- Email: [email protected]
Familial occurrence of undescended testes
FAMILIAL M. SAVION,
OCCURRENCE
OF UNDESCENDED
TESTES
M.D.
I. NISSENKORN, C. SERVADIO,
M.D. M.D.
Z. DICKERMAN,
M.D.
From the Department of Urology and Institute of Juvenile and Adolescent Endocrinology, Beilinson Medical Center, Petah Tiqva, and Tel Aviv University Sackler School of Medicine, Israel
ABSTRACTWe had the opportunity of treating a family with 6 siblings, 2 of them twins, all sons of the same father and mother, 5 of whom had undescended testes. We hereby report on this rare occurrence offamilial undescended testes. Only 1 similar case was previously reported in the English literature. The literature is reviewed, and possible etiologic factors are mentioned.
The occurrence of undescended testes in more than one member of the same family is a matter of unof repeated record, 1-4but the occurrence descended testes in 5 members of the same family is rare. To the best of our knowledge this is an unusual instance, and only 1 similar case reported in 1922 in which 6 brothers had such an abnormality.5 Material
and Methods
The findings before and after the operation had been collected from the patients’ records in our hospital. In addition to anamnestic history and physical examination, the investigation included: sex chromatin determination, hormonal evaluation including: the blood levels of follicular stimulating hormone (FSH) and luteinizing hormone (LH), and the size of the testes measured with orchidometer (Tables I and II). Two of the sons underwent ultrasound examination of the urinary tract to find accompanying anomalies in the urinary system. Three of the sons had been treated with HCG a few months before the operation without evident results. The postoperative follow-up was between one to five years. The boys had been checked every six months, and special attention had been given to the form and size of the testes which had been operated on, the secondary sex signs, and the child’s development.
UROLOGY
/ APRIL
1984
/ VOLUME
XXIII,
NUMBER 4
In the family are 6 boys of the same nonconsanguineous parents whose family histories are indefinite. The father, thirty-seven-years’ old, was born in Israel and had been operated on at age eleven years for left inguinal hernia. Until he was ten years’ old he had a left mobile testis. The father does not remember any inguinal surgery of his brothers or other relatives, but is rather uncertain about this. The mother is thirty-five years’ old and was born in Yemen. She had no miscarriages or stillbirths but had short menses. There are 6 children, all boys. Case Reports Case 1 (13 yr, 6 mo) Findings on physical examination were normal except for congenital deafness in the right ear and left varicocele. The left undescended testis (UT) had been palpated in the left inguinal canal, and the right testis was mobile. The size of the UT was 2 ml and the mobile testis (MT) 1.5 ml; the length of the penis was 5.5 cm. The scrotum was hypoplastic. The blood levels of FSH and LH were normal; sex chromatin was normal. The ultrasound examination of the urinary system disclosed no pathology. He had not received HCG before he underwent left orchiopexy at age nine years. At follow-up examination the right testis was
TABLE
Age at Operation Case
(yr)
1
Size of Testes
Lt, UT Rt,
10
3 4
5 2
5
3
KEY: UT
Rt
Lt
Length of Penis (cm)
Rt. ear deafness and It. varicocele . .
1.5
2
5.5
1.5
2
6.5
9 Lt. inguinal hernia . .
2 1.5
2 1.5
?
?
Side and Pathology
9
2
in
I. Findings on physical examination 5 brothers with undescended testes
MT
Rt, UT Lt, MT Bilat, UT Lt, PT
= undexended
Rt, UT Lt, MT testis; MT
Other Pathology
(ml)
5 ? 5.2
= mobile testis, PT = perineal testis.
normal, the left testis was smaller; penis and scrotum were normal.
TABLE II.
follow-up
Laboratory findings and time of in 5 brothers with undescended testes
Sex
Case 2 (age 12 yr) Case
Chrom. (%)
FSH and LH (mu/ml)
HCG Treatment
Follow-Up
Findings on physical examination showed normal development; right UT had been palpated in right inguinal canal, and the left testis was mobile. The size of the right testis was 1.5 ml and the left 2 ml. The length of the penis was 6.5 cm. The right hemiscrotum was hypoplastic. The sex chromatin and the blood gonadotropin (CT) level were normal. The boy had received 500 units of HCG twice weekly for five weeks, unsuccessfully, and at age ten right orchiopexy was performed. Follow-up showed the child to be well developed; the testes were normal in size and consistency.
of HCG twice weekly for five weeks were given but without results. At age two years, left orchiopexy had been performed.
