- Email: [email protected]
Urological Implications of the Beckwith-Wiedemann Syndrome
G022"5347 /8l/l253-:J439$02.0D/0 1/
THE JO-U-3.NAL OF UROI,OG-Y
CopyT:ight © 1981 by The V,filifa.rn..s & Vi/ilk.ins Co.
uL 125 1 lviarch
Printed in U.S.A.
UROLOGICAL IIVl:PLICATIONS THE BECKVVITH-\IVIEDEivIANN SYNDROME WILLIAM N. TAYLOR From the Department of Surgery, Section of Urology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina
ABSTRACT
A significant number of children with the Beckwith-Wiedemann syndrome are prone to the development of nephroblastomas and adrenal carcinomas. Renomegaly, a prolonged tubular blush on excretory urography similar to that of medullary sponge kidney, and previously undescribed caliceal diverticula may be observed. Diligent follovvup is mandatory to detect early neoplasia. Suggestions are detailed based on reported case management. The Beckwith-Wiedemann or E.M.G. (exomphalos, macroglossia and gigantism) syndrome is a rare syndrome reported independently by Beckwith and Wiedemann in 1964 and >200 cases subsequently have been reported mainly in the pediatric and pathology literature. 1• 2 In essence, the striking criteria of this syndrome are macroglossia, macrostomia and exomphalos at birth, and hemihypertrophy or gigantism that may develop later. Familial cases believed to be inherited as an autosomal dominant are frequent but many cases are sporadic. No consistent chromosomal defect has been detected and the disease pr-esents in partial forms with some of the stigmas only. Birth
areas of renal blastema formation at the corticomedullary junction that are believed to be potentially oncogenic. 4 The medullary architecture is disorganized, lacks linearity and has increased stroma with fewer collecting ducts, which are dilated.3· 4 Of the patients >10 per cent will suffer neoplasms in early childhood, with Wilms tumor and adrenal carcinoma being predominant.' Other malignant tumors are hepatoblastomas, sarcomas, gonadoblastomas and neural tumors. Radiological features with contrast medium show a prolonged tubular opacification similar to medullary sponge kidney, and not described previously are cystic areas in the forniceal region
Fm. 1. A, typical slit-like earlobe fissure. B, macroglossia and macrostomia
weight usually is greater than the 90th percentile and other features are a flame nevus in the metopic region that fades with time, deep earlobe fissures, diastasis of the recti, undescended testes, cardiac anomalies, malrotation of the bowel and eventration of the diaphragm. Perinatal hypoglycemia makes recognition of this syndrome at birth imperative since it frequently is fatal if untreated. Pathological examination of the kidneys shows excessive lobulation and each kidney weighs 3 to 4 times more than normal. 3 Microscopically, there is increased glomeruloneogenesis, particularly at the inner cortex, and there are discrete Accepted for publication May 9, 1980. 439
suggestive of caliceal diverticula. Similar diverticuJa are evident but not described in the literature. s-s These diverticula are filled easily on retrograde pyelography, are non-obstructive and do not increase in size proportional to renal growth. Neither defect appears to have a deleterious effect on renal function. CASE REPORT
The patient was the third sibling of normal parents, the first 2 dying shortly after birth, presumably of hypoglycemia. Birth weight was 10 pounds 4 ounces. Macroglossia, macrostomia, a
flame nevus in the metopic region, fissures in the earlobes and an undescended testis were present (fig. 1). Hypoglycemia (25
440
TAYLOR
0
RIGHT
QG
(_o (
(\\.\
LEFT Fm. 2. A, right kidney with multiple small diverticula. B, left kidney with large diverticula
mg. per cent) was treated with intravenous glucose and the omphalocele was repaired surgically on the second day. Posterior eventration of the diaphragm was present and malrotation of the gut was suspected radiologically. Excretory urography (IVP) showed caliceal diverticula and normal lower tracts, and the karyotype was normal (fig. 2). A hernia repair was done at 6 months that left the testis tethered in the lower part of the inguinal canal. The patient returned 3 years later for advice on bilateral undescended testes. A repeat IVP showed that the caliceal diverticula had not increased in size proportional to the growth of the kidney, renal function was normal and the urine was sterile. The non-palpable testis was explored and found to be extremely high in position with a short vascular pedicle. After a normal biopsy the testis was autotransplanted successfully using the inferior epigastric vessels. Complete malrotation was present and an incidental
appendectomy was done. Convalescence was uneventful. DISCUSSION
There are several urological issues involved in the management of patients with the Beckwith-Wiedemann syndrome. Screening for tumors should be frequent and should involve all of the viscera, with computerized tomography probably being the tool of choice. Nephroblastomas, when present, should be excised segmentally because of their multifocal origins and the possibility of recurrence. Management of the undescended testis should include biopsy to exclude dysplastic changes. Non-palpable testes usually are high within the abdomen and a transperitoneal approach is recommended. The caliceal diverticula do not appear to impair renal function or become obstructive, requiring observation only.
