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Urological Manifestations of the Melnick-Needles Syndrome: A Case Report and Review of the Literature
0022-534 7/91/1455-1020$03.00/0 Vol. 145, 1020-1021, May 1991 Printed in U.S.A.
THE JOURNAL OF UROLOGY Copyright© 1991 by AMERICAN UROLOGICAL ASSOCIATION, INC.
UROLOGICAL MANIFESTATIONS OF THE MELNICK-NEEDLES SYNDROME: A CASE REPORT AND REVIEW OF THE LITERATURE ARTHUR E. LAMONTAGNE From the Department of Urology, Rockville General Hospital, Rockville, Connecticut
ABSTRACT
In 1966 Melnick and Needles described a syndrome of multiple skeletal anomalies in a 3-year-old girl. A dilated ureter was noted but not associated with the disorder. Subsequent to this report there have been 8 additional cases published of patients with the Melnick-Needles syndrome in association with a variety of urogenital and abdominal wall abnormalities. A 10-year-old girl with this syndrome and bilateral ureteral ectasia is described and the literature on this association is reviewed. KEY
W OROS: osteochondrodysplasias, ureteral diseases
In 1966 Melnick and Needles reported on a 3-year-old white girl with severe craniofacial deformity and multiple bony abnormalities of the chest, abdomen and long bones, for which they coined the syndrome of osteodysplasia that bears their names. 1 Of 14 family members in 4 generations 9 exhibited some degree of involvement. Features of this syndrome include micrognathia, exophthalmos, full cheeks, dental malocclusion and large ears. The long bones show cortical irregularities, with flaring of the metaphyses, bowing of the radius and tibia, and ribbon-like deformities of the ribs. Additional features include coxa valga, short stature, an increase in height with anterior concavity of the vertebral bodies, a delay in closure of the anterior fontanelle and sclerosis at the base of the skull. Pelvic abnormalities include flattening and flaring of the iliac bones, tapering of the ischia and hypoplasia of the pubic rami with flattening of the acetabulum. An incidental finding of left hydronephrosis and hydroureter was described in the proband of the family studied by Melnick and Needles. Since their report there have been scattered isolated reports of urological abnormalities in individuals afflicted with the syndrome.
thereby, not recognized as the Melnick-Needles syndrome, which accounts for the fact that the apparent sex ratio is different from what would be predicted by the laws of Mendelian genetics. In 1977 Klint et al described a 3½-year-old girl with the Melnick-Needles syndrome, and right hydronephrosis and hydroureter down to the level of the ureterovesical junction. 2 Reflux was not observed on a voiding cystourethrogram. The authors noted that the first patient reported on by Melnick and Needles also had a stricture of the ureterovesical junction and hydronephrosis but they did not expand upon the relationship. In 1981 Theander and Ekberg reported on a male newborn of an afflicted mother. 3 The neonate had a large omphalocele and died several minutes post partum. In 1982 von Oeyen et al described an additional case of the Melnick-Needles syndrome in a 24-year-old woman who gave birth to a severely affected male infant who died after 1 hour. 4 The neonate was noted to have a large omphalocele, bilateral cryptorchid testes and bilateral polycystic kidneys (Potter type IIB) as well as left ureteral hypoplasia.
CASE REPORT
J. D., a 10-year-old white girl, presented with fever a,nd left abdominal pain of short duration. She was treated for a urinary infection by the pediatrician. Renal ultrasound showed left hydronephrosis and the patient was referred for urological evaluation. The child and her mother were previously diagnosed as having the Melnick-Needles syndrome. Physical examination of the child revealed the typical facial features of the disorder. She had no abdominal masses but exhibited marked left flank tenderness. Antibiotics were continued and an excretory urogram (IVP) revealed bilateral ureteral dilatation, greater on the left than on the right side (see figure). The renal collecting systems appeared normal. A subsequent voiding cystourethrogram failed to reveal reflux. The child improved on antibiotics and will be followed with periodic ultrasound studies of the urinary tract to monitor renal growth and anatomy. DISCUSSION
Since the initial case report in 1966, a number of investigators have described additional patients with the Melnick-Needles syndrome and its variants, leading to a better understanding of its genetic expression and transmission. This disorder was originally thought to be transmitted as an autosomal dominant trait with a female-to-male ratio of 1:1. However, recent evidence now indicates a sex-linked dominant mode. Male subjects are more severely afflicted than female subjects. Also, the disorder is frequently fatal prenatally in male subjects and, Accepted for publication September 19, 1990.