Case 3 (age 10 yr, 6 mo)
Case 5 (age 3 yr, 6 mo)
Findings on general physical examination were normal except for bilateral UT. Both testes had been palpated in the inguinal canals and measured 2 ml each. The length of the penis was 5 cm, and the scrotum was small and symmetric. Sex chromatin was normal. GT blood level had not been checked. The boy did not receive hormonal therapy At age five years, he underwent right orchiopexy and at age eight years, left orchiopexy. Findings on follow-up examinations were normal.
This boy is a twin, not identical, to Case 4. Findings on physical examination were normal except for right UT, which had been palpated in right inguinal canal, and left mobile testis. Measurement of both testes was normal; the penis length was 5.2 cm and the scrotum hypoplastic. Sex chromatin and GT blood level were normal. The boy had been treated with 500 units of HCG twice weekly for five weeks unsuccessfully. At age three years right orchiopexy had been performed.
Case 4 (age 3 yr, 6 mo)
Case 6 (age 8 yr)
Findings on physical examination were normal except for left ectopic perineal testis and left inguinal hernia. The size of the testes was 1.5 ml, each. Size of penis and the sex chromatin were normal. GT blood level had not been checked. Ultrasound examination of the urinary system was normal. Five hundred units
This well-developed child had normal findings on physical examination, including genitalia.
356
1 2
0 0
3 4
0 1
5
0
1.39 0.40
1.47 0.20 NP’ NP
1.27
1.52
None 500 U x 2/wk for 5 wk None 500 U x 2/wk for 5 wk 500U x 2/wk for 5 wk
(yr) 4’12 2 5’12 I’/2
1
NP = not performed.
Comment An empty scrotum may be the result of retractile, ectopic, or truly undescended testicles.
UROLOGY
/ APRIL 1984
/ VOLUME XXIII, NUMBER 4
About one half of the patients referred to the consultant as having undescended testes will, in fact, have retractile testes. These testes readily retract from the scrotum into the superficial inguinal pouch presumably because of a protective reflex which is most prominent during childhood. Ectopic testes are those which descend to the wrong area. The most common type lodge in the superficial inguinal pouch.6 The true cryptorchid testis is arrested in the pathway of its normal descent, anywhere from an intraabdominal position within the peritoneal cavity, to a position just distal to the external inguinal ring. Undescended testes are unilateral in at least 75 per cent of patients. The high scrotal testis is generally assumed to be abnormal and is treated as an undescended testis.7 In the family described we had 4 patients with unilateral and 1 with bilateral undestended testes. There is no doubt that in this family all 5 sons had undescended testes which required operation. Unfortunately, the 2 oldest sons had been operated on late (at 9 and 10 years of age) because the parents paid little attention to the problem. It is known that the right undescended testes are more frequently involved than the left and that in up to 3 per cent of the patients a unilateral absent testis occursr8 Superficial inguinal ectopia may account for as many as 60 per cent of all cryptorchid testes.e In our reported family there was no absent testis, and superficial inguinal ectopia had been found in 5 of 6, 83 per cent, cryptorchid testes. One child has an ectopic perineal testis. Genetic factors may play a role in patients with undescended testes since maldescendence can be both familial and inherited.4J0 The possibility that UT may be inherited arose when it recurred in several generations of the same families. In 1975 Pardo-Mindan et al. l reported on three such families. In the first family, the father, his twin three-year-old sons, and their six-year-old sibling had undescended left testes. In the second, cryptorchism on the left side occurred in the father, his brother, and the brother’s seven-year-old son. In the third family, twin brothers, two years of age, had cryptorchism on the left side. Rezvani, Rettig, and DiGeorge2 reported two half-brothers with cryptorchism on the right side who had different fathers. Reportedly the mother’s father and one of her paternal uncles also had unilateral undescended testes.
