Hum. Genet. 35, 353--356 (1977) © by Springer-Verlag 1977
Clinical Case Reports
Partial Trisomy 10p and Familial Translocation t(7;10)(p22;p12) George Johnson 1, Ronald Bachman 2, Terry Roed 2, and Peggy Riddervold 2 Department of Biological Science, California State University, Hayward, CA 94 542, USA 2Department of Pediatrics, Kaiser Permanente Hospital, Oakland, California
Summary. A girl with partial trisomy for the short arm of chromosome 10(p 12--> pter) due to mal chromosome segregation in the father 46,XY,t(7;10)(p22;pi2) is described. The major abnormalities in this case are: mottled skin, mid-facial hypoplasia, low percentiles for weight, length, and head circumference, and club feet.
Introduction Schleiermacher et al. (1974) first reported the trisomy 10p syndrome. In their case a balanced 46,XX,t(7;10)(p22;pll) parent produced a daughter and a Son who were both affected. When the daughter was 11 years old and the son 9 years of age, their most distinctive concordant features were: mental deficiency, third percentile ranking for body size and head circumference, a high and bulky forehead, a broad nasal bridge, club feet, abnormalities of the teeth, and skeleton muscles which were hypoplastic and hypotonic. Both the mother and the maternal grandmother of these affected children were found to be balanced translocation heterozygotes with almost all of the short arm of one chromosome 10 attached to the short arm of one chromosome 7. The trisomy 10p syndrome developed in both of the children in connection with their receiving a normal chromosome 10 from each parent and the maternal 7 chromosome with the short arm of 10 attached. Without knowledge of the Schleiermacher et al. report, Hustinx et al. (1974) described the trisomy 10p syndrome in an immature female whose birth weight and length were 2120 g and 43 cm after 41 weeks of gestation. The child died of respiratory distress 48 h after birth. In addition to small body size, this newborn female had other malformations including: a broad nasal bridge, a unilateral hip dislocation, and club feet. The cytogenetic examination of her peripheral lymphocytes and skin fibroblasts revealed two normal 10 chromosomes and a chromosome 14 with virtually all of the short arm region of a 10 *
To whom offprint requests should be sent
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attached to it. Both the m o t h e r and y o u n g e r b r o t h e r of this 10p t r i s o m y child were b a l a n c e d t r a n s l o c a t i o n heterozygotes with the short a r m region of one c h r o m o s o m e 10 t r a n s l o c a t e d to the short a r m region of a 14. The c h r o m o s o m e s of the father a n d m a t e r n a l g r a n d p a r e n t s were n o r m a l . Grosse et al. (1975) f o u n d a case of partial 10p t r i s o m y in a boy a b o u t 5 years old. The patient was severely m e n t a l l y retarded, his weight, length, a n d head circumference were below the third percentile, his forehead was high and bulky, a n d the root of his nose was b r o a d a n d p r o m i n e n t . He was u n a b l e to walk and displayed severe hypotonia. W i t h the partial 10p t r i s o m y s y m p t o m s in this 5-year-old boy so closely corres p o n d i n g with the two earlier reports of complete 10p trisomy, it is n o t surprizing that the s u p e r n u m e r a r y a m o u n t of the short a r m of 10 is nearly the same in all three cases. The extra material involved in the patients of Schleiermacher et al. a n d H u s t i n x et al. was between b a n d 10pl 1 a n d 10pter, a n d j u d g i n g from the c h r o m o s o m e s s h o w n in the report of Grosse et al., the extra material present in the 5-year-old b o y was the region between b a n d 10pl2 a n d 10pter. Grosse et al. f o u n d that the patient's father was a b a l a n c e d t r a n s l o c a t i o n heterozygote with most of the short a r m of one 10 translocated to the long a r m of one 7. The p a t e r n a l g r a n d p a r e n t s were n o t available for study.
Case Report Early fetal development was slow, even though the estriol levels were normal, but later on fetal growth improved and on March 18, 1976, a 2998 g female was born 10 days after her due date. At the time of birth several abnormalities were apparent including a general mottling of the skin, possible microophthalmia, blue sclera, an antimongoloid slant to the eyes, clinodactyly, bifid uvula, and a soft 2 cm skin lesion at the base of the spine. At birth the patient had a weak cry and poor color which were treated with oxygen. She was a poor feeder requiring tube feedings during the first week. Upon re-examination of the patient at 6 weeks of age additional findings were noted. Although the patient's eyes were of normal size, their recession beneath a buIky forehead had given the earlier impression of microophthalmia. The patient had mid-facial hypoplasia with a scooped out base of the nose (Fig. 1). The nose was upturned. The weight and head circumference values were below the third percentile, and the body length was equal to the tenth percentile. A hip click was noticed upon abduction of the right hip, and the right foot was clubbed. The mother and father are unrelated and are 30 and 28 years old, respectively. The patient is their first child, although a year earlier the couple had a pregnancy end in a miscarriage at 11 weeks.
