EuropeanJournal of
Europ. J. Pediat. 124, 167--171 (1977)
Pediatrics 9 by Springer-Verlag 1977
Hemihypotrophy in a Girl with a Translocation t(13q;7p)* F. A. M a r g a l l o l, L. C. W e r n e c k 2, R . F . P i l o t t o 1, a n d J. M. O p i t z 3,4 l Departments of Genetics and 2Medicine, Federal University of Parang, Brazil; 3Wisconsin Clinical Genetics Center of the Department of Medical Genetics and 4 Department of Pediatrics, University of Winconsin Center for Health Sciences and Medical School, Madison, Wisconsin 53 706, USA
Abstract. A 10 y e a r old girl with a m e n t a l age o f 7 - - 8 years, n o r m a l height a n d h e a d c i r c u m f e r e n c e a n d several m i n o r a n o m a l i e s h a d h e m i a s y m m e t r y o f the entire b o d y , the left side being u n i f o r m l y smaller t h a n the right. T h e s m a l l e r side was c o n s i d e r e d the a b n o r m a l side a n d her c o n d i t i o n i n t e r p r e t e d as hemih y p o t r o p h y on the basis o f a c h r o m o s o m e a b n o r m a l i t y which involved m o s a i c i s m , with l y m p h o c y t e s s h o w i n g a b a l a n c e d b u t very u n e q u a l transl o c a t i o n o f m o s t of 13q t r a n s f e r r e d to 7p a n d b o t h t r a n s l o c a t i o n c h r o m o somes being present, a n d all e x a m i n e d f i b r o b l a s t s l a c k i n g the small transl o c a t i o n c h r o m o s o m e a n d hence being m o n o s o m i c for 13p, p r o x i m a l p a r t of 13q a n d a t e r m i n a l p o r t i o n o f 7p. K e y w o r d s : H e m i a s y m m e t r y - H e m i h y p o t r o p h y - de novo t r a n s l o c a t i o n (46,XX,t[13q;7p]) - M o s a i c i s m - B a l a n c e d cell line - U n b a l a n c e d cell line B o r d e r l i n e intelligence - M i n o r a n o m a l i e s .
Introduction In m a n y p a t i e n t s with subtle a s y m m e t r y o f size of the two halves o f the b o d y it is n o t p o s s i b l e to decide w h e t h e r the larger or smaller side is the a b n o r m a l side a n d w h e t h e r the p a t i e n t has h e m i h y p e r t r o p h y o r h e m i h y p o t r o p h y ; s o m e prefer the t e r m a s y m m e t r y in such cases ( F e r r i e r et al., 1964). W e t h i n k the p r e s e n t p a t i e n t p r o b a b l y has h e m i h y p o t r o p h y a n d we s h o u l d like to present evidence for it a n d the p r o b a b l e cause o f the c o n d i t i o n . * Supported by grants of the National Council of the Scientific and Technologic Development (CNPq/PIG) - - Brazil, and by DHEW/USPHS Grant GM20 130 from the National Institute of General Medical Sciences. Contributed, in part, as paper number 1962 from the University of Wisconsin Genetics Laboratory Address for offprint requests: Professor F. A. Margallo, Genetics Department, Caixa Postal AA, 80 000 Curitiba, Pr., Brazil
Fig. l a and b. Note smaller size of left half of body, pelvic and shoulder tilt to the left
Fig. 2a and b. Note smaller size of left half of face and tongue; epicanthic folds more pronounced on left than on right, left eye apparently "lower" than right, and mucosal portion of left half of upper lip smaller than the right half
Hemihypotrophy and (13q;7p) Translocation
1
2
3
XX XR
h tl D
XX
169
16
XX
*x
F
17
18
~
~n G
Fig. 3. Tracing of Giemsa stained lymphocyte karyotype with both translocation chromosomes (*); note only 5D and 15D chromosomes; the large translocation chromosome in 2-like, the smaller is smaller than a G and is satellited. Karyotype: 46.XX,t(13q;7p)
Clinical Report and Cytogenetic Studies This ten-year-old white girl was born by Cesarean section for placenta previa after a 34-week pregnancy. The infant was not cyanotic nor slow to cry, She was the last in a sibship of three including in chronologic order a sister, brother and sister, all sibs being normal. Her mother had no spontaneous abortions and no other abnormalities are known in the family. Her development was retarded: she held her head up at 7 months, sat, walked and talked, respectively, at 1l/z, 28/12 and 3 years. Examination at 2Y2 years showed cranio-facial asymmetry with the left bemicranium being smaller than the right. A Babinski sign was present on the right. Muscle strength was reduced with the right side being weaker or more hypotonic than the left. At the present time she is of normal height and weight and has a normal head circumference; she has a mental age of 7--8 years, a depressed nasal bridge, highly arched palate and asymmetry of the entire body including the tongue, with the left side being slightly smaller than the right (Fig. 1, 2). Her muscle strength is reduced in all four limbs, and the muscle mass on the left appears to be smaller than that on the right. Tone and coordination are normal. She has normal dermatoglyphics except for 10 arches on fingertips and absence of both c triradii. Radiographic studies show bony asymmetry with the long bones of the left limbs being shorter than those on the right. In lymphocytes she had a reciprocal 13/7 translocation (46,XX,t[13q;7p]) with the majority of 13q translocated to the tip of 7p and the small translocation chromosome being present in all cells examined (Fig. 3); however, in fibroblasts this small chromosome was invariably absent (Fig. 4a, b). Thus, this patient is a mosaic with a balanced and an unbalanced cell line, the latter lacking 13p (not a deleterious defect), and the proximal portion of 13q and presumably a terminal portion of 7p (Fig. 5). Both parents had apparently normal chromosomes.
