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TRISOMY-E-LIKE SYNDROME
696 noted rib abnormalities in all of them 1: the first ribs were absent in 1, and strongly hypoplastic in 6 others. The twelfth rib was absent in 3 of the children, 1 of whom also lacked eleventh ribs. We also examined pelvic radiographs in the 8 infants with D1 trisomy, and in 7 we noted acetabular angles which were more than two standard deviations below the mean for normal infants of the same sex.2 The iliac angles were within normal limits. This is in contrast to Down’s syndrome (trisomy 21), in which both acetabular and iliac angles tend to be low. 34
Partial phenotypic overlap between different types of autosomal imbalance thus appears to be present radiographically, as well as clinically, celluJarly,5 and biochemically. 61 Department of Pediatrics and Division of Experimental Medicine, University of Oregon Medical School, Portland, Oregon 97201, U.S.A.
FREDERICK HECHT.
TRISOMY-E-LIKE SYNDROME SIR,-Smith et al. 8 suggested that each autosomal trisomy syndrome might be clinically recognisable by a specific pattern of congenital anomalies. " Somewhat more frequent than these trisomics, who are extremely rare, are patients who display various combinations of the anomalies of either syndrome, but have 46 chromosomes."9 Many of these cases are best interpreted as a result of partial trisomy,
The patient had an odd-shaped head, with wide occipitoparietal and narrow frontal diameters, and a peculiar facies characterised by bilateral ptosis with antimongoloid palpebral fissures, a broad flat nasal bridge, low-set large ears, a small receding mandible, and a small mouth with a cleft palate. There was polydactyly of the hands, and polydactyly with syndactyly of the feet. There was retroflexibility of the thumbs, and general spasticity. The external genitalia were those of a hypospadiac boy. A grade-n rough systolic murmur was audible to the left of the sternum with maximal intensity over the 2nd and 3rd intercostal spaces. Chest X-rays revealed a globular, generally hypertrophied heart with increased pulmonary vascularity. Measurements of the serum concentrations of CO2, chloride, sodium, potassium, calcium, phosphorus, and total protein did not yield any significant changes. The respiratory infection, which was complicated by enterocolitis and purulent otitis media, did not improve despite intensive antimicrobial treatment, and the child died suddenly after a short haematemesis after 5 weeks in hospital. At necropsy both lungs showed patchy areas of collapse. The ductus arteriosus was patent. Both ventricles of the heart, especially the left, were hypertrophied. The liver showed fatty degeneration, the left kidney was displaced downward, and the testicles were in the abdominal cavity. The brain was slightly underweight (300 g.). On histological examination, the heart showed endocardial fibroelastosis ; the brain appeared immature. There was persistence of the foetal granular layers in the cerebellum, and there were many patchy areas of undifferentiated glial tissue surrounding the ventricular system. Many neurons were necrotic or atrophic. There was striking proliferation of glial tissue, and the cells of the substantia nigra showed sclerotic changes. The chromosomes, which were counted in 15 cells from short-term leucocyte culture, all contained 46 chromosomes. 5 cells were analysed in detail-they showed apparently normal karyotypes. 3rd Pediatric Clinic, WANDA SZOTOWA Medical Academy, BARBARA KOWALEWSKA. Dzialdowska 1, Warsaw.
