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Familial Incidence of Cryptorchidism
0022-5347 /81/1266-0508$02.00/0 Vol. 127, March
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1982 by The Williams & Wilkins Co.
FAMILIAL INCIDENCE OF CRYPTORCHIDISM I. R. G. JONES
AND
I. D. YOUNG
From the Departments of Pediatric Surgery and Medicine, University Hospital of Wales, Heath Park, Cardiff, United Kingdom
ABSTRACT
Isolated family reports and larger epidemiological studies suggest that hereditary factors are involved in cryptorchidism. We analyzed pedigrees from the families of 51 boys treated for cryptorchidism. The data are consistent with multifactorial inheritance with an incidence of 9. 75 per cent in siblings. A plea is made that male siblings should be assessed when this condition is ascertained. TABLE 1. The incidence of cryptorchidism in first and second
Although cryptorchidism is a relatively common condition the underlying cause remains obscure. Several isolated families have been reported in which a strong family history exists 1- 3 and 2 large surveys also suggest that familial factors may have an important etiological role. 4 • 5 Recent inquiries from interested parents concerning the risk in future children prompted us to discover that the literature on this subject is sparse. Herein we discuss the nature of those genetic factors that may be etiologically involved in cryptorchidism and also the suitable recurrence risks.
degree male relatives
First degree: Fathers Siblings Totals Second degree: Paternal uncles Maternal uncles Nephews and half siblings Totals
SUBJECTS AND METHODS
Cooperation was sought from the parents of boys admitted to our hospital for orchiopexy during a 2-year period. Because of the potentially embarrassing nature of this condition, no further attempt was made to contact the family if they failed to respond to an introductory letter on 2 occasions. For those who agreed a full family pedigree was constructed to include all first and second degree male relatives. The operative notes of all probands were examined and in those cases when a positive family history was elicited original hospital records were consulted. RESULTS
Information was obtained from 51 of 77 families. Of those not included in the study 16 families failed to reply, 9 families refused to assist and 1 child was adopted. The incidence of cryptorchidism in first and second degree male relatives is shown in table 1. Frequently, no information concerning the grandfathers of the probands could be obtained and they have not been included in the analysis. In table 2 the side of involvement in the probands and in their affected relatives is shown. The mean paternal age at birth for the 39 isolated cases was 29.16 years, compared to 29.65 years for the 12 cases with a positive family history and 28.59 years for all births in England and Wales in 1972,6 the modal year of birth of the pro bands in the study. These differences are not statistically significant. There was no consanguinity among the parents of the probands. DISCUSSION
The 3 recognized modes of inheritance are chromosomal, mendelian and multifactorial. Chromosomal studies in cryptorchidism have proved unrewarding. 7• 8 No clear pattern of mendelian inheritance emerged in pedigree analysis. X-linkage was excluded by 2 examples of male-to-male transmission and a roughly equal incidence in maternal and paternal uncles. The absence of a paternal age effect and consanguinity in the parents of the probands militates against autosomal dominant and recessive inheritance, respectively. In multifactorial inheritance the frequency among first degree relatives is approximately equal to Jq, where q is the frequency
Totals
Affected No.(%)
51 41 92
2 (3.9) 4 (9.75) 6 (6.5)
74 61 6 141
3 (4) 4 (6.6)
QJQL_ 7 (5)
TABLE 2. Data subdivided on basis of laterality Side Affected in Proband Rt. Lt. Bilat. Totals
First Degree Relatives
Second Degree Relatives
Affected
No.
Affected Totals
Rt.
Lt.
Bilat.
Unknown
Totals
Rt. 37 30 25
0 0 0
1 0 0
1 0 2
1 2 0
39 43 59
92
0
1
3
3
141
Lt. Bilat.
17 18 16
2 1 0
0 1 1
51
3
2
0 1 0
in the general population. 9 If we assume that q = 0.008 10 then the expected incidence in first degree relatives equals ~0.008 = 8.9 per cent, which compares favorably to the observed incidence of 6.5 per cent found in this study. Similarly, the expected relative frequency in siblings equals 1 Jq for a multifactorial trait, giving an expected relative frequency of 11.24 as compared to an observed value of 12.19 obtained for siblings in this study. Thus, these data are consistent with multifactorial inheritance. One cautionary note concerns the demonstration of heterogeneity in cryptorchidism on the basis of pathological 11 and endocrine studies, 12 and it is possible that genetic heterogeneity also may be implicated in this condition. Whatever the precise genetic mechanism involved in the genesis of cryptorchidism, there is little dispute that its detection and connection are important in view of the increased risks of sterility, torsion, injury and malignant change. The high incidence in siblings prompts us to alert those clinicians who treat cryptorchidism to pay particular attention to the family of such patients. Mr. J. Lari allowed us to study his patients and Dr. P. S. Harper assisted in the preparation of the manuscript. REFERENCES
1. Abrams, H.J.: Familial cryptorchidism. Letter to the Editor. Urol-
ogy, 5: 849, 1975. 2. Rezvani, I., Rettig, K. R. and DiGeorge, A. M.: Inheritance of cryptorchidism. Letter to the Editor. Pediatrics, 58: 774, 1976. 3. Perrett, L. J. and O'Rourke, D. A.: Hereditary cryptorchidism.