UROLOGY
/ APRIL
1984
/ VOLUME
XXIII,
NUMBER 4
There was no history of cryptorchism in the 3 brothers of the mother, but 1 of her sisters also had a three-year-old boy with a unilaterally undescended testis. The testes of the half-brother failed to descend following a short course of therapy with HCG (a total dose of 20,000 units). In the family reported by us the father did not remember any of his brothers or other relatives having undergone inguinal surgery. The effectiveness of HCG in the treatment of undescended testes has been known for many years and is compatible with current theories on the etiology of undescended testes. Ehrlich et al.” reported in 1969 that gonadotropin therapy resulted in the descent of 81 of 350 undescended testes. Therapy was more effective for bilateral than for unilateral undescended testes. The best results were obtained in children between the ages of two and five years. Nevertheless, it is commonly believed that it is inadvisable to treat unilateral cryptorchism with hormonal therapy, since any stimulus present in early life has had the opportunity to act on both testes. In our reported family 3 of the 5 patients were treated with a total course of 5,000 units of HCG with no positive results and even in the bilateral undescended testes one of the testes did not descend into the scrotum. In the family described by Corbus and 0’Conor5 all 6 boys of the 8 siblings had undescended testes, including 2 bilateral, 2 on the right side, and 2 on the left side. Perrett and O’Rourke4 reported on 3 brothers with cryptorchism on the right side and a fourth normal sibling. They also reported unilateral undescended testis in 8 of the 18 male subjects in four generations of the same family. They were able to trace the trait through four generations in that family and concluded that inheritance was by dominant gene with limited penetrance. The incidence of cryptorchism is known to be increased in certain genetically transmitted disorders including cystic fibrosis, oculocerebrorenal syndrome of Lowe, and in some not so well-recognized syndromes. l2 Minehan and Touloukian3 reported 3 brothers, aged thirteen, eleven, and seven years, with maldescent of the right testis. Intravenous urography was performed in each case and was normal. There was no history of the trait in the father’s or mother’s family for the preceding two generations. The authors believe that this family transmits the trait genetically as a sex-linked or dominant characteristic.
357
In our reported family 5 boys of the 6 siblings had undescended testes including 1 bilateral, 2 on the right side, and 2 on the left side. Ultrasound of the urinary system was performed in 2 and was normal. We did not receive a history of the trait in the father’s or mother’s family for the preceding generations. We believe that this family transmits the trait genetically as a sexlinked or dominant gene with limited penetrance. Department of Urology Beilinson Medical Center Petah Tiqva, Israel (DR. NISSENKORN) References 1.
Pardo-Mindan FJ, Vargas TF, Garcia JG, and Virto RMT: Familial cryptorchidism, Pediatrics 56: 616 (1975).
358
2. Rezvani I, Rettig KR, and DiGeorge AM: Inheritance of cryptorchidism, ibid 58: 774 (1976). 3. Minehan T, and Touloukian R: Cryptorchidism in siblings. ibid 53: 770 (1974). 4. Perrett LJ, and O’Rourke DA: Hereditary cryptorchidism, Med J Aust 25: 1289 (1969). 5. Corbus BC, and O’Conor VJ: The familial occurrence of undescended testes, Surg Gynecol Obstet 34: 237 (1922). 6. Browne D: Treatment of undescended testicle, Proc R Sot Med 42: 643 (1949). 7. Shapiro SR, and Bodai BI: Current concepts of the undestended testis, Surg Gynecol Obstet 147: 617 (1978). 8. Gross RE, and Jewett TC Jr: Surgical experience from 1,222 operations for undescended testes, JAMA 160: 634 (1956). 9. Kelalis PP, King LR, and Belman AB: Clinic Pediatric Urology, Philadelphia, W. B. Saunders Co. 1976, p 655. 10. Abrams HJ: Familial cryptorchidism. Urology 5: 849 (1975). 11. Ehrlich RM, et al: Effect of gonadotropin in cryptorchidism, J Urol 102: 793 (1969). 12. Insley J: Syndrome associated with a deficiency of part of the long arm of chromosome no. 18, Arch Dis Child 42: 140 (1967).
UROLOGY
/ APRIL 1984
! VOLUME
XXIII.