INTRINSIC-FACTOR ASSAY RESULTS SIR,-Dr. Ardeman and Dr. Chanarin (Aug. 14) state that the unit of intrinsic factor described by them in 19651 is the same as the one they described in 1963.2 Yet in 1963 they stated: It is suggested that one unit of intrinsic factor should be that amount that will promote the uptake of 1 (Jtmg. of 60CO- Vitamin B12 to normal serum ",2 and in 1965: This is expressed in units, one unit being the specific binding (i.e., to intrinsic factor) of one ung. of vitamin B12-"1 As we have written (Aug. 7), this change in their definition of a unit of intrinsic factor indicates that they have dropped their prior hypothesis1 on the mechanism of action of the charcoal assay, and have adopted the hypothesis we presented.3 Thus, their unit remains unchanged in that the number of jjtmg. of B12 is unchanged, but the definition of the unit is changed from intrinsic-factor-mediated uptake by serum to uptake by intrinsic "
"
although the structural alterations of the recipient chromosome are usually too small to be detected microscopically. We describe here a male infant with all the clinical characteristics of the trisomy-E-like syndrome, but with normal chromosome constitution. Unfortunately his chromosomes were examined from too few cells to test the possibility of mosaicism or
partial trisomy. The patient (see accompanying figure) was first seen by us at 5 weeks of age. His mother and father, aged 24 and 29 respectively, and his only sister, aged 3, were all healthy. The infant was delivered at term, the birth-weight being 2000 g., and the length 44 cm. He was admitted to our clinic because of respiratory infection with swallowing difficulties from birth. ,
Hecht, F., Loop, J. W., Graham, C. B. J. Pediat. (in the press). Ryder, C. T., Mellin, G. W., Caffey, J. Clin. Orthop. 1962, 22, 7. Caffey, J., Ross, S. Pediatrics, 1956, 17, 642. Caffey, J., Ross, S. J. Roentgenol. 1958, 80, 458. Hecht, F., Huehns, E. R., Lutzner, M. J. Pediat. 1964, 65, 1089. Huehns, E. R., Hecht, F., Keil, J. V., Motulsky, A. G. Proc. natn. Acad. Sci. U.S.A. 1964, 51, 89. 7. Weinstein, E. D., Rucknagel, D. L., Shaw, M. W. Am. J. hum. Genet. 1965, 17, 443. 8. Smith, D. W., Patau, K., Therman, E. Am. J. Dis. Child. 1961, 102, 1. 2. 3. 4. 5. 6.
587. 9.
Smith,
D.
W., Patau, K., Therman,
E.
Lancet, 1961, ii, 211.
factor. The other point made by Dr. Ardeman and Dr. Chanarin (Aug. 14) is that we fail to make allowance for a serum blank in the intrinsic-factor assay technique that we favour4 and that " this may on occasion introduce grave error, particularly in gastric-juice samples with low intrinsic-factor concentration ". This statement is not correct since our intrinsic-factor assay results are expressed thus: " The unsaturated B12 binding capacity of this gastric juice is x pg. of B12 per ml., of which y pg. are due to intrinsic factor."4 In order to arrive at y, obviously the relatively small unsaturated B12 binding capacity of the antibody must be added to the relatively large amount of reduction of B12 binding to gastric juice brought about by the Ardeman, S., Chanarin, I. Br. J. Hœmat. 1965, 11, 305. Ardeman, S., Chanarin, I. Lancet, 1963, ii, 1350. Herbert, V., Gottlieb, C., Lau, K.-S., Wasserman, L. R. ibid. 1964, ii, 1017. 4. Gottlieb, C., Lau, K.-S., Wasserman, L. R., Herbert, V. Blood, 1965, 25, 875. 1. 2. 3.
Partial phenotypic overlap between different types of autosomal imbalance thus appears to be present radiographically, as well as clinically, celluJarly,5 and biochemically. 61 Department of Pediatrics and Division of Experimental Medicine, University of Oregon Medical School, Portland, Oregon 97201, U.S.A.
FREDERICK HECHT.
TRISOMY-E-LIKE SYNDROME SIR,-Smith et al. 8 suggested that each autosomal trisomy syndrome might be clinically recognisable by a specific pattern of congenital anomalies. " Somewhat more frequent than these trisomics, who are extremely rare, are patients who display various combinations of the anomalies of either syndrome, but have 46 chromosomes."9 Many of these cases are best interpreted as a result of partial trisomy,
The patient had an odd-shaped head, with wide occipitoparietal and narrow frontal diameters, and a peculiar facies characterised by bilateral ptosis with antimongoloid palpebral fissures, a broad flat nasal bridge, low-set large ears, a small receding mandible, and a small mouth with a cleft palate. There was polydactyly of the hands, and polydactyly with syndactyly of the feet. There was retroflexibility of the thumbs, and general spasticity. The external genitalia were those of a hypospadiac boy. A grade-n rough systolic murmur was audible to the left of the sternum with maximal intensity over the 2nd and 3rd intercostal spaces. Chest X-rays revealed a globular, generally hypertrophied heart with increased pulmonary vascularity. Measurements of the serum concentrations of CO2, chloride, sodium, potassium, calcium, phosphorus, and total protein did not yield any significant changes. The respiratory infection, which was complicated by enterocolitis and purulent otitis media, did not improve despite intensive antimicrobial treatment, and the child died suddenly after a short haematemesis after 5 weeks in hospital. At necropsy both lungs showed patchy areas of collapse. The ductus arteriosus was patent. Both ventricles of the heart, especially the left, were hypertrophied. The liver showed fatty degeneration, the left kidney was displaced downward, and the testicles were in the abdominal cavity. The brain was slightly underweight (300 g.). On histological examination, the heart showed endocardial fibroelastosis ; the brain appeared immature. There was persistence of the foetal granular layers in the cerebellum, and there were many patchy areas of undifferentiated glial tissue surrounding the ventricular system. Many neurons were necrotic or atrophic. There was striking proliferation of glial tissue, and the cells of the substantia nigra showed sclerotic changes. The chromosomes, which were counted in 15 cells from short-term leucocyte culture, all contained 46 chromosomes. 5 cells were analysed in detail-they showed apparently normal karyotypes. 3rd Pediatric Clinic, WANDA SZOTOWA Medical Academy, BARBARA KOWALEWSKA. Dzialdowska 1, Warsaw.
