Pediatr Surg Int (2014) 30:733–736 DOI 10.1007/s00383-014-3522-x
ORIGINAL ARTICLE
Congenital absence of the vas deferens and unilateral renal agenesis: implications for patient and family Victoria Alison Lane • Simon Scammell Noreen West • Govind V. Murthi
•
Accepted: 22 May 2014 / Published online: 31 May 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Background and aims At routine groin surgery in male paediatric patients occasionally the vas deferens may be absent. This finding usually leads to investigations to establish the status of the contralateral vas deferens and the status of the kidneys. It is not uncommon to find either an ipsilateral renal agenesis or congenital bilateral absence of the vas deferens. The latter finding prompts a test for cystic fibrosis. We report three patients who upon investigation were found to have the rare combination of congenital bilateral absence of the vas deferens and unilateral renal agenesis, and discuss the possible embryological basis, the clinical management and the long-term implications of these findings. Patients and methods We present three patients who were incidentally found to have absence of the vas deferens whilst undergoing elective groin surgery and following further tests were diagnosed with congenital bilateral absence of the vas deferens and unilateral renal agenesis. The case notes were reviewed, together with the results of radiological investigations, cystic fibrosis screening and the status of the contralateral vas deferens. Results All three patients were found to have congenital bilateral absence of the vas deferens, unilateral renal agenesis and were not found to have cystic fibrosis. Conclusions The combination of congenital bilateral absence of the vas deferens and unilateral renal agenesis, without cystic fibrosis, is rare and not reported previously in the paediatric literature. These findings require appropriate counselling of the parents and child, with regards to the long-term implications of infertility and renal function.
V. A. Lane (&) S. Scammell N. West G. V. Murthi Sheffield Children’s Hospital, Sheffield, UK e-mail: [email protected]
Keywords Absent vas deferens Renal agenesis Congenital
Introduction Groin surgery is commonly undertaken in male paediatric patients for the correction of inguinal hernia, hydrocele or the undescended testis. Occasionally, absence of the vas deferens will be demonstrated and many paediatric surgeons will simply perform a renal ultrasound to look for ipsilateral renal agenesis. We feel that it is also important to establish the status of the contralateral vas deferens (by concomitant laparoscopic evaluation or contralateral groin exploration) in addition to looking for abnormal renal anatomy. The finding of congenital bilateral absence of vas deferens (CBAVD) will automatically lead to the child being screened for cystic fibrosis (CF). On rare occasions, however, these investigations will reveal the unusual combination of CBAVD and unilateral renal agenesis (URA). Here, we report three patients diagnosed with CBAVD and URA and discuss the possible embryological basis for the uncommon entity, the clinical management pathway and the long-term implications of these findings.
Cases Case I An 18-month-old boy, previously known to have a solitary left kidney, was referred with an undescended left testis. He underwent a left orchidopexy at the age of 2 years, when an absent left vas deferens was noted. At routine outpatient review 6 months later, the testis had re-
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ascended, and was palpable in the groin. At the time of repeat orchidopexy, laparoscopy confirmed the presence of bilateral absence of the vas deferens. A left orchidectomy was performed, and histology confirmed a normal testicle with rudimentary epididymis. Cystic fibrosis screening for the common Western Europe mutations and a subsequent sweat test were negative. Case II A 2-month-old male infant born at 34/40 with an antenatal history of maternal drug use and intrauterine growth restriction was diagnosed post natally to have a left inguinal hernia and was referred for surgical assessment. At laparoscopic hernia repair, he was found to have bilateral inguinal herniae and CBAVD. On renal USS, he was found to have left renal agenesis. CF screening was negative. Case III A 2 year old boy underwent surgery for an undescended right testis. At operation, he was found to have an absent right vas deferens. Laparoscopy was performed and confirmed CBAVD and renal USS showed right renal agenesis. CF screening was negative. These clinical findings and investigations are summarised in Table 1.