NUMBER
4
OCCURRENCE
OF UNDESCENDED
TESTES
M.D.
I. NISSENKORN, C. SERVADIO,
M.D. M.D.
Z. DICKERMAN,
M.D.
From the Department of Urology and Institute of Juvenile and Adolescent Endocrinology, Beilinson Medical Center, Petah Tiqva, and Tel Aviv University Sackler School of Medicine, Israel
ABSTRACTWe had the opportunity of treating a family with 6 siblings, 2 of them twins, all sons of the same father and mother, 5 of whom had undescended testes. We hereby report on this rare occurrence offamilial undescended testes. Only 1 similar case was previously reported in the English literature. The literature is reviewed, and possible etiologic factors are mentioned.
The occurrence of undescended testes in more than one member of the same family is a matter of unof repeated record, 1-4but the occurrence descended testes in 5 members of the same family is rare. To the best of our knowledge this is an unusual instance, and only 1 similar case reported in 1922 in which 6 brothers had such an abnormality.5 Material
and Methods
The findings before and after the operation had been collected from the patients’ records in our hospital. In addition to anamnestic history and physical examination, the investigation included: sex chromatin determination, hormonal evaluation including: the blood levels of follicular stimulating hormone (FSH) and luteinizing hormone (LH), and the size of the testes measured with orchidometer (Tables I and II). Two of the sons underwent ultrasound examination of the urinary tract to find accompanying anomalies in the urinary system. Three of the sons had been treated with HCG a few months before the operation without evident results. The postoperative follow-up was between one to five years. The boys had been checked every six months, and special attention had been given to the form and size of the testes which had been operated on, the secondary sex signs, and the child’s development.
UROLOGY
/ APRIL
1984
/ VOLUME
XXIII,
NUMBER 4
In the family are 6 boys of the same nonconsanguineous parents whose family histories are indefinite. The father, thirty-seven-years’ old, was born in Israel and had been operated on at age eleven years for left inguinal hernia. Until he was ten years’ old he had a left mobile testis. The father does not remember any inguinal surgery of his brothers or other relatives, but is rather uncertain about this. The mother is thirty-five years’ old and was born in Yemen. She had no miscarriages or stillbirths but had short menses. There are 6 children, all boys. Case Reports Case 1 (13 yr, 6 mo) Findings on physical examination were normal except for congenital deafness in the right ear and left varicocele. The left undescended testis (UT) had been palpated in the left inguinal canal, and the right testis was mobile. The size of the UT was 2 ml and the mobile testis (MT) 1.5 ml; the length of the penis was 5.5 cm. The scrotum was hypoplastic. The blood levels of FSH and LH were normal; sex chromatin was normal. The ultrasound examination of the urinary system disclosed no pathology. He had not received HCG before he underwent left orchiopexy at age nine years. At follow-up examination the right testis was
TABLE
Age at Operation Case
(yr)
1
Size of Testes
Lt, UT Rt,
10
3 4
5 2
5
3
KEY: UT
Rt
Lt
Length of Penis (cm)
Rt. ear deafness and It. varicocele . .
1.5
2
5.5
1.5
2
6.5
9 Lt. inguinal hernia . .
2 1.5
2 1.5
?
?
Side and Pathology
9
2
in
I. Findings on physical examination 5 brothers with undescended testes
MT
Rt, UT Lt, MT Bilat, UT Lt, PT
= undexended
Rt, UT Lt, MT testis; MT
Other Pathology
(ml)
5 ? 5.2
= mobile testis, PT = perineal testis.
normal, the left testis was smaller; penis and scrotum were normal.
TABLE II.
follow-up
Laboratory findings and time of in 5 brothers with undescended testes
Sex
Case 2 (age 12 yr) Case
Chrom. (%)
FSH and LH (mu/ml)
HCG Treatment
Follow-Up
Findings on physical examination showed normal development; right UT had been palpated in right inguinal canal, and the left testis was mobile. The size of the right testis was 1.5 ml and the left 2 ml. The length of the penis was 6.5 cm. The right hemiscrotum was hypoplastic. The sex chromatin and the blood gonadotropin (CT) level were normal. The boy had received 500 units of HCG twice weekly for five weeks, unsuccessfully, and at age ten right orchiopexy was performed. Follow-up showed the child to be well developed; the testes were normal in size and consistency.
of HCG twice weekly for five weeks were given but without results. At age two years, left orchiopexy had been performed.