Cytogenetic Findings Blood was t a k e n from the patient shortly after birth to establish a peripheral l y m p h o c y t e culture for c h r o m o s o m e analysis. A 7p+ c h r o m o s o m e was observed in each of the 24 complete cells which were analysed (Fig. 1). This finding p r o m p t e d a cytogenetic study of parental lymphocytes. Based on 21 complete cells, the m o t h e r of the p a t i e n t was d e t e r m i n e d to be 46,XX. The father was j u d g e d to be a b a l a n c e d t r a n s l o c a t i o n heterozygote in each of the 27 cells studied. Most of the short a r m of one c h r o m o s o m e 10 was obviously translocated to the short a r m of a 7, b u t we could neither rule out n o r verify if a small distal p o r t i o n
Partial Trisomy 10p
355
Fig. 1. A partial 10p trisomy child and two examples of the involved chromosomes
Fig. 2. Two partial karyotypes from paternal cells described as: 46,XY, t(7;10)(p22;p12) of the short arm of a 7 had reciprocally become attached to the 10p-chromosome. Assuming the father to be a reciprocal translocation heterozygote, the detailed description of his karyotype would be: 46,XY, t(7;10)(Tqter-~Tp22:: 10p 12 ~ 10pter; 10qter -~l 0p 12 : : 7p22 ~Tpter). A partial karyotype showing the father's translocation is shown in Figure 2. We have not been able to study other relatives of the patient's father.
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Discussion Neither dolicocephaly nor severe respiratory distress as reported in other cases of 10p trisomy seem to be constant features of this syndrome. The pattern of abnormalities typically associated with the 10p trisomy syndrome appears to be: mental retardation, third percentile values for height, weight, and head circumference, a bulky forehead, broad nasal bridge, club feet, and hypotonia of skeleton muscles. In the cases reported to date, either the patients have had three doses of virtually all of the short arm of chromosome 10 or just one proximal band less than this amount. Perhaps some of these abnormalities will not develop in cases yet to be reported in which a smaller amount of the short arm of 10 will be supernumerary.
References Grosse, K., Schwanitz, G., Singer, H., Wieezorek, V.: Partial trisomy 10p. Humangenetik 29, 141 144 (1975) Hustinx, T., ter Haar, B., Scheres, J., Rutten, F.: Trisomy for the short arm of chromosome No. 10. Clinical Genetics 6, 408~415 (1974) Schleiermacher, E., Schliebitz, U., Steffens, C.: Brother and sister with trisomy 10p: A new syndrome. Humangenetik 23, 163--172 (1974) Received September 30, 1976
Clinical Case Reports
Partial Trisomy 10p and Familial Translocation t(7;10)(p22;p12) George Johnson 1, Ronald Bachman 2, Terry Roed 2, and Peggy Riddervold 2 Department of Biological Science, California State University, Hayward, CA 94 542, USA 2Department of Pediatrics, Kaiser Permanente Hospital, Oakland, California
Summary. A girl with partial trisomy for the short arm of chromosome 10(p 12--> pter) due to mal chromosome segregation in the father 46,XY,t(7;10)(p22;pi2) is described. The major abnormalities in this case are: mottled skin, mid-facial hypoplasia, low percentiles for weight, length, and head circumference, and club feet.
Introduction Schleiermacher et al. (1974) first reported the trisomy 10p syndrome. In their case a balanced 46,XX,t(7;10)(p22;pll) parent produced a daughter and a Son who were both affected. When the daughter was 11 years old and the son 9 years of age, their most distinctive concordant features were: mental deficiency, third percentile ranking for body size and head circumference, a high and bulky forehead, a broad nasal bridge, club feet, abnormalities of the teeth, and skeleton muscles which were hypoplastic and hypotonic. Both the mother and the maternal grandmother of these affected children were found to be balanced translocation heterozygotes with almost all of the short arm of one chromosome 10 attached to the short arm of one chromosome 7. The trisomy 10p syndrome developed in both of the children in connection with their receiving a normal chromosome 10 from each parent and the maternal 7 chromosome with the short arm of 10 attached. Without knowledge of the Schleiermacher et al. report, Hustinx et al. (1974) described the trisomy 10p syndrome in an immature female whose birth weight and length were 2120 g and 43 cm after 41 weeks of gestation. The child died of respiratory distress 48 h after birth. In addition to small body size, this newborn female had other malformations including: a broad nasal bridge, a unilateral hip dislocation, and club feet. The cytogenetic examination of her peripheral lymphocytes and skin fibroblasts revealed two normal 10 chromosomes and a chromosome 14 with virtually all of the short arm region of a 10 *