170
F.A. Marqallo et al.
Fig. 4. a Trypsin-Giemsa banded fibroblast chromosome preparations from both sides of the body show only 45 chromosomes - - the large, 2-like translocation chromosome, 5D and 15C chromosomes. The breaks occurred near the centromere of 13q and near the tip of 7p. b The 13, translocation and 7 chromosomes from four cells. Breakage notation: 46,XX,t(13;7)(q12;p22). Chromosome preparation and G banding by Ms.Diane Biehrke; karyotypes by Dr. B. R. Elejalde
q
q,r--.- 13.~.r-~p
o~ c~
Fig. 5. Tracing of photometric curves prepared by Dr. B. R. Elejalde from the two partial karyotypes of Fig. 4b. A represents the curve due to the short arm of 13; B is the curve due to the terminal segment of 7p. Region A is certainly absent in the large 13/7 translocation chromosome, and at least a small part of region B must also be absent. Thus, the large wave indicated by the asterisk in the translocation chromosome is surprising and may represent a new band due to interaction between terminal 7p and proximal 13q chromatin. The staining characteristics of this band are under further investigation
Hemihypotrophy and (13q;7p) Translocation
171
Discussion A s y m m e t r y o f b o d y size a s s o c i a t e d with c h r o m o s o m e a b n o r m a l i t i e s has been r e p o r t e d b y a n u m b e r o f a u t h o r s (Ellis et al., 1963; F e r r i e r et al., 1964; Br0gger et al., 1964; R i n g r o s e et al., 1965). T h e c h r o m o s o m e a b n o r m a l i t y was different in each case. Because o f her otherwise n o r m a l g r o w t h we p o s t u l a t e t h a t our p a t i e n t ' s small side is the a b n o r m a l side a n d t h a t she has h e m i h y p o t r o p h y . Since she has an u n b a l a n c e d cell line we p o s t u l a t e that her h e m i h y p o t r o p h y represents the deleterious effect on g r o w t h u s u a l l y seen in individuals with gross a u t o s o m a l a b n o r m a l i t i e s . O t h e r m i n o r a n o m a l i e s a n d her b o r d e r l i n e intelligence are, in this case, also i n t e r p r e t e d as deleterious effects d u r i n g d e v e l o p m e n t o f the u n b a l a n c e d cell line.
Acknowledgements. We are most grateful to the late Prof. K. Patau of the University of Wisconsin for the identification of the chromosomes involved in the translocation by means of the fluorescence technique; to Dr. R. I. DeMars of the University of Wisconsin for culturing fibroblasts from a skin biopsy and for providing photomicrographs of the fibroblast chromosomes, and to Dr. B. R. Elejalde Salazar of the University of Wisconsin for preparing the karyotypes of the fibroblast chromosomes and for performing the photometric studies of the normal and translocation chromosomes.
