long. Case Reports
Subject 1 is an adult male who was born in 1953. At his birth, his mother was 27 and his father 25 years old. Both parents and an older brother were healthy. The birth weight was 2,970 g and length 50 cm. The child was cyanotic immediately after birth, and icteric for 1 month; he thrived poorly. His physical and social development
were delayed, and mental retardation was diagnosed at the age of 2 years. Convulsions were reported on one occasion during childhood. As an adult, his height is 175 cm, weight 43.5 kg, and head circumference 54 cm. Minor physical anomalies are present: higharched palate, mild hypertelorism and large, slightly low-set ears, with poor lobulation. The shape of the mandible is square and the chin is rather big. The mouth is large with a broad philtrum, and the lower lip is somewhat everted (Fig. la). A small benign tumor has been removed from his left cheek. The external genitalia are normal, and so were the EEG and X-ray findings. There are no pathological reflexes. His balance reactions are good, although his movements are rather slow. He is able to speak some short sentences, but mental retardation is profound. Subject 2 is a 10-year-old girl, the elder of two siblings. She was born after 37 weeks
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Fig. 1. (a) Case 1 , (b) Case 2, (c) Case 2 in typical
sitting position, with abducted thighs.
of gestation, her birth weight being 2,020 g. The mother was 25 and the father 22 years old at the time of the birth. Both parenb are healthy. The child was cyanotic immediately after birth, and the cyanosis persisted; she was found to have dcxtrocardia. At 2 months, examinations revealed hydro-
nephrosis on the right side, which was treated by ureterocystoneostomy and ureterocutaneostomy. Her physical and mental development were slow. At 10 years, her height is 106 cm, weight 16 kg and head circumference 49.5 cm. She cannot walk or stand without support,
TWO CASES OF 8 p f CHROMOSOME ANOMALY
a
b
C Fig. 2. Diagram and microphotographs of banded abnormal chromosomes No. 8 and their normal homologues. (a) Case 1, G-band, (b) Case 2, G-band, (c) Case 2. R-band.
but crawls on her hands in a sitting position with abducted thighs (Fig. lc). Several physical abnormalities are present: bilateral pes equinus, prominent forehead, higharched palate, micrognathia, protruding ears, incurved fifth fingers and proximally inserted thumbs. A bilateral inguinal hernia has been surgically corrected on the left side. Her balance reactions are poor, and she has spastic tetraplegia. She has brisk, multiple leg reflexes and some athetotic arm and leg movements; her limbs are hypertonic and difficult to straighten out. She also has slight convergent strabismus. She is unable to speak, and is severely mentally retarded. Cytogenetic findings I n both subjects, all the cells studied from
239
peripheral lymphocyte cultures contained 45 chromosomes. One chromosome in the Cgroup was abnormal, the short arm being longer than in any of the other C-group chromosomes. For identification of the abnormal chromosome, G- and R-banding techniques werc used. In both cases the abnormal chromosome was found to be No. 8. In Case 1, there was a direct duplication of the distal region p2 of chromosome 8 (Fig. 2a). The short arm of the abnormal chromosome, measured from microphotographs, was longer than the normal No. 8 by about one-third. The centromere index 1.1 was 39.3 k 0.9, compared with 29.8 for the normal homologue. The other chromosomes in the complement were all normal, as were the chromosomes of the parents and the brother of the propositus. The karyotype of Case 1 is 46,XY,dup(8p)(p21 +p23). In Case 2, the lengthening of 8p was due to additional material inserted in the proximal part of the short arm at band 8 p l l (Fig. 2b, c). The other chromosomes in the complement were normal and we have not been able to trace the origin of this extra material. The chromosomes of the parents were normal. The designation of the karyotype in Case 2 is 46,XX,ins(8;?)(pll;?). Derrnatoglyphic Findings I n Cuse I , the fourth and fifth fingers had ulnar loops, and all the other fingertips had arches. The total ridge count (TRC) was 14. In the right palm there was an axial triradius in the t’ position and an ulnar loop in the hypothenar area. The left palm had a loop in the IVth interdigital area. The A line exited at 5’ on the right and at 4 on the left palm.
