Clinical Genetics 1976: 9: 250-254
Partial trisomy of the long arm of chromosome 7 A. AL SAADIAND HASSAN A. MOGHADAM Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak. Michigan, U S A . A baby with partial trisomy 7, 46, XY,t (5;7) (q35;q31) resulting from a familial translocation (5qf,7q -) is reported. The clinical abnormalities of this case closely resemble those of previously reported cases of partial trisomy 7. It is suggested that partial trisomy 7 may represent a clinical entity.
Received 5 June, accepted for publication 2 July 1975
Correct identification of chromosomal abnormalities by banding techniques is now a reality. Several examples of structural abnormality in the C-group have been precisely identified using the quinacrine and/or the Giemsa banding techniques. Partial trisomy of the long arm of chromosome 7 has been reported to result from translocations between chromosomes 7 and 14 (Alfi et al. 1973), 7 and 21 (Vogel et al. 1973). 7 and 12 (Carpentier et al. 1972), and 7 and 3 (Grace et al. 1973). In this report we present a case of partial trisomy 7 (7q3I + 7qter) resulting from a familial balanced translocation (5q+ ,7q-). The clinical findings are compared with those previously published in partial trisomy 7, and the clinical syndrome is discussed. Case Report
This male infant (111-5, Fig. 1) was born after full-term pregnancy to a gravida 1, para 0, 29-year-old white mother and a 29-year-old father. The baby was born elsewhere and was transferred to William
Beaumont Hospital at 8 h of age for further evaluation of malformations and breathing difficulty. The date of conception was uncertain because of irregular menstrual periods. The couple had been married for a little over 2 years, during which time no contraceptives were used. The pregnancy was uneventful; the mother took no drugs other than iron and vitamins and had no irradiation other than a set of dental roentgenograms. No history of miscarriages or malformed children was known in the mother’s family. The mother had had some vaginal spotting 2 weeks before delivery, but examination had revealed nothing unusual. The infant was delivered with the aid of forceps after a labor lasting 11 h. The baby’s weight was 2,156 g, length 48.5 cm and head circumference 36.8 cm. He was cyanotic and apneic, and intubation was necessary to maintain respiration. The Apgar values were 5 at 1 min and 6 at 10 min. Physical examination showed an abnormally shaped head, in which the parietal and occipitaI bones were more prominent than the frontal.
P A R T I A L T R I S O M Y OF T H E L O N G A R M O F C H R O M O S O M E 7
251
I
Fig. 1. Family pedigree. Empty circles or squares: normal karyotype. Half-shaded circles or squares: carriers of 5q+, 7q- translocations. Full square: partial trisomy 7q.
There were overriding of bones and a cephalohematoma in the left parietal area. The ears were malformed and low-set (Fig. 2). The bridge of the nose was flattened, and he had hypertelorism. Bilateral cleft palate and micrognathia were also present.
The sternum was unusually short. Heart tones were regular, and the cardiac rate was approximately 200/min. No pulmonary abnormalities were evident. The Moro reflex was positive, and the grasping reflex and sucking were poor. The fifth finger and the thumb were clenched over the other fingers. No simian creases were found. The baby had rocker-bottom feet. The baby was treated with Digoxin and Lasix because of heart failure and pulmonary edema. He died 20 h after birth. No additional gross malformations were encountered at postmortem examination, and microscopic examination of the major organs revealed no histologic abnormalities. Cytogenetlc Studies
Flg. 2. Proband shortly after death.
Chromosome preparations were done on peripheral leukocytes from the propositus (111-5) before his death and from all available relatives (Fig. 1) by using a modified technique of Moorehead et al. (1960). The slides were air-dried for a week, trypsinized with 0.025 % trypsin in Ca++- and Mg++-freeTyrode buffer for 20-30 s, and stained with Giemsa at pH 6.8 (Harleco 1 ml stock, 49 ml phosphate buffer). Each of the 30 examined cells of the propositus contained a long marker chromo-
252
SAADI AND MOGHADAM
Fig. 3. A representative karyotype of the proband showing the long chromosome 5 which consists of chromosome 5 and a portion of the long arm of chromosome 7.
