161
Case reports Magenis, R. E., Hecht, F., and Milham S. Jr. (1968). Trisomy 13 (D) syndrome: studies on parental age, sex ratio, and survival. journal of Pediatrics, 73, 222-228. Moorhead, P. S., Nowell, P. C., Mellman, W. J. Battips, D. M., and Hungerford, D. A. (1960). Chromosome preparations of leukocytes cultured from human peripheral blood. Experimental Research, 20, 613-616. Seabright, M. (1971). A rapid banding technique for human chromosomes. Lancet, 2, 971-972. Smith, D. W. (1970). Recognizable Patterns of Human Malformation, p. 368. W. B. Saunders, Philadelphia. Sumner, A. T., Evans, H. J., and Buckland, R. A. (1971). New technique for distinguishing between human chromosomes. Nature (London) New Biol., 232, 31-32.
r
:x
Familial ureteric bud anomalies Summary. A family is described in which various renal anomalies occurred. The condition is considered to represent an autosomal dominantly inherited 'instability' of the ureteric bud. There have been a number of reports on the occurrence of variable anomalies of ureteric bud development within a kindred (Atwell et al, 1974; Dietel, 1964; Nillson, 1960; Rossle, 1942). We report here the rare finding of double kidney, unilateral renal agenesis, and horseshoe kidney in two generations of one family.
Clinical findings
FIG. 1. II. 1. Intravenous pyelography showing failure of excretion of contrast medium by left kidney.
Discussion
Malformations arising from the ureteric bud are The proband, II.1, was the first daughter of unrelated and healthy Caucasian parents aged 29 and 45 years, common and, not infrequently, more than one respectively. Pregnancy and parturition were un- instance of a single anomaly is found in a kindred complicated and the birthweight was 2900 g. At (Atwell et al, 1974; Holmes, 1972; Lenz, 1964; routine neonatal physical examination (technique of Warkany, 1971). The occurrence of varying Museles et al, 1971) the left kidney was not palpable; no anomalies within a kindred is rare, and we have other defects were detected. Intravenous pyelography found only four reported instances in which two or (Fig. 1) failed to detect functioning renal tissue on the same side. The presumptive diagnosis was left renal more of the three above anomalies were found agenesis. At follow-up no additional anomalies were together. One of these examples was associated detected. The karyotype was that of a normal female. with Fanconi's anaemia (Nillson, 1960). The present family is of interest from the aspects The second pregnancy resulted in the birth of an apparently healthy boy, II.2, following a normal preg- of both aetiology and pathogenesis. Discussion of nancy and parturition. Birthweight was 3410 g. the latter requires consideration of the embryology Physical examination revealed a horseshoe kidney as the of the kidney and collecting system. only abnormal finding, and both renal scan (Fig. 2) and The human definitive kidney (metanephros) intravenous pyelography confirmed the diagnosis. arises from two embryonic sources. The interAs a result of the above findings the parents underwent radiological studies of the kidneys. The father mediate (metanephric) mesoderm which differenwas normal but in the mother, I. 1, a right double kidney tiates into the nephron and connective tissue of the kidney; and the ureteric (metanephric) bud which and collecting system were disclosed (Fig. 3). There was no family history of renal disease or of arises from the mesonephric (Wolffian) duct, and hypertension. The mother's parents and only sib gives rise to the collecting system of the kidney refused to undergo pyelography. (Potter, 1972; Warkany 1971).
Case reports
162
IJ
FIG. 2. 11.2. Renal scan (A.P.): horseshoe kidney.