Discussion Embryology Development of the genital system is closely integrated with the developing renal system. Three systems develop from the intermediate mesoderm: (1) the cervical nephrotomes (which are non-functioning), (2) the mesonephros which functions briefly in fetal life and (3) the sacral metanephric system, which forms the definitive kidneys. Table 1 Patient summary
Patient 1.Term infant
2.34/40 gestation
3.Term infant
123
The mesonephros and the mesonephric ducts develop simultaneously, following involution of the initial cervical nephrotomes in the intermediate mesoderm. Early in the 4th week of gestation, the mesonephric tubules develop within the mesonephros (the lateral tip of each mesonephric tubule fuses with a mesonephric duct) forming an excretory unit, which functions from weeks 6–10 and then regresses. In the female, the mesonephric ducts also regress; however, in the male, the mesonephric ducts persist to form the genital duct system. The final renal system is dependent on the ingrowth of the branching ureteric buds into the metanephric blastema, giving rise to the characteristic lobulated appearance we recognise as the definitive kidney. Each mesonephric duct, in the male, has two derivatives: (1) the ipsilateral ureteral/renal system and (2) the ipsilateral vas deferens, seminal vesicle and distal two-thirds of the epididymis. The physical separation of these two limbs occurs at about 7 weeks of gestation [1]. If an insult, whether genetic or toxic in nature, occurs prior to week 7, the entire mesonephric duct and its derivatives will be adversely affected. If the insult occurs after this time period, only one of the two bi-products may be affected. It is thus postulated that in patients with CBAVD/URA, the insult has occurred after 7 weeks of gestation, leading to absence of the vas deferens and the ipsilateral renal unit with preservation of the contralateral renal unit. The reason for the insult affecting both derivatives on one side and only the vas deferens on the contralateral side, leading to CBAVD/URA, remains elusive. Since males afflicted with clinical CF and bilateral absence of the vas deferens have normal renal anatomy, CFTR mutations probably do not affect the primitive mesonephric duct, and may exert their effect only on the developing reproductive ductal derivatives including the vas deferens, seminal vesicle and distal epididymis [2]. One theory postulates that atrophy and involution of the vas deferens and epididymal structures is caused by progressive obstruction of the genital duct by mucus and secretory protein accumulation, as a similar process to this
Presentation and findings
Renal USS
CF screening
Sweat test
Normal CFTR screen for the common Western Europe mutations
Negative
Normal CFTR screen for the common Western Europe mutations
Negative
Normal CFTR screen for the common Western Europe mutations
Negative
Left
Right
Undescended testis
Renal agenesis
Left
Left
Inguinal hernia
Renal agenesis
Right
Right
Undescended testis
Renal agenesis
Pediatr Surg Int (2014) 30:733–736
735 17/26 (65%) High sweat chloride
37 (79%) with normal renal anatomy 18/37 (49%) CFTR mutation identified
47 patients with CBAVD 10(21%) with renal malformations
10/10 (100%) No CFTR mutation identified, Sweat chloride normal
Fig. 1 Schematic representation of findings upon investigation of 47 patients with CBAVD by Augarten et al. [3]
is seen in the pancreas in those with CF [2]. Gaillard et al. [2] studied the aborted fetuses at 12 and 18 weeks of gestation, in those with an antenatal diagnosis of CF. No abnormality was seen in the vas deferens, suggesting a later insult, supporting this theory. However, patients with CBAVD (without CF) do not have altered secretions contradicting this theory and hence, the cause of the CBAVD remains unclear. In this regard, it is possible that men with CBAVD/ URA have a different genetic basis for their renal and vasal agenesis, to men with CBAVD/CF with normal renal anatomy. The presumed genetic anomaly would disrupt precise morphogenesis of the early mesonephric ducts. The most severe phenotypic manifestation would be bilateral renal agenesis, whereas men with CBAVD/ URA obviously possess a less severe phenotype. The transmission pattern has obviously been difficult to establish, as these men are infertile. However, with the advent of assisted reproduction techniques this is now potentially possible.