In Case 2, all fingertips had ulnar loops except the left index finger, which had a tented arch. The TRC was 87. The left palm had a simian crease, and the right
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HONGELL, KNUUTILA AND WESTERMARCK
palm had loops in interdigital areas 111 and 1V. The A-line exit was at 5’ on both palms. Discussion and Conclusion
Although the two aberrant chromosomes No. 8 presented here are morphologically similar, the banding patterns revealed that the two subjects are, in fact, trisomic for different chromosome segments. The chromosome aberration in Case 1 has been interpreted as a duplication of region 2 of the short arm of chromosome 8. Thus this patient is trisomic for a part of 8p. A cytogcnctically similar case, dup (8p21+8p23), was studied for gene-mapping purposes by George & Francke (1976), but the phenotype of this subject was not described. Subjects with trisomy for the short arm of chromosome 8 have been described by Rosenthal et al. (1973), Yanagisawa (1973), Chiyo et al. (1975), Welebcr ct al. (1976) and by Rethore et al. (1977). These trisomies comprised, however, a larger part of 8p than the duplicated segment in our Case 1. Cases 7 and 8 of Rethore et al. (1977) were, in addition, monosomic for the most distal segment of the short arm, 8p23. Thc malformations in the cited cases of 8p trisomy were not severe. Microcephaly, a thick nose, large mouth, everted lower lip, square jaw, and arches on the fingertips have been regarded as characteristic for Xp trisomy (RetharC et al. 1977). In our Case 1, the skull is of normal size and the nose is not exceptional. The large mouth, the somewhat everted lower lip, the squareshaped jaw and the preponderance of arches on the fingertips are in accordance with the findings of Rethore et al. (1977). These signs, however, have not been reported in the other cases of trisomy Xp cited above. The phenotype of our Case 2 does not
resemble the published cases of 8p+ chromosome anomaly. We think it may be a sporadic case of trisomy for another part of the chromosome set. The two cases of 8p+ anomaly presented here do not have any notable phenotypic similarity; this is quitc in accordance with our interpretation of the cytogenetic findings. Acknowledgement
We are grateful to Dr Ulla Gripenberg for her helpful discussion and critical rcadiiig of the manuscript. References
Chiyo, H.-A., Y. Nakagome, 1. Matsui, Y. Kuroki, H. Kobayashi & K. Ono (1975). Two cases of 8p trisomy in one sibship. Clin. Genet. I, 328-333. George, D. L. & U. Francke (1976). Gene dose effect: regional mapping of human glutathione reductase on chromosome 8. Cytogertet. Cell Genet. 17, 282-286.
Rethork, M.-O., A. Aurias, 3. Couturier, B. Dutrillaux, M. Prieur & J. Lejeune (1977). Chromosome 8: trisomie complkte et trisomie segmentaires. Ann. GPnPt. 20, 5-11. Rosenthal, I. M., E. Krmpotic, M. Bocian & K. Szego (1973). Trisomy of the short arm of chromosome 8: Association with translocation between chromosomes 8 and 22 46,XY, 22-,t(8p22q)+. Clin. Genet. 4, 507-516. Weleber, R. G., R. S . Verma, W. 3. Kimberling, H. G. Fieger Jr. & H. A. Lubs (1976). Duplication-deficiency of the short arm of chromosome 8 following artificial insemination. Ann. GPnPt. 19, 241-247. Yanagisawa, S. (1973). Partial trisomy 8: further observation of a familial C/G translocation chromosome identified by the Qstaining methods. 1. nzerrt. Defir. Res. 17, 28-32.
Address: Karin Hongell, Ph.lic. Department of Generirs University of Helsinki P . Rautatiekatu 13 SF-OOIOO Helsinki 10 Finland