some, which was subsequently identified as chromosome 5q+ (Fig. 3). The father (11-3), the paternal grandmother (I-l), and aunt (11-2) and a cousin (111-3) were all found to have the long chromosome 5q+ and a short chromosome 7 (7q-). The breakpoint on the long arm of chromosome 7 (Fig. 4) appears to have occurred in band 7q31 (Paris Conference, 1972). Since the father, the paternal grandmother, the aunt and the cousin each presumably carry a reciprocal translocation, another break must have taken place at the telomere of chromosome 5. However, this point cannot be confirmed, since most of the distal bands, 5q33 to 5q34, seem to be present in the rearranged chromosome 5q . The presumed breakpoint in chromosome 5 might have occurred, therefore, in the terminal band 5q35.
+
The baby had inherited the 5q+ chromosome and a normal no. 7 from his father and a normal no. 7 from his mother, and was therefore trisomic for the portion of the long arm of chromosome 7q31+7qter. The suggested designation of this translocation would be 46,XY,t (5;7) (q35;q31) in the short system and 46,XY,t (5;7) (5pter-t 5q35: :7q31+7qter; 7pter+7q31: :5q35+ 5qter) in the detailed system. Discussion
Partial trisomy for the long arm of chromosome 7 has been reported earlier (Carpentier et al. 1972, Alfi et al. 1973, Grace et al. 1973, Vogel et al. 1973). However, this is the first case known to us that resulted from a reciprocal translocation involving chromosomes 5q and 7q.
PARTIAL TRISOMY OF THE LONG ARM OF CHROMOSOME 7
Fig. 4. A representative kaiyotype of the paternal grandmother showing the 5q+, 7q-
All reported cases of partial 7q trisomy, including this one, seem to have had several common malformations. They include cleft palate, micrognathia, low-set and malformed ears, hypertelorism and large tongue, and are assumed to be the result of the excess chromosomal material. The extra material in this and at least two previously reported cases (Alfi et al. 1973, Vogel et al. 1973) appears to be a portion of the long arm of the chromosome 7q31+7qter. In two other reported cases of partial trisomy 7q (Carpentier et al. 1972, Grace et al. 1973) the clinical abnormalitites appear to be in close agreement with this case, although the excess chromosomal material was more in one case (Carpentier et al. 1972) and less in the other (Grace et al. 1973). Although most of the clinical abnormalities found in the partial 7q trisomy are also found in other chrornosoma1 anomalies, partial trisomy 7q may,
253
translocation
nevertheless, represent a defined clinical entity. It should be noted here that the mother of this baby failed to become pregnant for more than 2 years despite her desire to become pregnant. This can be explained by the possibility of early abortion(s) of partial trisomy 7 conceptus. This explanation can also be applied to the two spontaneous abortions, both in the first trimester, of the aunt who is a carrier of the translocation. Acknowledgments
We would like t o thank Dr. Jay Bernstein for his review and criticism of the manuscript, and we also thank Ms. M. Madercic and Ms. S. Charzan for their skillful technical assistance.
SAADl AND MOGHADAM
254 References
Alfi, 0. S., G. N. Donne11 & S. L. Kramer (1973). Partial trisomy of the long arm of chromosome, no. 7. 1. med. Genet. 10, 187189. Carpentier, S., M. 0. Rethore & J. Lejeune (1972). Trisomie partielle 7q par translocation familiale. t(7,12) (q22,q24). Ann. Ge'nPt. 15, 283-286. Grace, E., G. R. Sutherland, G. D. Start & A. D. Bain (1973). Partial trisomy of 7q resulting from a familial translocation. Ann. GinPt. 16, 51-54. Moorehead, P. S., P. C. Nowell, W. J. Mellman, D. M. Battips & D. A. Hungerford
(1960). Chromosome preparations of leukocytes cultured from human peripheral blood. Exp. Cell Res. 20, 613-616. Paris Conference (1972). Standardization in human cytogenetics. Birth Defects: Original Article Series 8, No. 7 , 1-43. Vogel, W., J. W. Siebers & H. Reinwein (1973). Partial trisomy 7q. Ann. Gknkt. 16, 277-280. Address: A. A1 Saadi William Beaumont Hospital Department of Anatomic Pathology 3601 West 13-Mile-Road Royal Oak, Michigan 98072 U.S.A.