To whom offprint requests should be sent
354
G. Johnson et al.
attached to it. Both the m o t h e r and y o u n g e r b r o t h e r of this 10p t r i s o m y child were b a l a n c e d t r a n s l o c a t i o n heterozygotes with the short a r m region of one c h r o m o s o m e 10 t r a n s l o c a t e d to the short a r m region of a 14. The c h r o m o s o m e s of the father a n d m a t e r n a l g r a n d p a r e n t s were n o r m a l . Grosse et al. (1975) f o u n d a case of partial 10p t r i s o m y in a boy a b o u t 5 years old. The patient was severely m e n t a l l y retarded, his weight, length, a n d head circumference were below the third percentile, his forehead was high and bulky, a n d the root of his nose was b r o a d a n d p r o m i n e n t . He was u n a b l e to walk and displayed severe hypotonia. W i t h the partial 10p t r i s o m y s y m p t o m s in this 5-year-old boy so closely corres p o n d i n g with the two earlier reports of complete 10p trisomy, it is n o t surprizing that the s u p e r n u m e r a r y a m o u n t of the short a r m of 10 is nearly the same in all three cases. The extra material involved in the patients of Schleiermacher et al. a n d H u s t i n x et al. was between b a n d 10pl 1 a n d 10pter, a n d j u d g i n g from the c h r o m o s o m e s s h o w n in the report of Grosse et al., the extra material present in the 5-year-old b o y was the region between b a n d 10pl2 a n d 10pter. Grosse et al. f o u n d that the patient's father was a b a l a n c e d t r a n s l o c a t i o n heterozygote with most of the short a r m of one 10 translocated to the long a r m of one 7. The p a t e r n a l g r a n d p a r e n t s were n o t available for study.
Case Report Early fetal development was slow, even though the estriol levels were normal, but later on fetal growth improved and on March 18, 1976, a 2998 g female was born 10 days after her due date. At the time of birth several abnormalities were apparent including a general mottling of the skin, possible microophthalmia, blue sclera, an antimongoloid slant to the eyes, clinodactyly, bifid uvula, and a soft 2 cm skin lesion at the base of the spine. At birth the patient had a weak cry and poor color which were treated with oxygen. She was a poor feeder requiring tube feedings during the first week. Upon re-examination of the patient at 6 weeks of age additional findings were noted. Although the patient's eyes were of normal size, their recession beneath a buIky forehead had given the earlier impression of microophthalmia. The patient had mid-facial hypoplasia with a scooped out base of the nose (Fig. 1). The nose was upturned. The weight and head circumference values were below the third percentile, and the body length was equal to the tenth percentile. A hip click was noticed upon abduction of the right hip, and the right foot was clubbed. The mother and father are unrelated and are 30 and 28 years old, respectively. The patient is their first child, although a year earlier the couple had a pregnancy end in a miscarriage at 11 weeks.
Cytogenetic Findings Blood was t a k e n from the patient shortly after birth to establish a peripheral l y m p h o c y t e culture for c h r o m o s o m e analysis. A 7p+ c h r o m o s o m e was observed in each of the 24 complete cells which were analysed (Fig. 1). This finding p r o m p t e d a cytogenetic study of parental lymphocytes. Based on 21 complete cells, the m o t h e r of the p a t i e n t was d e t e r m i n e d to be 46,XX. The father was j u d g e d to be a b a l a n c e d t r a n s l o c a t i o n heterozygote in each of the 27 cells studied. Most of the short a r m of one c h r o m o s o m e 10 was obviously translocated to the short a r m of a 7, b u t we could neither rule out n o r verify if a small distal p o r t i o n
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355
Fig. 1. A partial 10p trisomy child and two examples of the involved chromosomes
Fig. 2. Two partial karyotypes from paternal cells described as: 46,XY, t(7;10)(p22;p12) of the short arm of a 7 had reciprocally become attached to the 10p-chromosome. Assuming the father to be a reciprocal translocation heterozygote, the detailed description of his karyotype would be: 46,XY, t(7;10)(Tqter-~Tp22:: 10p 12 ~ 10pter; 10qter -~l 0p 12 : : 7p22 ~Tpter). A partial karyotype showing the father's translocation is shown in Figure 2. We have not been able to study other relatives of the patient's father.
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Discussion Neither dolicocephaly nor severe respiratory distress as reported in other cases of 10p trisomy seem to be constant features of this syndrome. The pattern of abnormalities typically associated with the 10p trisomy syndrome appears to be: mental retardation, third percentile values for height, weight, and head circumference, a bulky forehead, broad nasal bridge, club feet, and hypotonia of skeleton muscles. In the cases reported to date, either the patients have had three doses of virtually all of the short arm of chromosome 10 or just one proximal band less than this amount. Perhaps some of these abnormalities will not develop in cases yet to be reported in which a smaller amount of the short arm of 10 will be supernumerary.
References Grosse, K., Schwanitz, G., Singer, H., Wieezorek, V.: Partial trisomy 10p. Humangenetik 29, 141 144 (1975) Hustinx, T., ter Haar, B., Scheres, J., Rutten, F.: Trisomy for the short arm of chromosome No. 10. Clinical Genetics 6, 408~415 (1974) Schleiermacher, E., Schliebitz, U., Steffens, C.: Brother and sister with trisomy 10p: A new syndrome. Humangenetik 23, 163--172 (1974) Received September 30, 1976