Relation of CBAVD/URA to CF Congenital bilateral absence of the vas deferens (CBAVD) in isolation is associated, most commonly, with cystic fibrosis (CF) and is recognised to occur in 98 % of males with the disease and the associated infertility is well recognised. Also, it is generally presumed that CBAVD patients with abnormal renal anatomy do not have CFTR gene mutations. In 1994, Augarten et al. [3] identified 47 adult patients with CBAVD and the results of subsequent investigations are summarised below in Fig. 1. None of the 10 patients with renal malformations had cystic fibrosis mutations, and sweat chloride concentrations were normal, leading them to suggest that CBAVD patients with renal malformations do not necessarily have cystic fibrosis. This was supported by subsequent studies [4, 5]. Robson et al. [6] stated that 70 % of boys with URA will have congenital unilateral absence of the vas (CUAVD), epididymis or seminal vesicle (CUAVD/URA), but the finding of CBAVD/URA is more unusual. CFTR mutations are generally not seen in this subset, and the pathophysiology of boys with these combined abnormalities may not be part of the CF mutation spectrum but may represent a different, discrete clinical and genetic entity. Whilst the various embryological and genetic hypotheses suggest that CBAVD/URA has a different aetiological basis to CBAVD associated with CF, of interest is the report by Daudin et al. [7]. They have reported four adult patients with the combination of CBAVD/URA. Two of these patients in fact carried a CFTR gene mutation (DF508/5T–9T and R117G/7T–9T) and the other two patients were free of CFTR mutations and the 5T allele. This finding shows that our understanding of the aetiology of this condition is far from complete. On a clinical level, it indicates the need to perform genetic testing in all patients with CBAVD/URA as some may have associated CF-related genetic abnormalities with implications for
Fig. 2 Recommended pathway upon finding absent vas at groin exploration
Absent vas at groin exploration
Concomitant laparoscopic visualisation for status of opposite vas + Renal ultrasound scan
Bilateral absence of vas
Unilateral absence of vas
Normal kidneys or Unilateral renal agenesis
Test for CF irrespective of renal status
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736
counselling and further management not only of their expected infertility, but also of the CF-related genetic abnormalities. Previously, the inheritance pattern of CBAVD was difficult to ascertain due to the functional infertility. However, with the increased use of assisted conception, this is now potentially possible. McCallum et al. [8] looked at the rates of URA in the CBAVD population presenting with infertility. They identified 168 men with CBAVD. The majority of their patients 97 (58 %) had CBAVD, normal renal anatomy and an identifiable CFTR mutation. 17/168 (10 %) had CBAVD/URA and no CFTR mutations. Two men were found to have a pelvic kidney. The remaining 54 were excluded from the study because of inadequate data. Of potential interest in this study, were the 17 men with CBAVD/URA, as 12 opted for assisted conception enabling possible inheritance patterns to be ascertained. Family members were screened for abnormal renal anatomy (15 parents, 15 siblings, 10 conceptions and 3 nieces/ nephews). One fetus was found to have bilateral renal agenesis and the pregnancy was terminated. At post mortem, the fetus was found to have complete renal agenesis, absent ureters and absent vas deferens bilaterally. All other relatives were normal, unfortunately drawing little conclusion. Patient management algorithm When absence of vas deferens is identified at groin exploration, we recommend the following sequence of investigations as shown in Fig. 2. Counselling issues in the paediatric population Parents of patients with CBAVD/URA need counselling for the long-term implications of infertility and a single kidney. In our institution, they are counselled for these issues by our Cystic Fibrosis team and the nephrologist, respectively.
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Conclusion In conclusion, the exact pathophysiology of CBAVD remains poorly understood. The findings of an absent vas deferens, at the time of groin surgery, should prompt the surgeon to: (1) explore the status of the contralateral vas deferens, preferably by laparoscopy under the same general anaesthetic, and (2) conduct a renal tract ultrasound scan. The finding of CBAVD should prompt tests for CF, irrespective of the status of the kidneys. Where the rare combination of CBAVD/URA is discovered appropriate counselling should be arranged.