IVP shows bilateral ureterectasia, ribbon-like rib deformities as well as pelvic and spinal deformities typical of Melnick-Needles syndrome.
1020
UROLOGICAL MANIFESTATIONS OF iv1ELNICK-NEEDLES SYNDROME
In 1983 Bartolozzi et al reported on a 12-year-old girl with the Melnick-Needles syndrome and dilatation of the ureter, pelvis and calices of the right kidney. 5 Deleporte et al noted dysplastic kidneys, a dilated right ureter, duplication of the left ureter and megacystis in a male stillborn of a mother afflicted with the Melnick-Needles syndrome. 6 An interesting case of prenatally determined Melnick-Needles syndrome was described in 1987 by Donnenfeld et al. 7 A prenatal fetal ultrasound on a 29-year-old woman with the disorder revealed a suspected omphalocele along with oligohydramnios. Fetal death was confirmed at 17 weeks and uterine emptying was induced. The male fetus had a lax, protuberant abdominal wall characteristic of the prune belly syndrome. In addition, there was distal urethral atresia, dilatation of the prostatic urethra and megacystis, and bilateral intra-abdominal testes. The kidneys were normal in this case. Donnenfeld et al concluded that the male expression of the Melnick-Needles syndrome was inconsistent with life, and that since no male subjects reproduced, X-linked dominant inheritance could not be distinguished from autosomal dominant, sex-limited inheritance on the basis of the offspring of afflicted women. However, in 1987 Krajewska-Walasek et al reported a case of the Melnick-Needles syndrome in a boy who lived to age 3 years. 8 They explained their case as well as 2 other cases of living male subjects9 • 10 on the basis of new genetic mutations. They also described an additional unpublished case of an afflicted Melnick-Needles syndrome mother whose male stillborn had ambiguous genitalia (hooded prepuce, urethral atresia, partially fused labioscrotal folds), omphalocele, male and female internal organs, and intra-abdominal testes. Exner described a variant of the Melnick-Needles syndrome in a 5-yearold girl with polycystic kidneys 11 and related this case to one previously reported by Dereymaeker et al without any reported genitourinary anomalies. 12 Finally, an additional male infant with the typical Melnick-Needles syndrome phenotype, born to apparently healthy, unaffected parents, was described in 1988 by Fryns et al. 13 This child had a large umbilical hernia and bilateral inguinal hernias, diastasis recti with poor development of the abdominal musculature and generalized laxity of the skin. They noted similar features in other male subjects reported as having the Melnick-Needles syndrome and postulated the relationship between this syndrome and the prune belly sequence. Fryns et al also suggested that the MelnickNeedles syndrome be classified as another entity among the group of connective tissue disorders. CONCLUSION
The Melnick-Needles syndrome is an X-linked dominant genetically transmitted connective tissue disorder characterized by multiple bony and soft tissue anomalies. It was reported initially in the radiological literature and subsequent reports have appeared in orthopedic and genetics publications. This
1021
review of the urological manifestations of the Melnick-Needles syndrome was prompted by a case associated with hydronephrosis. It appears that the Melnick-Needles syndrome is one of a number of connective tissue disorders, which include the prune belly syndrome so well known to urologists. There is a wide spectrum of genitourinary tract involvement in this disorder but this association should prompt the thoughtful urologist to be aware of genitourinary anomalies in patients with the typical phenotype of the Melnick-Needles syndrome. REFERENCES 1. Melnick, J.C. and Needles, C. F.: An undiagnosed bone dysplasia.
A 2 family study of 4 generations and 3 generations. AJR, 97: 39, 1966.
2. Klint, R. B., Agustsson, M. H. and McAlister, W. H.: MelnickNeedles osteodysplasia associated with pulmonary hypertension, obstructive uropathy and marrow hypoplasia. Ped. Rad., 6: 49, 1977.