Case 3 (age 10 yr, 6 mo)
Case 5 (age 3 yr, 6 mo)
Findings on general physical examination were normal except for bilateral UT. Both testes had been palpated in the inguinal canals and measured 2 ml each. The length of the penis was 5 cm, and the scrotum was small and symmetric. Sex chromatin was normal. GT blood level had not been checked. The boy did not receive hormonal therapy At age five years, he underwent right orchiopexy and at age eight years, left orchiopexy. Findings on follow-up examinations were normal.
This boy is a twin, not identical, to Case 4. Findings on physical examination were normal except for right UT, which had been palpated in right inguinal canal, and left mobile testis. Measurement of both testes was normal; the penis length was 5.2 cm and the scrotum hypoplastic. Sex chromatin and GT blood level were normal. The boy had been treated with 500 units of HCG twice weekly for five weeks unsuccessfully. At age three years right orchiopexy had been performed.
Case 4 (age 3 yr, 6 mo)
Case 6 (age 8 yr)
Findings on physical examination were normal except for left ectopic perineal testis and left inguinal hernia. The size of the testes was 1.5 ml, each. Size of penis and the sex chromatin were normal. GT blood level had not been checked. Ultrasound examination of the urinary system was normal. Five hundred units
This well-developed child had normal findings on physical examination, including genitalia.
356
1 2
0 0
3 4
0 1
5
0
1.39 0.40
1.47 0.20 NP’ NP
1.27
1.52
None 500 U x 2/wk for 5 wk None 500 U x 2/wk for 5 wk 500U x 2/wk for 5 wk
(yr) 4’12 2 5’12 I’/2
1
NP = not performed.
Comment An empty scrotum may be the result of retractile, ectopic, or truly undescended testicles.
UROLOGY
/ APRIL 1984
/ VOLUME XXIII, NUMBER 4
About one half of the patients referred to the consultant as having undescended testes will, in fact, have retractile testes. These testes readily retract from the scrotum into the superficial inguinal pouch presumably because of a protective reflex which is most prominent during childhood. Ectopic testes are those which descend to the wrong area. The most common type lodge in the superficial inguinal pouch.6 The true cryptorchid testis is arrested in the pathway of its normal descent, anywhere from an intraabdominal position within the peritoneal cavity, to a position just distal to the external inguinal ring. Undescended testes are unilateral in at least 75 per cent of patients. The high scrotal testis is generally assumed to be abnormal and is treated as an undescended testis.7 In the family described we had 4 patients with unilateral and 1 with bilateral undestended testes. There is no doubt that in this family all 5 sons had undescended testes which required operation. Unfortunately, the 2 oldest sons had been operated on late (at 9 and 10 years of age) because the parents paid little attention to the problem. It is known that the right undescended testes are more frequently involved than the left and that in up to 3 per cent of the patients a unilateral absent testis occursr8 Superficial inguinal ectopia may account for as many as 60 per cent of all cryptorchid testes.e In our reported family there was no absent testis, and superficial inguinal ectopia had been found in 5 of 6, 83 per cent, cryptorchid testes. One child has an ectopic perineal testis. Genetic factors may play a role in patients with undescended testes since maldescendence can be both familial and inherited.4J0 The possibility that UT may be inherited arose when it recurred in several generations of the same families. In 1975 Pardo-Mindan et al. l reported on three such families. In the first family, the father, his twin three-year-old sons, and their six-year-old sibling had undescended left testes. In the second, cryptorchism on the left side occurred in the father, his brother, and the brother’s seven-year-old son. In the third family, twin brothers, two years of age, had cryptorchism on the left side. Rezvani, Rettig, and DiGeorge2 reported two half-brothers with cryptorchism on the right side who had different fathers. Reportedly the mother’s father and one of her paternal uncles also had unilateral undescended testes.