REFERENCES
J. L.: Hyperplastic fetal visceromegaly with macroglossia, omphalocele, cytomegaly of the adrenal fetal cortex, postnatal somatic gigantism, and other abnormalities: a newly recognized syndrome. Proceedings of the American Pediatric Society, Seattle, Washington, June 16-18, abstract 41, 1964. 2. Wiedemann, H. R.: Complex malformatif familial avec hernie ombilicale et macroglossie-un "syndrome nouveau"? J. Genet. Hum., 13: 223, 1964. 3. Beckwith, J. B.: Macroglossia, omphalocele, adrenal cyclomegaly, gigantism and hyperplastic visceromegaly. Birth Defects, 5: 188, 1. Beckwith, J. B., Wang, C., Donnell, G. N. and Gwinn,
1969.
4. Sotelo-Avila, C. and Gooch, W. M.: Neoplasms associated with the Beckwith-Wiedemann syndrome. Perspect. Ped. Path., 3: 255, 1976. 5. Williams, D. I.: Renal anomalies. In: Urology in Childhood. Berlin: Springer-Verlag, p. 76, 1974. 6. Virdis, R., Drayer, J. I. M., Montoliu, J., Levine, L. S. and Laragh, J. H .. Hypertension and medullary sponge kidneys in an adolescent with Beckwith-Wiedemann syndrome. J. Ped., 91: 761, 1977. 7. Raine, P.A., Noblett, H. R., Houghton-Allen, B. W. and Campbell, P. E.: Breast fibroadenoma and cardiac anomaly associated with EMG (Beckwith-Wiedemann) syndrome. J. Ped., 94: 633, 1979. 8. Ichiba, Y. and Aoyama, K.: Adrenal calcification in BeckwithWiedemann syndrome. Amer. J. Dis. Child., 131: 1296, 1977.
THE JO-U-3.NAL OF UROI,OG-Y
CopyT:ight © 1981 by The V,filifa.rn..s & Vi/ilk.ins Co.
uL 125 1 lviarch
Printed in U.S.A.
UROLOGICAL IIVl:PLICATIONS THE BECKVVITH-\IVIEDEivIANN SYNDROME WILLIAM N. TAYLOR From the Department of Surgery, Section of Urology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina
ABSTRACT
A significant number of children with the Beckwith-Wiedemann syndrome are prone to the development of nephroblastomas and adrenal carcinomas. Renomegaly, a prolonged tubular blush on excretory urography similar to that of medullary sponge kidney, and previously undescribed caliceal diverticula may be observed. Diligent follovvup is mandatory to detect early neoplasia. Suggestions are detailed based on reported case management. The Beckwith-Wiedemann or E.M.G. (exomphalos, macroglossia and gigantism) syndrome is a rare syndrome reported independently by Beckwith and Wiedemann in 1964 and >200 cases subsequently have been reported mainly in the pediatric and pathology literature. 1• 2 In essence, the striking criteria of this syndrome are macroglossia, macrostomia and exomphalos at birth, and hemihypertrophy or gigantism that may develop later. Familial cases believed to be inherited as an autosomal dominant are frequent but many cases are sporadic. No consistent chromosomal defect has been detected and the disease pr-esents in partial forms with some of the stigmas only. Birth
areas of renal blastema formation at the corticomedullary junction that are believed to be potentially oncogenic. 4 The medullary architecture is disorganized, lacks linearity and has increased stroma with fewer collecting ducts, which are dilated.3· 4 Of the patients >10 per cent will suffer neoplasms in early childhood, with Wilms tumor and adrenal carcinoma being predominant.' Other malignant tumors are hepatoblastomas, sarcomas, gonadoblastomas and neural tumors. Radiological features with contrast medium show a prolonged tubular opacification similar to medullary sponge kidney, and not described previously are cystic areas in the forniceal region
Fm. 1. A, typical slit-like earlobe fissure. B, macroglossia and macrostomia
weight usually is greater than the 90th percentile and other features are a flame nevus in the metopic region that fades with time, deep earlobe fissures, diastasis of the recti, undescended testes, cardiac anomalies, malrotation of the bowel and eventration of the diaphragm. Perinatal hypoglycemia makes recognition of this syndrome at birth imperative since it frequently is fatal if untreated. Pathological examination of the kidneys shows excessive lobulation and each kidney weighs 3 to 4 times more than normal. 3 Microscopically, there is increased glomeruloneogenesis, particularly at the inner cortex, and there are discrete Accepted for publication May 9, 1980. 439