Accepted for publication February 27, 1981. 508
FAMILIAL INCIDENCE OF CRYPTORCHIDISM
Med. J. Aust., 1: 1289, 1969. 4. Scorer, C. G. and Farrington, G. H.: Congenital Deformities of the Testis and Epididymis. New York: Appleton-Century-Crofts, p. 41, 1971. 5. Waaler, P. E.: Clinical and cytogenetic studies in undescended testes. Acta Paed. Scand., 65: 553, 1976. 6. The Registrar General's Statistical Review of England and Wales for the year 1972. London: Her Majesty's Stationery Office, 1974. 7. Dewald, G. W., Kelalis, P. P. and Gordon, H.: Chromosomal studies in cryptorchidism. J. Urol., 117: llO, 1977.
509
8. Klugo, R., Van Dyke, D. L. and Weiss, L.: Cytogenetic studies of cryptorchid testes. Urology, 11: 255, 1978. 9. Edwards, J. H.: The simulation of mendelism. Acta Genet., 10: 63, 1960. 10. Mitchell, R. G.: Paediatric aspects of cryptorchidism and hypogonadism. Dev. Med. Child. Neurol., 19: 673, 1977. 11. Pardo-Mindan, F. J.: Cryptorchidism. Lancet, 1: 1345, 1974. 12. Battin, J. and Colle, M.: Heterogeneite du syndrome 'cryptorchidie.' Edute de la reserve hypophysaire en gonadotropines chez 50 enfants cryptorchides nonpuberes. Arch. Fr. Ped., 34: 595, 1977.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1982 by The Williams & Wilkins Co.
FAMILIAL INCIDENCE OF CRYPTORCHIDISM I. R. G. JONES
AND
I. D. YOUNG
From the Departments of Pediatric Surgery and Medicine, University Hospital of Wales, Heath Park, Cardiff, United Kingdom
ABSTRACT
Isolated family reports and larger epidemiological studies suggest that hereditary factors are involved in cryptorchidism. We analyzed pedigrees from the families of 51 boys treated for cryptorchidism. The data are consistent with multifactorial inheritance with an incidence of 9. 75 per cent in siblings. A plea is made that male siblings should be assessed when this condition is ascertained. TABLE 1. The incidence of cryptorchidism in first and second
Although cryptorchidism is a relatively common condition the underlying cause remains obscure. Several isolated families have been reported in which a strong family history exists 1- 3 and 2 large surveys also suggest that familial factors may have an important etiological role. 4 • 5 Recent inquiries from interested parents concerning the risk in future children prompted us to discover that the literature on this subject is sparse. Herein we discuss the nature of those genetic factors that may be etiologically involved in cryptorchidism and also the suitable recurrence risks.