7
2
Most of the congenital anomalies involving the kidney arise from a primary defect of the ureteric bud, either during its formation and growth (as in agenesis of the kidney), or as a result of disturbances of its inductive function in nephron formation (as in some types of polycystic kidney). Relatively few anomalies are attributed to a primary defect of mesoderm (for example, solitary the i lll E metanephric cysts of the renal parenchyma). Unilateral agenesis can be explained by a unilateral failure of the normal growth of the ureteral bud. As a consequence the intermediate mesoderm on the same side fails to differentiate into kidney parenchyma. Boyden showed, as early as 1927, that interference with growth of the mesonephric duct can cause renal agenesis (Boyden, 1927). Horseshoe kidneys are formed when the ureteric
buds grow upwards nearer to the midline than normally (Warkany, 1971). In the early stages of renal development the lower poles are more closely approximated than the upper (Potter, 1972). This may explain why horseshoe kidneys are usually fused at their lower poles. 'When a mesonephric duct gives rise to two j buds on one or both sides, the result is Iklureteral FIG. 3. 1.1. Intravenous pyelography: right double kidney and
collecting system.
Case reports
duplication of the ureters, and, frequently, separate renal pelves and kidney are formed in the metanephric blastema as well. A number of teratogenic agents, such as chlorambucil, methyl salicylate, vitamin A deficiency, and irradiation (reviewed by Warkany, 1971), have been shown to give rise to ureteric bud anomalies. In addition, the incidence of the above anomalies is increased in some chromosomal aberrations. In trisomy 18 there is a high incidence of double kidney, unilateral renal agenesis, and horseshoe kidney (Warkany, 1971). Ureteric bud anomalies also occur in association with Fanconi's anaemia together with other malformations; the condition is inherited by an autosomal recessive gene (Nillson, 1960). The frequency of the described anomalies in the general population is approximately as follows: unilateral agenesis, 1 in 600; horseshoe kidney, 1 in 400; ureteral duplication including double kidney, 1 in 150 (Warkany, 1971). There is increasing evidence that some instances of the renal anomalies encountered in this kindred are of genetic origin (Atwell et al, 1974; Holmes, 1972). It is highly probable that the concentration of renal anomalies in the presently,described family is a result of inheritance. Though data are available for only four individuals in this family, the renal anomaly predisposition appears to be inherited by an autosomal dominant gene. The gene appears to cause 'instability' of the ureteric bud, resulting in
163
the production of variable anomalies of the kidneys and collecting system.
M. PERLMAN,* J. WILLIAMS, A. ORNOY The Soroka Medical Center, Beer Sheva; and the Department of Anatomy and Embryology, HebrewUniversity Hadassah Medical School, Jerusalem, Israel REFERENCES Atwell, J. D., Cook, P. L., Howell, C. J., Hyde, I., and Parker, B. C. (1974). Familial incidence of bifid and double ureters. Archives of Diseases in Childhood, 49, 390-393. Boyden, E. A. (1927). Experimental obstruction of the metanephric duct. Proceedings of the Society for Experimental Biology and Medicine, 24, 572-576. Dietel, H. (1964). Cited in Lenz (1964), p. 256. Holmes, L. B. (1972). Unilateral renal agenesis: Common, Serious, ? hereditary. Pediatric Research, 6, 419. Lenz, W. (1964). Humangenetik, Vol. 3, part 1, ed. by B. E. Becker. Georg Thieme, Stuttgart. Museles, M., Gaudry, C. L., Jr., and Bason, W. M. (1971). Renal anomalies in the newborn found by deep palpation. Pediatrics, 47, 97-100. Nillson, L. R. (1960). Chronic pancytopenia with multiple congenital anomalies. (Fanconi's anemia.) Acta Paediatrica Scandinavica, 49, 518-529. Potter, E. L. (1972). Normal and Abnormal Development of the Kidney. Year Book Medical Publishers, Chicago. Rossle, R. (1942). Weitere Beobachtungen uber Sektionsbefunde bei Blutsverwandten. Archiv fur Pathologische Anatomie, 308, 495-507. Warkany, J. (1971). Congenital Malformations. Notes and Comments, pp. 1037-1073. Year Book Medical Publishers, Chicago.
* Present address: Neonatal Unit, Pediatric Department, Hadassah University Hospital, Jerusalem, Israel.