References Bragger, A., van der Hagen, C. B., StOren, A.: Mosaieism involving two karyotypes with 45 chromosomes and a new autosomaI translocation in a girl with mental defect, asymmetry, congenital heart disease and other malformations. Aeta paediat. (Uppsala)Suppl. 159, 44 (1964) Ellis, J. R., Marshall, R., Normand, I. C. S., Penrose, L. S.: A girl with triploid cells. Nature 198, 411 (1963) Ferrier, P., Ferrier, S., Stalder, G., Btihler, E., Bamatter, F., Klein, D.: Congenital asymmetry associated with a diploid-triploid mosaicism and large satellites. Lancet 19641, 80--82 Ringrose, R. E., Jabbour, J. T., Keele, D. K.: Hemihypertrophy. Pediatrics 36(3)/1, 434~448 (1965)
Received September 8, 1976
Europ. J. Pediat. 124, 167--171 (1977)
Pediatrics 9 by Springer-Verlag 1977
Hemihypotrophy in a Girl with a Translocation t(13q;7p)* F. A. M a r g a l l o l, L. C. W e r n e c k 2, R . F . P i l o t t o 1, a n d J. M. O p i t z 3,4 l Departments of Genetics and 2Medicine, Federal University of Parang, Brazil; 3Wisconsin Clinical Genetics Center of the Department of Medical Genetics and 4 Department of Pediatrics, University of Winconsin Center for Health Sciences and Medical School, Madison, Wisconsin 53 706, USA
Abstract. A 10 y e a r old girl with a m e n t a l age o f 7 - - 8 years, n o r m a l height a n d h e a d c i r c u m f e r e n c e a n d several m i n o r a n o m a l i e s h a d h e m i a s y m m e t r y o f the entire b o d y , the left side being u n i f o r m l y smaller t h a n the right. T h e s m a l l e r side was c o n s i d e r e d the a b n o r m a l side a n d her c o n d i t i o n i n t e r p r e t e d as hemih y p o t r o p h y on the basis o f a c h r o m o s o m e a b n o r m a l i t y which involved m o s a i c i s m , with l y m p h o c y t e s s h o w i n g a b a l a n c e d b u t very u n e q u a l transl o c a t i o n o f m o s t of 13q t r a n s f e r r e d to 7p a n d b o t h t r a n s l o c a t i o n c h r o m o somes being present, a n d all e x a m i n e d f i b r o b l a s t s l a c k i n g the small transl o c a t i o n c h r o m o s o m e a n d hence being m o n o s o m i c for 13p, p r o x i m a l p a r t of 13q a n d a t e r m i n a l p o r t i o n o f 7p. K e y w o r d s : H e m i a s y m m e t r y - H e m i h y p o t r o p h y - de novo t r a n s l o c a t i o n (46,XX,t[13q;7p]) - M o s a i c i s m - B a l a n c e d cell line - U n b a l a n c e d cell line B o r d e r l i n e intelligence - M i n o r a n o m a l i e s .
Introduction In m a n y p a t i e n t s with subtle a s y m m e t r y o f size of the two halves o f the b o d y it is n o t p o s s i b l e to decide w h e t h e r the larger or smaller side is the a b n o r m a l side a n d w h e t h e r the p a t i e n t has h e m i h y p e r t r o p h y o r h e m i h y p o t r o p h y ; s o m e prefer the t e r m a s y m m e t r y in such cases ( F e r r i e r et al., 1964). W e t h i n k the p r e s e n t p a t i e n t p r o b a b l y has h e m i h y p o t r o p h y a n d we s h o u l d like to present evidence for it a n d the p r o b a b l e cause o f the c o n d i t i o n . * Supported by grants of the National Council of the Scientific and Technologic Development (CNPq/PIG) - - Brazil, and by DHEW/USPHS Grant GM20 130 from the National Institute of General Medical Sciences. Contributed, in part, as paper number 1962 from the University of Wisconsin Genetics Laboratory Address for offprint requests: Professor F. A. Margallo, Genetics Department, Caixa Postal AA, 80 000 Curitiba, Pr., Brazil
Fig. l a and b. Note smaller size of left half of body, pelvic and shoulder tilt to the left
Fig. 2a and b. Note smaller size of left half of face and tongue; epicanthic folds more pronounced on left than on right, left eye apparently "lower" than right, and mucosal portion of left half of upper lip smaller than the right half
Hemihypotrophy and (13q;7p) Translocation
1
2
3
XX XR
h tl D
XX
169
16
XX
*x
F
17
18
~
~n G
Fig. 3. Tracing of Giemsa stained lymphocyte karyotype with both translocation chromosomes (*); note only 5D and 15D chromosomes; the large translocation chromosome in 2-like, the smaller is smaller than a G and is satellited. Karyotype: 46.XX,t(13q;7p)
Clinical Report and Cytogenetic Studies This ten-year-old white girl was born by Cesarean section for placenta previa after a 34-week pregnancy. The infant was not cyanotic nor slow to cry, She was the last in a sibship of three including in chronologic order a sister, brother and sister, all sibs being normal. Her mother had no spontaneous abortions and no other abnormalities are known in the family. Her development was retarded: she held her head up at 7 months, sat, walked and talked, respectively, at 1l/z, 28/12 and 3 years. Examination at 2Y2 years showed cranio-facial asymmetry with the left bemicranium being smaller than the right. A Babinski sign was present on the right. Muscle strength was reduced with the right side being weaker or more hypotonic than the left. At the present time she is of normal height and weight and has a normal head circumference; she has a mental age of 7--8 years, a depressed nasal bridge, highly arched palate and asymmetry of the entire body including the tongue, with the left side being slightly smaller than the right (Fig. 1, 2). Her muscle strength is reduced in all four limbs, and the muscle mass on the left appears to be smaller than that on the right. Tone and coordination are normal. She has normal dermatoglyphics except for 10 arches on fingertips and absence of both c triradii. Radiographic studies show bony asymmetry with the long bones of the left limbs being shorter than those on the right. In lymphocytes she had a reciprocal 13/7 translocation (46,XX,t[13q;7p]) with the majority of 13q translocated to the tip of 7p and the small translocation chromosome being present in all cells examined (Fig. 3); however, in fibroblasts this small chromosome was invariably absent (Fig. 4a, b). Thus, this patient is a mosaic with a balanced and an unbalanced cell line, the latter lacking 13p (not a deleterious defect), and the proximal portion of 13q and presumably a terminal portion of 7p (Fig. 5). Both parents had apparently normal chromosomes.
