Characterizing the Clinical and Genetic Spectrum of Bilateral Vasal Agenesis in a Cohort of 168 Men

Abstract

Objective: A link between bilateral vasal agenesis and mutations in the cystic fibrosis (CF) genes is well established, but not all men have a gene anomaly. At one end of the phenotypic continuum is clinical CF while at the other is Congenital Bilateral Absence of the Vas Deferens (CBAVD) and no detectable mutation. A small percentage have unilateral renal agenesis (URA). The purpose of this study is to further enhance and define the phenotypic, radiologic, and genetic spectrum of the bilateral vasal agenesis syndromes.Design: Retrospective review of 168 men with bilateral vasal agenesis (1988 to 1999). Groups defined as: 1. clinical CF (CF), 2. CBAVD with CF gene mutations (CBAVD/CF), 3. CBAVD with URA (CBAVD/URA), 4. CBAVD—no CF mutations (CBAVD/--).Materials and Methods: History, physical exam, semen analysis, transrectal ultrasound (TRUS), and CFTR mutation, (up to 26 mutations, poly T tract assayed since 1997) were completed and the results for each group tabulated and subjected to Chi Square statistical analysis (Excel software package).Results: Classification: CF: 12; CBAVD/CF: 85; CBAVD/URA: 17; CBAVD/--: 54. There was no statistical difference seen between the 4 groups with regards to semen analysis volume or pH length of the epididymal remnant or the presence or absence of seminal vesicles as determined by TRUS. Clinical CF was associated with a compound state more often than CBAVD/CF (p<.01).Table 1. Tabled 1CFCBAVD/CFCBAVD/URACBAVD/--Epididymides:Caput only22 (92%)120 (76%)28 (82%)61 (65%)Additional remnant present2 (8%)38 (24%)6 (18%)33 (35%)Seminal Vesicles:Agenesis10 (50%)52 (42%)20 (62%)44 (54%)Additional remnant present72 (58%12 (38%)38 (46%)CFTR Status:Compound heterozygote9 (75%)6 (7%)00Simple heterozygote1 (8%)79 (94%)2 (13%)0With 5T variant12500Without 5T variant03220 Open table in a new tab Conclusions: There are at least 4 subtypes of bilateral vasal agenesis. CF and CBAVD/CF are genetic related but phenotypically different in terms of pulmonary and pancreatic disease. CBAVD/URA may have a completely different genetic etiology not secondary to anomalies of the CF genes. CBAVD/-- is of unclear etiology and may or may not be related to the either of the previous two groups. However, all appear to have the same ultimate phenotypic expression regarding the vasa, epididymides and seminal vesicles. Objective: A link between bilateral vasal agenesis and mutations in the cystic fibrosis (CF) genes is well established, but not all men have a gene anomaly. At one end of the phenotypic continuum is clinical CF while at the other is Congenital Bilateral Absence of the Vas Deferens (CBAVD) and no detectable mutation. A small percentage have unilateral renal agenesis (URA). The purpose of this study is to further enhance and define the phenotypic, radiologic, and genetic spectrum of the bilateral vasal agenesis syndromes. Design: Retrospective review of 168 men with bilateral vasal agenesis (1988 to 1999). Groups defined as: 1. clinical CF (CF), 2. CBAVD with CF gene mutations (CBAVD/CF), 3. CBAVD with URA (CBAVD/URA), 4. CBAVD—no CF mutations (CBAVD/--). Materials and Methods: History, physical exam, semen analysis, transrectal ultrasound (TRUS), and CFTR mutation, (up to 26 mutations, poly T tract assayed since 1997) were completed and the results for each group tabulated and subjected to Chi Square statistical analysis (Excel software package). Results: Classification: CF: 12; CBAVD/CF: 85; CBAVD/URA: 17; CBAVD/--: 54. There was no statistical difference seen between the 4 groups with regards to semen analysis volume or pH length of the epididymal remnant or the presence or absence of seminal vesicles as determined by TRUS. Clinical CF was associated with a compound state more often than CBAVD/CF (p<.01). Table 1. Tabled 1CFCBAVD/CFCBAVD/URACBAVD/--Epididymides:Caput only22 (92%)120 (76%)28 (82%)61 (65%)Additional remnant present2 (8%)38 (24%)6 (18%)33 (35%)Seminal Vesicles:Agenesis10 (50%)52 (42%)20 (62%)44 (54%)Additional remnant present72 (58%12 (38%)38 (46%)CFTR Status:Compound heterozygote9 (75%)6 (7%)00Simple heterozygote1 (8%)79 (94%)2 (13%)0With 5T variant12500Without 5T variant03220 Open table in a new tab Conclusions: There are at least 4 subtypes of bilateral vasal agenesis. CF and CBAVD/CF are genetic related but phenotypically different in terms of pulmonary and pancreatic disease. CBAVD/URA may have a completely different genetic etiology not secondary to anomalies of the CF genes. CBAVD/-- is of unclear etiology and may or may not be related to the either of the previous two groups. However, all appear to have the same ultimate phenotypic expression regarding the vasa, epididymides and seminal vesicles.