Case reports Magenis, R. E., Hecht, F., and Milham S. Jr. (1968). Trisomy 13 (D) syndrome: studies on parental age, sex ratio, and survival. journal of Pediatrics, 73, 222-228. Moorhead, P. S., Nowell, P. C., Mellman, W. J. Battips, D. M., and Hungerford, D. A. (1960). Chromosome preparations of leukocytes cultured from human peripheral blood. Experimental Research, 20, 613-616. Seabright, M. (1971). A rapid banding technique for human chromosomes. Lancet, 2, 971-972. Smith, D. W. (1970). Recognizable Patterns of Human Malformation, p. 368. W. B. Saunders, Philadelphia. Sumner, A. T., Evans, H. J., and Buckland, R. A. (1971). New technique for distinguishing between human chromosomes. Nature (London) New Biol., 232, 31-32.
r
:x
Familial ureteric bud anomalies Summary. A family is described in which various renal anomalies occurred. The condition is considered to represent an autosomal dominantly inherited 'instability' of the ureteric bud. There have been a number of reports on the occurrence of variable anomalies of ureteric bud development within a kindred (Atwell et al, 1974; Dietel, 1964; Nillson, 1960; Rossle, 1942). We report here the rare finding of double kidney, unilateral renal agenesis, and horseshoe kidney in two generations of one family.
Clinical findings
FIG. 1. II. 1. Intravenous pyelography showing failure of excretion of contrast medium by left kidney.
Discussion
Malformations arising from the ureteric bud are The proband, II.1, was the first daughter of unrelated and healthy Caucasian parents aged 29 and 45 years, common and, not infrequently, more than one respectively. Pregnancy and parturition were un- instance of a single anomaly is found in a kindred complicated and the birthweight was 2900 g. At (Atwell et al, 1974; Holmes, 1972; Lenz, 1964; routine neonatal physical examination (technique of Warkany, 1971). The occurrence of varying Museles et al, 1971) the left kidney was not palpable; no anomalies within a kindred is rare, and we have other defects were detected. Intravenous pyelography found only four reported instances in which two or (Fig. 1) failed to detect functioning renal tissue on the same side. The presumptive diagnosis was left renal more of the three above anomalies were found agenesis. At follow-up no additional anomalies were together. One of these examples was associated detected. The karyotype was that of a normal female. with Fanconi's anaemia (Nillson, 1960). The present family is of interest from the aspects The second pregnancy resulted in the birth of an apparently healthy boy, II.2, following a normal preg- of both aetiology and pathogenesis. Discussion of nancy and parturition. Birthweight was 3410 g. the latter requires consideration of the embryology Physical examination revealed a horseshoe kidney as the of the kidney and collecting system. only abnormal finding, and both renal scan (Fig. 2) and The human definitive kidney (metanephros) intravenous pyelography confirmed the diagnosis. arises from two embryonic sources. The interAs a result of the above findings the parents underwent radiological studies of the kidneys. The father mediate (metanephric) mesoderm which differenwas normal but in the mother, I. 1, a right double kidney tiates into the nephron and connective tissue of the kidney; and the ureteric (metanephric) bud which and collecting system were disclosed (Fig. 3). There was no family history of renal disease or of arises from the mesonephric (Wolffian) duct, and hypertension. The mother's parents and only sib gives rise to the collecting system of the kidney refused to undergo pyelography. (Potter, 1972; Warkany 1971).
Case reports
162
IJ
FIG. 2. 11.2. Renal scan (A.P.): horseshoe kidney.