3. Theander, G. and Ekberg, 0.: Congenital malformations associated with maternal osteodysplasty. A new malformation complex. Acta Rad., 22: 369, 1981. 4. von Oeyen, P., Holmes, L.B., Trelstad, R. L. and Griscom, N. T.: Omphalocele and multiple severe congenital anomalies associated with osteodysplasty (Melnick-Needles syndrome). Amer. J. Med. Genet., 13: 453, 1982. 5. Bartolozzi, P., Calabrese, C., Falcini, F., Giovannucci Uzzielli, M. L. and Maggini, M.: Melnick-Needles syndrome: osteodysplasty with kyphoscoliosis. J. Ped. Orthoped., 3: 387, 1983. 6. Deleporte, B., Buissart, J.P., Vankemmel, P ., Remy, J., Maroteaux, P., Galley, F., Savary, J., Fournier, J. L. and Fontaine, G.: L'osteodysplastie ou syndrome de Melnick et Needles; (apropos d'une nouvelle observation). J. Genet. Hum., 33: 13, 1985. 7. Donnenfeld, A. E., Conard, K. A., Roberts, N. S., Borns, P. F. and Zackai, E. H.: Melnick-Needles syndrome in males: a lethal multiple congenital anomalies syndrome. Amer. J. Med. Genet., 27: 159, 1987. 8. Krajewska-Walasek, M., Winkielman, J. and Gorlin, R. J.: Melnick-Needles syndrome in males. Amer. J. Med. Genet., 27: 153, 1987. 9. Grosse, K.-P. and Bowing, B.: Osteodysplastie. In: Klinische Ge-
netik in der Padiatrie. Edited by J. Spranger and M. Tolkodorf. Stuttgart: Thieme Verlag, vol. 1, pp. 80-86, 1980. 10. Theodorou, S. D., Ierodiaconou, M. N., Gerostathopoulos, N. and Grivas, T.: Osteodysplasty (Melnick-Needles syndrome) in a male. In: Skeletal Dysplasias. Edited by C. J. Papadatos and C. S. Bartsocas. New York: Alan R. Liss, Inc., pp. 139-142, 1982. 11. Exner, G. U.: Serpentine fibula-polycystic kidney syndrome. A variant of the Melnick-Needles syndrome or a distinct entity? Eur. J. Ped., 147: 544, 1988. 12. Dereymaeker, A. M., Christens, J., Eeckels, R., Heremans, G. and Fryns, J. P.: Melnick-Needles syndrome (osteodysplasty). Clinical and radiological heterogeneity. Helv. Paed. Acta, 41: 339, 1986. 13. Fryns, J.P., Schinzel, A. and Van den Berghe, H.: Hyperlaxity in
males with Melnick-Needles syndrome. Amer. J. Med. Genet., 29: 607, 1988.
THE JOURNAL OF UROLOGY Copyright© 1991 by AMERICAN UROLOGICAL ASSOCIATION, INC.
UROLOGICAL MANIFESTATIONS OF THE MELNICK-NEEDLES SYNDROME: A CASE REPORT AND REVIEW OF THE LITERATURE ARTHUR E. LAMONTAGNE From the Department of Urology, Rockville General Hospital, Rockville, Connecticut
ABSTRACT
In 1966 Melnick and Needles described a syndrome of multiple skeletal anomalies in a 3-year-old girl. A dilated ureter was noted but not associated with the disorder. Subsequent to this report there have been 8 additional cases published of patients with the Melnick-Needles syndrome in association with a variety of urogenital and abdominal wall abnormalities. A 10-year-old girl with this syndrome and bilateral ureteral ectasia is described and the literature on this association is reviewed. KEY
W OROS: osteochondrodysplasias, ureteral diseases
In 1966 Melnick and Needles reported on a 3-year-old white girl with severe craniofacial deformity and multiple bony abnormalities of the chest, abdomen and long bones, for which they coined the syndrome of osteodysplasia that bears their names. 1 Of 14 family members in 4 generations 9 exhibited some degree of involvement. Features of this syndrome include micrognathia, exophthalmos, full cheeks, dental malocclusion and large ears. The long bones show cortical irregularities, with flaring of the metaphyses, bowing of the radius and tibia, and ribbon-like deformities of the ribs. Additional features include coxa valga, short stature, an increase in height with anterior concavity of the vertebral bodies, a delay in closure of the anterior fontanelle and sclerosis at the base of the skull. Pelvic abnormalities include flattening and flaring of the iliac bones, tapering of the ischia and hypoplasia of the pubic rami with flattening of the acetabulum. An incidental finding of left hydronephrosis and hydroureter was described in the proband of the family studied by Melnick and Needles. Since their report there have been scattered isolated reports of urological abnormalities in individuals afflicted with the syndrome.