170
F.A. Marqallo et al.
Fig. 4. a Trypsin-Giemsa banded fibroblast chromosome preparations from both sides of the body show only 45 chromosomes - - the large, 2-like translocation chromosome, 5D and 15C chromosomes. The breaks occurred near the centromere of 13q and near the tip of 7p. b The 13, translocation and 7 chromosomes from four cells. Breakage notation: 46,XX,t(13;7)(q12;p22). Chromosome preparation and G banding by Ms.Diane Biehrke; karyotypes by Dr. B. R. Elejalde
q
q,r--.- 13.~.r-~p
o~ c~
Fig. 5. Tracing of photometric curves prepared by Dr. B. R. Elejalde from the two partial karyotypes of Fig. 4b. A represents the curve due to the short arm of 13; B is the curve due to the terminal segment of 7p. Region A is certainly absent in the large 13/7 translocation chromosome, and at least a small part of region B must also be absent. Thus, the large wave indicated by the asterisk in the translocation chromosome is surprising and may represent a new band due to interaction between terminal 7p and proximal 13q chromatin. The staining characteristics of this band are under further investigation
Hemihypotrophy and (13q;7p) Translocation
171
Discussion A s y m m e t r y o f b o d y size a s s o c i a t e d with c h r o m o s o m e a b n o r m a l i t i e s has been r e p o r t e d b y a n u m b e r o f a u t h o r s (Ellis et al., 1963; F e r r i e r et al., 1964; Br0gger et al., 1964; R i n g r o s e et al., 1965). T h e c h r o m o s o m e a b n o r m a l i t y was different in each case. Because o f her otherwise n o r m a l g r o w t h we p o s t u l a t e t h a t our p a t i e n t ' s small side is the a b n o r m a l side a n d t h a t she has h e m i h y p o t r o p h y . Since she has an u n b a l a n c e d cell line we p o s t u l a t e that her h e m i h y p o t r o p h y represents the deleterious effect on g r o w t h u s u a l l y seen in individuals with gross a u t o s o m a l a b n o r m a l i t i e s . O t h e r m i n o r a n o m a l i e s a n d her b o r d e r l i n e intelligence are, in this case, also i n t e r p r e t e d as deleterious effects d u r i n g d e v e l o p m e n t o f the u n b a l a n c e d cell line.
Acknowledgements. We are most grateful to the late Prof. K. Patau of the University of Wisconsin for the identification of the chromosomes involved in the translocation by means of the fluorescence technique; to Dr. R. I. DeMars of the University of Wisconsin for culturing fibroblasts from a skin biopsy and for providing photomicrographs of the fibroblast chromosomes, and to Dr. B. R. Elejalde Salazar of the University of Wisconsin for preparing the karyotypes of the fibroblast chromosomes and for performing the photometric studies of the normal and translocation chromosomes.
References Bragger, A., van der Hagen, C. B., StOren, A.: Mosaieism involving two karyotypes with 45 chromosomes and a new autosomaI translocation in a girl with mental defect, asymmetry, congenital heart disease and other malformations. Aeta paediat. (Uppsala)Suppl. 159, 44 (1964) Ellis, J. R., Marshall, R., Normand, I. C. S., Penrose, L. S.: A girl with triploid cells. Nature 198, 411 (1963) Ferrier, P., Ferrier, S., Stalder, G., Btihler, E., Bamatter, F., Klein, D.: Congenital asymmetry associated with a diploid-triploid mosaicism and large satellites. Lancet 19641, 80--82 Ringrose, R. E., Jabbour, J. T., Keele, D. K.: Hemihypertrophy. Pediatrics 36(3)/1, 434~448 (1965)
Received September 8, 1976