UROLOGY
/ APRIL
1984
/ VOLUME
XXIII,
NUMBER 4
There was no history of cryptorchism in the 3 brothers of the mother, but 1 of her sisters also had a three-year-old boy with a unilaterally undescended testis. The testes of the half-brother failed to descend following a short course of therapy with HCG (a total dose of 20,000 units). In the family reported by us the father did not remember any of his brothers or other relatives having undergone inguinal surgery. The effectiveness of HCG in the treatment of undescended testes has been known for many years and is compatible with current theories on the etiology of undescended testes. Ehrlich et al.” reported in 1969 that gonadotropin therapy resulted in the descent of 81 of 350 undescended testes. Therapy was more effective for bilateral than for unilateral undescended testes. The best results were obtained in children between the ages of two and five years. Nevertheless, it is commonly believed that it is inadvisable to treat unilateral cryptorchism with hormonal therapy, since any stimulus present in early life has had the opportunity to act on both testes. In our reported family 3 of the 5 patients were treated with a total course of 5,000 units of HCG with no positive results and even in the bilateral undescended testes one of the testes did not descend into the scrotum. In the family described by Corbus and 0’Conor5 all 6 boys of the 8 siblings had undescended testes, including 2 bilateral, 2 on the right side, and 2 on the left side. Perrett and O’Rourke4 reported on 3 brothers with cryptorchism on the right side and a fourth normal sibling. They also reported unilateral undescended testis in 8 of the 18 male subjects in four generations of the same family. They were able to trace the trait through four generations in that family and concluded that inheritance was by dominant gene with limited penetrance. The incidence of cryptorchism is known to be increased in certain genetically transmitted disorders including cystic fibrosis, oculocerebrorenal syndrome of Lowe, and in some not so well-recognized syndromes. l2 Minehan and Touloukian3 reported 3 brothers, aged thirteen, eleven, and seven years, with maldescent of the right testis. Intravenous urography was performed in each case and was normal. There was no history of the trait in the father’s or mother’s family for the preceding two generations. The authors believe that this family transmits the trait genetically as a sex-linked or dominant characteristic.
357
In our reported family 5 boys of the 6 siblings had undescended testes including 1 bilateral, 2 on the right side, and 2 on the left side. Ultrasound of the urinary system was performed in 2 and was normal. We did not receive a history of the trait in the father’s or mother’s family for the preceding generations. We believe that this family transmits the trait genetically as a sexlinked or dominant gene with limited penetrance. Department of Urology Beilinson Medical Center Petah Tiqva, Israel (DR. NISSENKORN) References 1.
Pardo-Mindan FJ, Vargas TF, Garcia JG, and Virto RMT: Familial cryptorchidism, Pediatrics 56: 616 (1975).
358
2. Rezvani I, Rettig KR, and DiGeorge AM: Inheritance of cryptorchidism, ibid 58: 774 (1976). 3. Minehan T, and Touloukian R: Cryptorchidism in siblings. ibid 53: 770 (1974). 4. Perrett LJ, and O’Rourke DA: Hereditary cryptorchidism, Med J Aust 25: 1289 (1969). 5. Corbus BC, and O’Conor VJ: The familial occurrence of undescended testes, Surg Gynecol Obstet 34: 237 (1922). 6. Browne D: Treatment of undescended testicle, Proc R Sot Med 42: 643 (1949). 7. Shapiro SR, and Bodai BI: Current concepts of the undestended testis, Surg Gynecol Obstet 147: 617 (1978). 8. Gross RE, and Jewett TC Jr: Surgical experience from 1,222 operations for undescended testes, JAMA 160: 634 (1956). 9. Kelalis PP, King LR, and Belman AB: Clinic Pediatric Urology, Philadelphia, W. B. Saunders Co. 1976, p 655. 10. Abrams HJ: Familial cryptorchidism. Urology 5: 849 (1975). 11. Ehrlich RM, et al: Effect of gonadotropin in cryptorchidism, J Urol 102: 793 (1969). 12. Insley J: Syndrome associated with a deficiency of part of the long arm of chromosome no. 18, Arch Dis Child 42: 140 (1967).
UROLOGY
/ APRIL 1984
! VOLUME
XXIII.
NUMBER
4