thereby, not recognized as the Melnick-Needles syndrome, which accounts for the fact that the apparent sex ratio is different from what would be predicted by the laws of Mendelian genetics. In 1977 Klint et al described a 3½-year-old girl with the Melnick-Needles syndrome, and right hydronephrosis and hydroureter down to the level of the ureterovesical junction. 2 Reflux was not observed on a voiding cystourethrogram. The authors noted that the first patient reported on by Melnick and Needles also had a stricture of the ureterovesical junction and hydronephrosis but they did not expand upon the relationship. In 1981 Theander and Ekberg reported on a male newborn of an afflicted mother. 3 The neonate had a large omphalocele and died several minutes post partum. In 1982 von Oeyen et al described an additional case of the Melnick-Needles syndrome in a 24-year-old woman who gave birth to a severely affected male infant who died after 1 hour. 4 The neonate was noted to have a large omphalocele, bilateral cryptorchid testes and bilateral polycystic kidneys (Potter type IIB) as well as left ureteral hypoplasia.
CASE REPORT
J. D., a 10-year-old white girl, presented with fever a,nd left abdominal pain of short duration. She was treated for a urinary infection by the pediatrician. Renal ultrasound showed left hydronephrosis and the patient was referred for urological evaluation. The child and her mother were previously diagnosed as having the Melnick-Needles syndrome. Physical examination of the child revealed the typical facial features of the disorder. She had no abdominal masses but exhibited marked left flank tenderness. Antibiotics were continued and an excretory urogram (IVP) revealed bilateral ureteral dilatation, greater on the left than on the right side (see figure). The renal collecting systems appeared normal. A subsequent voiding cystourethrogram failed to reveal reflux. The child improved on antibiotics and will be followed with periodic ultrasound studies of the urinary tract to monitor renal growth and anatomy. DISCUSSION
Since the initial case report in 1966, a number of investigators have described additional patients with the Melnick-Needles syndrome and its variants, leading to a better understanding of its genetic expression and transmission. This disorder was originally thought to be transmitted as an autosomal dominant trait with a female-to-male ratio of 1:1. However, recent evidence now indicates a sex-linked dominant mode. Male subjects are more severely afflicted than female subjects. Also, the disorder is frequently fatal prenatally in male subjects and, Accepted for publication September 19, 1990.
IVP shows bilateral ureterectasia, ribbon-like rib deformities as well as pelvic and spinal deformities typical of Melnick-Needles syndrome.
1020
UROLOGICAL MANIFESTATIONS OF iv1ELNICK-NEEDLES SYNDROME
In 1983 Bartolozzi et al reported on a 12-year-old girl with the Melnick-Needles syndrome and dilatation of the ureter, pelvis and calices of the right kidney. 5 Deleporte et al noted dysplastic kidneys, a dilated right ureter, duplication of the left ureter and megacystis in a male stillborn of a mother afflicted with the Melnick-Needles syndrome. 6 An interesting case of prenatally determined Melnick-Needles syndrome was described in 1987 by Donnenfeld et al. 7 A prenatal fetal ultrasound on a 29-year-old woman with the disorder revealed a suspected omphalocele along with oligohydramnios. Fetal death was confirmed at 17 weeks and uterine emptying was induced. The male fetus had a lax, protuberant abdominal wall characteristic of the prune belly syndrome. In addition, there was distal urethral atresia, dilatation of the prostatic urethra and megacystis, and bilateral intra-abdominal testes. The kidneys were normal in this case. Donnenfeld et al concluded that the male expression of the Melnick-Needles syndrome was inconsistent with life, and that since no male subjects reproduced, X-linked dominant inheritance could not be distinguished from autosomal dominant, sex-limited inheritance on the basis of the offspring of afflicted women. However, in 1987 Krajewska-Walasek et al reported a case of the Melnick-Needles syndrome in a boy who lived to age 3 years. 8 They explained their case as well as 2 other cases of living male subjects9 • 10 on the basis of new genetic mutations. They also described an additional unpublished case of an afflicted Melnick-Needles syndrome mother whose male stillborn had ambiguous genitalia (hooded prepuce, urethral atresia, partially fused labioscrotal folds), omphalocele, male and female internal organs, and intra-abdominal testes. Exner described a variant of the Melnick-Needles syndrome in a 5-yearold girl with polycystic kidneys 11 and related this case to one previously reported by Dereymaeker et al without any reported genitourinary anomalies. 12 Finally, an additional male infant with the typical Melnick-Needles syndrome phenotype, born to apparently healthy, unaffected parents, was described in 1988 by Fryns et al. 13 This child had a large umbilical hernia and bilateral inguinal hernias, diastasis recti with poor development of the abdominal musculature and generalized laxity of the skin. They noted similar features in other male subjects reported as having the Melnick-Needles syndrome and postulated the relationship between this syndrome and the prune belly sequence. Fryns et al also suggested that the MelnickNeedles syndrome be classified as another entity among the group of connective tissue disorders. CONCLUSION
The Melnick-Needles syndrome is an X-linked dominant genetically transmitted connective tissue disorder characterized by multiple bony and soft tissue anomalies. It was reported initially in the radiological literature and subsequent reports have appeared in orthopedic and genetics publications. This
1021
review of the urological manifestations of the Melnick-Needles syndrome was prompted by a case associated with hydronephrosis. It appears that the Melnick-Needles syndrome is one of a number of connective tissue disorders, which include the prune belly syndrome so well known to urologists. There is a wide spectrum of genitourinary tract involvement in this disorder but this association should prompt the thoughtful urologist to be aware of genitourinary anomalies in patients with the typical phenotype of the Melnick-Needles syndrome. REFERENCES 1. Melnick, J.C. and Needles, C. F.: An undiagnosed bone dysplasia.