INTRINSIC-FACTOR ASSAY RESULTS SIR,-Dr. Ardeman and Dr. Chanarin (Aug. 14) state that the unit of intrinsic factor described by them in 19651 is the same as the one they described in 1963.2 Yet in 1963 they stated: It is suggested that one unit of intrinsic factor should be that amount that will promote the uptake of 1 (Jtmg. of 60CO- Vitamin B12 to normal serum ",2 and in 1965: This is expressed in units, one unit being the specific binding (i.e., to intrinsic factor) of one ung. of vitamin B12-"1 As we have written (Aug. 7), this change in their definition of a unit of intrinsic factor indicates that they have dropped their prior hypothesis1 on the mechanism of action of the charcoal assay, and have adopted the hypothesis we presented.3 Thus, their unit remains unchanged in that the number of jjtmg. of B12 is unchanged, but the definition of the unit is changed from intrinsic-factor-mediated uptake by serum to uptake by intrinsic "
"
although the structural alterations of the recipient chromosome are usually too small to be detected microscopically. We describe here a male infant with all the clinical characteristics of the trisomy-E-like syndrome, but with normal chromosome constitution. Unfortunately his chromosomes were examined from too few cells to test the possibility of mosaicism or
partial trisomy. The patient (see accompanying figure) was first seen by us at 5 weeks of age. His mother and father, aged 24 and 29 respectively, and his only sister, aged 3, were all healthy. The infant was delivered at term, the birth-weight being 2000 g., and the length 44 cm. He was admitted to our clinic because of respiratory infection with swallowing difficulties from birth. ,
Hecht, F., Loop, J. W., Graham, C. B. J. Pediat. (in the press). Ryder, C. T., Mellin, G. W., Caffey, J. Clin. Orthop. 1962, 22, 7. Caffey, J., Ross, S. Pediatrics, 1956, 17, 642. Caffey, J., Ross, S. J. Roentgenol. 1958, 80, 458. Hecht, F., Huehns, E. R., Lutzner, M. J. Pediat. 1964, 65, 1089. Huehns, E. R., Hecht, F., Keil, J. V., Motulsky, A. G. Proc. natn. Acad. Sci. U.S.A. 1964, 51, 89. 7. Weinstein, E. D., Rucknagel, D. L., Shaw, M. W. Am. J. hum. Genet. 1965, 17, 443. 8. Smith, D. W., Patau, K., Therman, E. Am. J. Dis. Child. 1961, 102, 1. 2. 3. 4. 5. 6.
587. 9.
Smith,
D.
W., Patau, K., Therman,
E.
Lancet, 1961, ii, 211.
factor. The other point made by Dr. Ardeman and Dr. Chanarin (Aug. 14) is that we fail to make allowance for a serum blank in the intrinsic-factor assay technique that we favour4 and that " this may on occasion introduce grave error, particularly in gastric-juice samples with low intrinsic-factor concentration ". This statement is not correct since our intrinsic-factor assay results are expressed thus: " The unsaturated B12 binding capacity of this gastric juice is x pg. of B12 per ml., of which y pg. are due to intrinsic factor."4 In order to arrive at y, obviously the relatively small unsaturated B12 binding capacity of the antibody must be added to the relatively large amount of reduction of B12 binding to gastric juice brought about by the Ardeman, S., Chanarin, I. Br. J. Hœmat. 1965, 11, 305. Ardeman, S., Chanarin, I. Lancet, 1963, ii, 1350. Herbert, V., Gottlieb, C., Lau, K.-S., Wasserman, L. R. ibid. 1964, ii, 1017. 4. Gottlieb, C., Lau, K.-S., Wasserman, L. R., Herbert, V. Blood, 1965, 25, 875. 1. 2. 3.