References 1. Gibbons MD, Chromic WJ, Duckett JW (1978) Ectopic vas deferens. J Urol 120:597–604 2. Gaillard DA, Carre-Pigeon F, Lallemand A (1997) Normal vas deferens in fetuses with cystic fibrosis. J Urol 158:1549–1552 3. Augarten A, Yahav Y, Kerem Bs et al (1994) Congenital bilateral absence of the vas deferens in the absence of cystic fibrosis. Lancet 344:1473–1474 4. Dork T, Dworniczak B, Aulehla-Scholz C et al (1997) Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens. Human Genet 100:371–374 5. Schwarzer JU, Schwarz M (2012) Significance of CFTR gene mutations in patients with congenital aplasia of vas deferens with special regard to renal aplasia. Andrologia 44:305–307 6. Robson WL, Leung AK, Rodgers RC (1995) Unilateral renal agenesis. Adv Pediatr 42:575–592 7. Daudin M, Bieth E, Bujan L, Massat G, Pontonnier F, Mieusset R (2000) Congenital bilateral absence of the vas deferens: clinical characteristics, biological parameters, cystic fibrosis transmembrane conductance regulator gene mutations, and implications for genetic counseling. Fertil Steril 74(6):1164–1174 8. McCallum TJ, Milunsky JM, Munarriz R et al (2001) Unilateral renal agenesis associated with congenital bilateral absence of the vas deferens: phenotypic findings and genetic considerations. Hum Reprod 16(2):282–288
ORIGINAL ARTICLE
Congenital absence of the vas deferens and unilateral renal agenesis: implications for patient and family Victoria Alison Lane • Simon Scammell Noreen West • Govind V. Murthi
•
Accepted: 22 May 2014 / Published online: 31 May 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Background and aims At routine groin surgery in male paediatric patients occasionally the vas deferens may be absent. This finding usually leads to investigations to establish the status of the contralateral vas deferens and the status of the kidneys. It is not uncommon to find either an ipsilateral renal agenesis or congenital bilateral absence of the vas deferens. The latter finding prompts a test for cystic fibrosis. We report three patients who upon investigation were found to have the rare combination of congenital bilateral absence of the vas deferens and unilateral renal agenesis, and discuss the possible embryological basis, the clinical management and the long-term implications of these findings. Patients and methods We present three patients who were incidentally found to have absence of the vas deferens whilst undergoing elective groin surgery and following further tests were diagnosed with congenital bilateral absence of the vas deferens and unilateral renal agenesis. The case notes were reviewed, together with the results of radiological investigations, cystic fibrosis screening and the status of the contralateral vas deferens. Results All three patients were found to have congenital bilateral absence of the vas deferens, unilateral renal agenesis and were not found to have cystic fibrosis. Conclusions The combination of congenital bilateral absence of the vas deferens and unilateral renal agenesis, without cystic fibrosis, is rare and not reported previously in the paediatric literature. These findings require appropriate counselling of the parents and child, with regards to the long-term implications of infertility and renal function.
V. A. Lane (&) S. Scammell N. West G. V. Murthi Sheffield Children’s Hospital, Sheffield, UK e-mail: [email protected]
Keywords Absent vas deferens Renal agenesis Congenital
Introduction Groin surgery is commonly undertaken in male paediatric patients for the correction of inguinal hernia, hydrocele or the undescended testis. Occasionally, absence of the vas deferens will be demonstrated and many paediatric surgeons will simply perform a renal ultrasound to look for ipsilateral renal agenesis. We feel that it is also important to establish the status of the contralateral vas deferens (by concomitant laparoscopic evaluation or contralateral groin exploration) in addition to looking for abnormal renal anatomy. The finding of congenital bilateral absence of vas deferens (CBAVD) will automatically lead to the child being screened for cystic fibrosis (CF). On rare occasions, however, these investigations will reveal the unusual combination of CBAVD and unilateral renal agenesis (URA). Here, we report three patients diagnosed with CBAVD and URA and discuss the possible embryological basis for the uncommon entity, the clinical management pathway and the long-term implications of these findings.
Cases Case I An 18-month-old boy, previously known to have a solitary left kidney, was referred with an undescended left testis. He underwent a left orchidopexy at the age of 2 years, when an absent left vas deferens was noted. At routine outpatient review 6 months later, the testis had re-
123
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Pediatr Surg Int (2014) 30:733–736
ascended, and was palpable in the groin. At the time of repeat orchidopexy, laparoscopy confirmed the presence of bilateral absence of the vas deferens. A left orchidectomy was performed, and histology confirmed a normal testicle with rudimentary epididymis. Cystic fibrosis screening for the common Western Europe mutations and a subsequent sweat test were negative. Case II A 2-month-old male infant born at 34/40 with an antenatal history of maternal drug use and intrauterine growth restriction was diagnosed post natally to have a left inguinal hernia and was referred for surgical assessment. At laparoscopic hernia repair, he was found to have bilateral inguinal herniae and CBAVD. On renal USS, he was found to have left renal agenesis. CF screening was negative. Case III A 2 year old boy underwent surgery for an undescended right testis. At operation, he was found to have an absent right vas deferens. Laparoscopy was performed and confirmed CBAVD and renal USS showed right renal agenesis. CF screening was negative. These clinical findings and investigations are summarised in Table 1.