degree male relatives
First degree: Fathers Siblings Totals Second degree: Paternal uncles Maternal uncles Nephews and half siblings Totals
SUBJECTS AND METHODS
Cooperation was sought from the parents of boys admitted to our hospital for orchiopexy during a 2-year period. Because of the potentially embarrassing nature of this condition, no further attempt was made to contact the family if they failed to respond to an introductory letter on 2 occasions. For those who agreed a full family pedigree was constructed to include all first and second degree male relatives. The operative notes of all probands were examined and in those cases when a positive family history was elicited original hospital records were consulted. RESULTS
Information was obtained from 51 of 77 families. Of those not included in the study 16 families failed to reply, 9 families refused to assist and 1 child was adopted. The incidence of cryptorchidism in first and second degree male relatives is shown in table 1. Frequently, no information concerning the grandfathers of the probands could be obtained and they have not been included in the analysis. In table 2 the side of involvement in the probands and in their affected relatives is shown. The mean paternal age at birth for the 39 isolated cases was 29.16 years, compared to 29.65 years for the 12 cases with a positive family history and 28.59 years for all births in England and Wales in 1972,6 the modal year of birth of the pro bands in the study. These differences are not statistically significant. There was no consanguinity among the parents of the probands. DISCUSSION
The 3 recognized modes of inheritance are chromosomal, mendelian and multifactorial. Chromosomal studies in cryptorchidism have proved unrewarding. 7• 8 No clear pattern of mendelian inheritance emerged in pedigree analysis. X-linkage was excluded by 2 examples of male-to-male transmission and a roughly equal incidence in maternal and paternal uncles. The absence of a paternal age effect and consanguinity in the parents of the probands militates against autosomal dominant and recessive inheritance, respectively. In multifactorial inheritance the frequency among first degree relatives is approximately equal to Jq, where q is the frequency
Totals
Affected No.(%)
51 41 92
2 (3.9) 4 (9.75) 6 (6.5)
74 61 6 141
3 (4) 4 (6.6)
QJQL_ 7 (5)
TABLE 2. Data subdivided on basis of laterality Side Affected in Proband Rt. Lt. Bilat. Totals
First Degree Relatives
Second Degree Relatives
Affected
No.
Affected Totals
Rt.
Lt.
Bilat.
Unknown
Totals
Rt. 37 30 25
0 0 0
1 0 0
1 0 2
1 2 0
39 43 59
92
0
1
3
3
141
Lt. Bilat.
17 18 16
2 1 0
0 1 1
51
3
2
0 1 0
in the general population. 9 If we assume that q = 0.008 10 then the expected incidence in first degree relatives equals ~0.008 = 8.9 per cent, which compares favorably to the observed incidence of 6.5 per cent found in this study. Similarly, the expected relative frequency in siblings equals 1 Jq for a multifactorial trait, giving an expected relative frequency of 11.24 as compared to an observed value of 12.19 obtained for siblings in this study. Thus, these data are consistent with multifactorial inheritance. One cautionary note concerns the demonstration of heterogeneity in cryptorchidism on the basis of pathological 11 and endocrine studies, 12 and it is possible that genetic heterogeneity also may be implicated in this condition. Whatever the precise genetic mechanism involved in the genesis of cryptorchidism, there is little dispute that its detection and connection are important in view of the increased risks of sterility, torsion, injury and malignant change. The high incidence in siblings prompts us to alert those clinicians who treat cryptorchidism to pay particular attention to the family of such patients. Mr. J. Lari allowed us to study his patients and Dr. P. S. Harper assisted in the preparation of the manuscript. REFERENCES
1. Abrams, H.J.: Familial cryptorchidism. Letter to the Editor. Urol-
ogy, 5: 849, 1975. 2. Rezvani, I., Rettig, K. R. and DiGeorge, A. M.: Inheritance of cryptorchidism. Letter to the Editor. Pediatrics, 58: 774, 1976. 3. Perrett, L. J. and O'Rourke, D. A.: Hereditary cryptorchidism.
Accepted for publication February 27, 1981. 508
FAMILIAL INCIDENCE OF CRYPTORCHIDISM
Med. J. Aust., 1: 1289, 1969. 4. Scorer, C. G. and Farrington, G. H.: Congenital Deformities of the Testis and Epididymis. New York: Appleton-Century-Crofts, p. 41, 1971. 5. Waaler, P. E.: Clinical and cytogenetic studies in undescended testes. Acta Paed. Scand., 65: 553, 1976. 6. The Registrar General's Statistical Review of England and Wales for the year 1972. London: Her Majesty's Stationery Office, 1974. 7. Dewald, G. W., Kelalis, P. P. and Gordon, H.: Chromosomal studies in cryptorchidism. J. Urol., 117: llO, 1977.
509
8. Klugo, R., Van Dyke, D. L. and Weiss, L.: Cytogenetic studies of cryptorchid testes. Urology, 11: 255, 1978. 9. Edwards, J. H.: The simulation of mendelism. Acta Genet., 10: 63, 1960. 10. Mitchell, R. G.: Paediatric aspects of cryptorchidism and hypogonadism. Dev. Med. Child. Neurol., 19: 673, 1977. 11. Pardo-Mindan, F. J.: Cryptorchidism. Lancet, 1: 1345, 1974. 12. Battin, J. and Colle, M.: Heterogeneite du syndrome 'cryptorchidie.' Edute de la reserve hypophysaire en gonadotropines chez 50 enfants cryptorchides nonpuberes. Arch. Fr. Ped., 34: 595, 1977.