suggestive of caliceal diverticula. Similar diverticuJa are evident but not described in the literature. s-s These diverticula are filled easily on retrograde pyelography, are non-obstructive and do not increase in size proportional to renal growth. Neither defect appears to have a deleterious effect on renal function. CASE REPORT
The patient was the third sibling of normal parents, the first 2 dying shortly after birth, presumably of hypoglycemia. Birth weight was 10 pounds 4 ounces. Macroglossia, macrostomia, a
flame nevus in the metopic region, fissures in the earlobes and an undescended testis were present (fig. 1). Hypoglycemia (25
440
TAYLOR
0
RIGHT
QG
(_o (
(\\.\
LEFT Fm. 2. A, right kidney with multiple small diverticula. B, left kidney with large diverticula
mg. per cent) was treated with intravenous glucose and the omphalocele was repaired surgically on the second day. Posterior eventration of the diaphragm was present and malrotation of the gut was suspected radiologically. Excretory urography (IVP) showed caliceal diverticula and normal lower tracts, and the karyotype was normal (fig. 2). A hernia repair was done at 6 months that left the testis tethered in the lower part of the inguinal canal. The patient returned 3 years later for advice on bilateral undescended testes. A repeat IVP showed that the caliceal diverticula had not increased in size proportional to the growth of the kidney, renal function was normal and the urine was sterile. The non-palpable testis was explored and found to be extremely high in position with a short vascular pedicle. After a normal biopsy the testis was autotransplanted successfully using the inferior epigastric vessels. Complete malrotation was present and an incidental
appendectomy was done. Convalescence was uneventful. DISCUSSION
There are several urological issues involved in the management of patients with the Beckwith-Wiedemann syndrome. Screening for tumors should be frequent and should involve all of the viscera, with computerized tomography probably being the tool of choice. Nephroblastomas, when present, should be excised segmentally because of their multifocal origins and the possibility of recurrence. Management of the undescended testis should include biopsy to exclude dysplastic changes. Non-palpable testes usually are high within the abdomen and a transperitoneal approach is recommended. The caliceal diverticula do not appear to impair renal function or become obstructive, requiring observation only.
REFERENCES
J. L.: Hyperplastic fetal visceromegaly with macroglossia, omphalocele, cytomegaly of the adrenal fetal cortex, postnatal somatic gigantism, and other abnormalities: a newly recognized syndrome. Proceedings of the American Pediatric Society, Seattle, Washington, June 16-18, abstract 41, 1964. 2. Wiedemann, H. R.: Complex malformatif familial avec hernie ombilicale et macroglossie-un "syndrome nouveau"? J. Genet. Hum., 13: 223, 1964. 3. Beckwith, J. B.: Macroglossia, omphalocele, adrenal cyclomegaly, gigantism and hyperplastic visceromegaly. Birth Defects, 5: 188, 1. Beckwith, J. B., Wang, C., Donnell, G. N. and Gwinn,
1969.
4. Sotelo-Avila, C. and Gooch, W. M.: Neoplasms associated with the Beckwith-Wiedemann syndrome. Perspect. Ped. Path., 3: 255, 1976. 5. Williams, D. I.: Renal anomalies. In: Urology in Childhood. Berlin: Springer-Verlag, p. 76, 1974. 6. Virdis, R., Drayer, J. I. M., Montoliu, J., Levine, L. S. and Laragh, J. H .. Hypertension and medullary sponge kidneys in an adolescent with Beckwith-Wiedemann syndrome. J. Ped., 91: 761, 1977. 7. Raine, P.A., Noblett, H. R., Houghton-Allen, B. W. and Campbell, P. E.: Breast fibroadenoma and cardiac anomaly associated with EMG (Beckwith-Wiedemann) syndrome. J. Ped., 94: 633, 1979. 8. Ichiba, Y. and Aoyama, K.: Adrenal calcification in BeckwithWiedemann syndrome. Amer. J. Dis. Child., 131: 1296, 1977.