Partial trisomy of the long arm of chromosome 7 A. AL SAADIAND HASSAN A. MOGHADAM Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak. Michigan, U S A . A baby with partial trisomy 7, 46, XY,t (5;7) (q35;q31) resulting from a familial translocation (5qf,7q -) is reported. The clinical abnormalities of this case closely resemble those of previously reported cases of partial trisomy 7. It is suggested that partial trisomy 7 may represent a clinical entity.
Received 5 June, accepted for publication 2 July 1975
Correct identification of chromosomal abnormalities by banding techniques is now a reality. Several examples of structural abnormality in the C-group have been precisely identified using the quinacrine and/or the Giemsa banding techniques. Partial trisomy of the long arm of chromosome 7 has been reported to result from translocations between chromosomes 7 and 14 (Alfi et al. 1973), 7 and 21 (Vogel et al. 1973). 7 and 12 (Carpentier et al. 1972), and 7 and 3 (Grace et al. 1973). In this report we present a case of partial trisomy 7 (7q3I + 7qter) resulting from a familial balanced translocation (5q+ ,7q-). The clinical findings are compared with those previously published in partial trisomy 7, and the clinical syndrome is discussed. Case Report
This male infant (111-5, Fig. 1) was born after full-term pregnancy to a gravida 1, para 0, 29-year-old white mother and a 29-year-old father. The baby was born elsewhere and was transferred to William
Beaumont Hospital at 8 h of age for further evaluation of malformations and breathing difficulty. The date of conception was uncertain because of irregular menstrual periods. The couple had been married for a little over 2 years, during which time no contraceptives were used. The pregnancy was uneventful; the mother took no drugs other than iron and vitamins and had no irradiation other than a set of dental roentgenograms. No history of miscarriages or malformed children was known in the mother’s family. The mother had had some vaginal spotting 2 weeks before delivery, but examination had revealed nothing unusual. The infant was delivered with the aid of forceps after a labor lasting 11 h. The baby’s weight was 2,156 g, length 48.5 cm and head circumference 36.8 cm. He was cyanotic and apneic, and intubation was necessary to maintain respiration. The Apgar values were 5 at 1 min and 6 at 10 min. Physical examination showed an abnormally shaped head, in which the parietal and occipitaI bones were more prominent than the frontal.
P A R T I A L T R I S O M Y OF T H E L O N G A R M O F C H R O M O S O M E 7
251
I
Fig. 1. Family pedigree. Empty circles or squares: normal karyotype. Half-shaded circles or squares: carriers of 5q+, 7q- translocations. Full square: partial trisomy 7q.
There were overriding of bones and a cephalohematoma in the left parietal area. The ears were malformed and low-set (Fig. 2). The bridge of the nose was flattened, and he had hypertelorism. Bilateral cleft palate and micrognathia were also present.
The sternum was unusually short. Heart tones were regular, and the cardiac rate was approximately 200/min. No pulmonary abnormalities were evident. The Moro reflex was positive, and the grasping reflex and sucking were poor. The fifth finger and the thumb were clenched over the other fingers. No simian creases were found. The baby had rocker-bottom feet. The baby was treated with Digoxin and Lasix because of heart failure and pulmonary edema. He died 20 h after birth. No additional gross malformations were encountered at postmortem examination, and microscopic examination of the major organs revealed no histologic abnormalities. Cytogenetlc Studies
Flg. 2. Proband shortly after death.
Chromosome preparations were done on peripheral leukocytes from the propositus (111-5) before his death and from all available relatives (Fig. 1) by using a modified technique of Moorehead et al. (1960). The slides were air-dried for a week, trypsinized with 0.025 % trypsin in Ca++- and Mg++-freeTyrode buffer for 20-30 s, and stained with Giemsa at pH 6.8 (Harleco 1 ml stock, 49 ml phosphate buffer). Each of the 30 examined cells of the propositus contained a long marker chromo-
252
SAADI AND MOGHADAM
Fig. 3. A representative karyotype of the proband showing the long chromosome 5 which consists of chromosome 5 and a portion of the long arm of chromosome 7.