A 2 family study of 4 generations and 3 generations. AJR, 97: 39, 1966.
2. Klint, R. B., Agustsson, M. H. and McAlister, W. H.: MelnickNeedles osteodysplasia associated with pulmonary hypertension, obstructive uropathy and marrow hypoplasia. Ped. Rad., 6: 49, 1977.
3. Theander, G. and Ekberg, 0.: Congenital malformations associated with maternal osteodysplasty. A new malformation complex. Acta Rad., 22: 369, 1981. 4. von Oeyen, P., Holmes, L.B., Trelstad, R. L. and Griscom, N. T.: Omphalocele and multiple severe congenital anomalies associated with osteodysplasty (Melnick-Needles syndrome). Amer. J. Med. Genet., 13: 453, 1982. 5. Bartolozzi, P., Calabrese, C., Falcini, F., Giovannucci Uzzielli, M. L. and Maggini, M.: Melnick-Needles syndrome: osteodysplasty with kyphoscoliosis. J. Ped. Orthoped., 3: 387, 1983. 6. Deleporte, B., Buissart, J.P., Vankemmel, P ., Remy, J., Maroteaux, P., Galley, F., Savary, J., Fournier, J. L. and Fontaine, G.: L'osteodysplastie ou syndrome de Melnick et Needles; (apropos d'une nouvelle observation). J. Genet. Hum., 33: 13, 1985. 7. Donnenfeld, A. E., Conard, K. A., Roberts, N. S., Borns, P. F. and Zackai, E. H.: Melnick-Needles syndrome in males: a lethal multiple congenital anomalies syndrome. Amer. J. Med. Genet., 27: 159, 1987. 8. Krajewska-Walasek, M., Winkielman, J. and Gorlin, R. J.: Melnick-Needles syndrome in males. Amer. J. Med. Genet., 27: 153, 1987. 9. Grosse, K.-P. and Bowing, B.: Osteodysplastie. In: Klinische Ge-
netik in der Padiatrie. Edited by J. Spranger and M. Tolkodorf. Stuttgart: Thieme Verlag, vol. 1, pp. 80-86, 1980. 10. Theodorou, S. D., Ierodiaconou, M. N., Gerostathopoulos, N. and Grivas, T.: Osteodysplasty (Melnick-Needles syndrome) in a male. In: Skeletal Dysplasias. Edited by C. J. Papadatos and C. S. Bartsocas. New York: Alan R. Liss, Inc., pp. 139-142, 1982. 11. Exner, G. U.: Serpentine fibula-polycystic kidney syndrome. A variant of the Melnick-Needles syndrome or a distinct entity? Eur. J. Ped., 147: 544, 1988. 12. Dereymaeker, A. M., Christens, J., Eeckels, R., Heremans, G. and Fryns, J. P.: Melnick-Needles syndrome (osteodysplasty). Clinical and radiological heterogeneity. Helv. Paed. Acta, 41: 339, 1986. 13. Fryns, J.P., Schinzel, A. and Van den Berghe, H.: Hyperlaxity in
males with Melnick-Needles syndrome. Amer. J. Med. Genet., 29: 607, 1988.