Discussion Embryology Development of the genital system is closely integrated with the developing renal system. Three systems develop from the intermediate mesoderm: (1) the cervical nephrotomes (which are non-functioning), (2) the mesonephros which functions briefly in fetal life and (3) the sacral metanephric system, which forms the definitive kidneys. Table 1 Patient summary
Patient 1.Term infant
2.34/40 gestation
3.Term infant
123
The mesonephros and the mesonephric ducts develop simultaneously, following involution of the initial cervical nephrotomes in the intermediate mesoderm. Early in the 4th week of gestation, the mesonephric tubules develop within the mesonephros (the lateral tip of each mesonephric tubule fuses with a mesonephric duct) forming an excretory unit, which functions from weeks 6–10 and then regresses. In the female, the mesonephric ducts also regress; however, in the male, the mesonephric ducts persist to form the genital duct system. The final renal system is dependent on the ingrowth of the branching ureteric buds into the metanephric blastema, giving rise to the characteristic lobulated appearance we recognise as the definitive kidney. Each mesonephric duct, in the male, has two derivatives: (1) the ipsilateral ureteral/renal system and (2) the ipsilateral vas deferens, seminal vesicle and distal two-thirds of the epididymis. The physical separation of these two limbs occurs at about 7 weeks of gestation [1]. If an insult, whether genetic or toxic in nature, occurs prior to week 7, the entire mesonephric duct and its derivatives will be adversely affected. If the insult occurs after this time period, only one of the two bi-products may be affected. It is thus postulated that in patients with CBAVD/URA, the insult has occurred after 7 weeks of gestation, leading to absence of the vas deferens and the ipsilateral renal unit with preservation of the contralateral renal unit. The reason for the insult affecting both derivatives on one side and only the vas deferens on the contralateral side, leading to CBAVD/URA, remains elusive. Since males afflicted with clinical CF and bilateral absence of the vas deferens have normal renal anatomy, CFTR mutations probably do not affect the primitive mesonephric duct, and may exert their effect only on the developing reproductive ductal derivatives including the vas deferens, seminal vesicle and distal epididymis [2]. One theory postulates that atrophy and involution of the vas deferens and epididymal structures is caused by progressive obstruction of the genital duct by mucus and secretory protein accumulation, as a similar process to this
Presentation and findings
Renal USS
CF screening
Sweat test
Normal CFTR screen for the common Western Europe mutations
Negative
Normal CFTR screen for the common Western Europe mutations
Negative
Normal CFTR screen for the common Western Europe mutations
Negative
Left
Right
Undescended testis
Renal agenesis
Left
Left
Inguinal hernia
Renal agenesis
Right
Right
Undescended testis
Renal agenesis
Pediatr Surg Int (2014) 30:733–736
735 17/26 (65%) High sweat chloride
37 (79%) with normal renal anatomy 18/37 (49%) CFTR mutation identified
47 patients with CBAVD 10(21%) with renal malformations
10/10 (100%) No CFTR mutation identified, Sweat chloride normal
Fig. 1 Schematic representation of findings upon investigation of 47 patients with CBAVD by Augarten et al. [3]
is seen in the pancreas in those with CF [2]. Gaillard et al. [2] studied the aborted fetuses at 12 and 18 weeks of gestation, in those with an antenatal diagnosis of CF. No abnormality was seen in the vas deferens, suggesting a later insult, supporting this theory. However, patients with CBAVD (without CF) do not have altered secretions contradicting this theory and hence, the cause of the CBAVD remains unclear. In this regard, it is possible that men with CBAVD/ URA have a different genetic basis for their renal and vasal agenesis, to men with CBAVD/CF with normal renal anatomy. The presumed genetic anomaly would disrupt precise morphogenesis of the early mesonephric ducts. The most severe phenotypic manifestation would be bilateral renal agenesis, whereas men with CBAVD/ URA obviously possess a less severe phenotype. The transmission pattern has obviously been difficult to establish, as these men are infertile. However, with the advent of assisted reproduction techniques this is now potentially possible.