7
2
Most of the congenital anomalies involving the kidney arise from a primary defect of the ureteric bud, either during its formation and growth (as in agenesis of the kidney), or as a result of disturbances of its inductive function in nephron formation (as in some types of polycystic kidney). Relatively few anomalies are attributed to a primary defect of mesoderm (for example, solitary the i lll E metanephric cysts of the renal parenchyma). Unilateral agenesis can be explained by a unilateral failure of the normal growth of the ureteral bud. As a consequence the intermediate mesoderm on the same side fails to differentiate into kidney parenchyma. Boyden showed, as early as 1927, that interference with growth of the mesonephric duct can cause renal agenesis (Boyden, 1927). Horseshoe kidneys are formed when the ureteric
buds grow upwards nearer to the midline than normally (Warkany, 1971). In the early stages of renal development the lower poles are more closely approximated than the upper (Potter, 1972). This may explain why horseshoe kidneys are usually fused at their lower poles. 'When a mesonephric duct gives rise to two j buds on one or both sides, the result is Iklureteral FIG. 3. 1.1. Intravenous pyelography: right double kidney and
collecting system.
Case reports
duplication of the ureters, and, frequently, separate renal pelves and kidney are formed in the metanephric blastema as well. A number of teratogenic agents, such as chlorambucil, methyl salicylate, vitamin A deficiency, and irradiation (reviewed by Warkany, 1971), have been shown to give rise to ureteric bud anomalies. In addition, the incidence of the above anomalies is increased in some chromosomal aberrations. In trisomy 18 there is a high incidence of double kidney, unilateral renal agenesis, and horseshoe kidney (Warkany, 1971). Ureteric bud anomalies also occur in association with Fanconi's anaemia together with other malformations; the condition is inherited by an autosomal recessive gene (Nillson, 1960). The frequency of the described anomalies in the general population is approximately as follows: unilateral agenesis, 1 in 600; horseshoe kidney, 1 in 400; ureteral duplication including double kidney, 1 in 150 (Warkany, 1971). There is increasing evidence that some instances of the renal anomalies encountered in this kindred are of genetic origin (Atwell et al, 1974; Holmes, 1972). It is highly probable that the concentration of renal anomalies in the presently,described family is a result of inheritance. Though data are available for only four individuals in this family, the renal anomaly predisposition appears to be inherited by an autosomal dominant gene. The gene appears to cause 'instability' of the ureteric bud, resulting in
163
the production of variable anomalies of the kidneys and collecting system.
M. PERLMAN,* J. WILLIAMS, A. ORNOY The Soroka Medical Center, Beer Sheva; and the Department of Anatomy and Embryology, HebrewUniversity Hadassah Medical School, Jerusalem, Israel REFERENCES Atwell, J. D., Cook, P. L., Howell, C. J., Hyde, I., and Parker, B. C. (1974). Familial incidence of bifid and double ureters. Archives of Diseases in Childhood, 49, 390-393. Boyden, E. A. (1927). Experimental obstruction of the metanephric duct. Proceedings of the Society for Experimental Biology and Medicine, 24, 572-576. Dietel, H. (1964). Cited in Lenz (1964), p. 256. Holmes, L. B. (1972). Unilateral renal agenesis: Common, Serious, ? hereditary. Pediatric Research, 6, 419. Lenz, W. (1964). Humangenetik, Vol. 3, part 1, ed. by B. E. Becker. Georg Thieme, Stuttgart. Museles, M., Gaudry, C. L., Jr., and Bason, W. M. (1971). Renal anomalies in the newborn found by deep palpation. Pediatrics, 47, 97-100. Nillson, L. R. (1960). Chronic pancytopenia with multiple congenital anomalies. (Fanconi's anemia.) Acta Paediatrica Scandinavica, 49, 518-529. Potter, E. L. (1972). Normal and Abnormal Development of the Kidney. Year Book Medical Publishers, Chicago. Rossle, R. (1942). Weitere Beobachtungen uber Sektionsbefunde bei Blutsverwandten. Archiv fur Pathologische Anatomie, 308, 495-507. Warkany, J. (1971). Congenital Malformations. Notes and Comments, pp. 1037-1073. Year Book Medical Publishers, Chicago.
* Present address: Neonatal Unit, Pediatric Department, Hadassah University Hospital, Jerusalem, Israel.