some, which was subsequently identified as chromosome 5q+ (Fig. 3). The father (11-3), the paternal grandmother (I-l), and aunt (11-2) and a cousin (111-3) were all found to have the long chromosome 5q+ and a short chromosome 7 (7q-). The breakpoint on the long arm of chromosome 7 (Fig. 4) appears to have occurred in band 7q31 (Paris Conference, 1972). Since the father, the paternal grandmother, the aunt and the cousin each presumably carry a reciprocal translocation, another break must have taken place at the telomere of chromosome 5. However, this point cannot be confirmed, since most of the distal bands, 5q33 to 5q34, seem to be present in the rearranged chromosome 5q . The presumed breakpoint in chromosome 5 might have occurred, therefore, in the terminal band 5q35.
+
The baby had inherited the 5q+ chromosome and a normal no. 7 from his father and a normal no. 7 from his mother, and was therefore trisomic for the portion of the long arm of chromosome 7q31+7qter. The suggested designation of this translocation would be 46,XY,t (5;7) (q35;q31) in the short system and 46,XY,t (5;7) (5pter-t 5q35: :7q31+7qter; 7pter+7q31: :5q35+ 5qter) in the detailed system. Discussion
Partial trisomy for the long arm of chromosome 7 has been reported earlier (Carpentier et al. 1972, Alfi et al. 1973, Grace et al. 1973, Vogel et al. 1973). However, this is the first case known to us that resulted from a reciprocal translocation involving chromosomes 5q and 7q.
PARTIAL TRISOMY OF THE LONG ARM OF CHROMOSOME 7
Fig. 4. A representative kaiyotype of the paternal grandmother showing the 5q+, 7q-
All reported cases of partial 7q trisomy, including this one, seem to have had several common malformations. They include cleft palate, micrognathia, low-set and malformed ears, hypertelorism and large tongue, and are assumed to be the result of the excess chromosomal material. The extra material in this and at least two previously reported cases (Alfi et al. 1973, Vogel et al. 1973) appears to be a portion of the long arm of the chromosome 7q31+7qter. In two other reported cases of partial trisomy 7q (Carpentier et al. 1972, Grace et al. 1973) the clinical abnormalitites appear to be in close agreement with this case, although the excess chromosomal material was more in one case (Carpentier et al. 1972) and less in the other (Grace et al. 1973). Although most of the clinical abnormalities found in the partial 7q trisomy are also found in other chrornosoma1 anomalies, partial trisomy 7q may,
253
translocation
nevertheless, represent a defined clinical entity. It should be noted here that the mother of this baby failed to become pregnant for more than 2 years despite her desire to become pregnant. This can be explained by the possibility of early abortion(s) of partial trisomy 7 conceptus. This explanation can also be applied to the two spontaneous abortions, both in the first trimester, of the aunt who is a carrier of the translocation. Acknowledgments
We would like t o thank Dr. Jay Bernstein for his review and criticism of the manuscript, and we also thank Ms. M. Madercic and Ms. S. Charzan for their skillful technical assistance.
SAADl AND MOGHADAM
254 References
Alfi, 0. S., G. N. Donne11 & S. L. Kramer (1973). Partial trisomy of the long arm of chromosome, no. 7. 1. med. Genet. 10, 187189. Carpentier, S., M. 0. Rethore & J. Lejeune (1972). Trisomie partielle 7q par translocation familiale. t(7,12) (q22,q24). Ann. Ge'nPt. 15, 283-286. Grace, E., G. R. Sutherland, G. D. Start & A. D. Bain (1973). Partial trisomy of 7q resulting from a familial translocation. Ann. GinPt. 16, 51-54. Moorehead, P. S., P. C. Nowell, W. J. Mellman, D. M. Battips & D. A. Hungerford
(1960). Chromosome preparations of leukocytes cultured from human peripheral blood. Exp. Cell Res. 20, 613-616. Paris Conference (1972). Standardization in human cytogenetics. Birth Defects: Original Article Series 8, No. 7 , 1-43. Vogel, W., J. W. Siebers & H. Reinwein (1973). Partial trisomy 7q. Ann. Gknkt. 16, 277-280. Address: A. A1 Saadi William Beaumont Hospital Department of Anatomic Pathology 3601 West 13-Mile-Road Royal Oak, Michigan 98072 U.S.A.