Relation of CBAVD/URA to CF Congenital bilateral absence of the vas deferens (CBAVD) in isolation is associated, most commonly, with cystic fibrosis (CF) and is recognised to occur in 98 % of males with the disease and the associated infertility is well recognised. Also, it is generally presumed that CBAVD patients with abnormal renal anatomy do not have CFTR gene mutations. In 1994, Augarten et al. [3] identified 47 adult patients with CBAVD and the results of subsequent investigations are summarised below in Fig. 1. None of the 10 patients with renal malformations had cystic fibrosis mutations, and sweat chloride concentrations were normal, leading them to suggest that CBAVD patients with renal malformations do not necessarily have cystic fibrosis. This was supported by subsequent studies [4, 5]. Robson et al. [6] stated that 70 % of boys with URA will have congenital unilateral absence of the vas (CUAVD), epididymis or seminal vesicle (CUAVD/URA), but the finding of CBAVD/URA is more unusual. CFTR mutations are generally not seen in this subset, and the pathophysiology of boys with these combined abnormalities may not be part of the CF mutation spectrum but may represent a different, discrete clinical and genetic entity. Whilst the various embryological and genetic hypotheses suggest that CBAVD/URA has a different aetiological basis to CBAVD associated with CF, of interest is the report by Daudin et al. [7]. They have reported four adult patients with the combination of CBAVD/URA. Two of these patients in fact carried a CFTR gene mutation (DF508/5T–9T and R117G/7T–9T) and the other two patients were free of CFTR mutations and the 5T allele. This finding shows that our understanding of the aetiology of this condition is far from complete. On a clinical level, it indicates the need to perform genetic testing in all patients with CBAVD/URA as some may have associated CF-related genetic abnormalities with implications for
Fig. 2 Recommended pathway upon finding absent vas at groin exploration
Absent vas at groin exploration
Concomitant laparoscopic visualisation for status of opposite vas + Renal ultrasound scan
Bilateral absence of vas
Unilateral absence of vas
Normal kidneys or Unilateral renal agenesis
Test for CF irrespective of renal status
123
736
counselling and further management not only of their expected infertility, but also of the CF-related genetic abnormalities. Previously, the inheritance pattern of CBAVD was difficult to ascertain due to the functional infertility. However, with the increased use of assisted conception, this is now potentially possible. McCallum et al. [8] looked at the rates of URA in the CBAVD population presenting with infertility. They identified 168 men with CBAVD. The majority of their patients 97 (58 %) had CBAVD, normal renal anatomy and an identifiable CFTR mutation. 17/168 (10 %) had CBAVD/URA and no CFTR mutations. Two men were found to have a pelvic kidney. The remaining 54 were excluded from the study because of inadequate data. Of potential interest in this study, were the 17 men with CBAVD/URA, as 12 opted for assisted conception enabling possible inheritance patterns to be ascertained. Family members were screened for abnormal renal anatomy (15 parents, 15 siblings, 10 conceptions and 3 nieces/ nephews). One fetus was found to have bilateral renal agenesis and the pregnancy was terminated. At post mortem, the fetus was found to have complete renal agenesis, absent ureters and absent vas deferens bilaterally. All other relatives were normal, unfortunately drawing little conclusion. Patient management algorithm When absence of vas deferens is identified at groin exploration, we recommend the following sequence of investigations as shown in Fig. 2. Counselling issues in the paediatric population Parents of patients with CBAVD/URA need counselling for the long-term implications of infertility and a single kidney. In our institution, they are counselled for these issues by our Cystic Fibrosis team and the nephrologist, respectively.
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Pediatr Surg Int (2014) 30:733–736
Conclusion In conclusion, the exact pathophysiology of CBAVD remains poorly understood. The findings of an absent vas deferens, at the time of groin surgery, should prompt the surgeon to: (1) explore the status of the contralateral vas deferens, preferably by laparoscopy under the same general anaesthetic, and (2) conduct a renal tract ultrasound scan. The finding of CBAVD should prompt tests for CF, irrespective of the status of the kidneys. Where the rare combination of CBAVD/URA is discovered appropriate counselling should be arranged.
References 1. Gibbons MD, Chromic WJ, Duckett JW (1978) Ectopic vas deferens. J Urol 120:597–604 2. Gaillard DA, Carre-Pigeon F, Lallemand A (1997) Normal vas deferens in fetuses with cystic fibrosis. J Urol 158:1549–1552 3. Augarten A, Yahav Y, Kerem Bs et al (1994) Congenital bilateral absence of the vas deferens in the absence of cystic fibrosis. Lancet 344:1473–1474 4. Dork T, Dworniczak B, Aulehla-Scholz C et al (1997) Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens. Human Genet 100:371–374 5. Schwarzer JU, Schwarz M (2012) Significance of CFTR gene mutations in patients with congenital aplasia of vas deferens with special regard to renal aplasia. Andrologia 44:305–307 6. Robson WL, Leung AK, Rodgers RC (1995) Unilateral renal agenesis. Adv Pediatr 42:575–592 7. Daudin M, Bieth E, Bujan L, Massat G, Pontonnier F, Mieusset R (2000) Congenital bilateral absence of the vas deferens: clinical characteristics, biological parameters, cystic fibrosis transmembrane conductance regulator gene mutations, and implications for genetic counseling. Fertil Steril 74(6):1164–1174 8. McCallum TJ, Milunsky JM, Munarriz R et al (2001) Unilateral renal agenesis associated with congenital bilateral absence of the vas deferens: phenotypic findings and genetic considerations. Hum Reprod 16(2):282–288
