Is bilateral congenital anorchia genetically determined?

Bilateral congenital anorchia (BCA) can be defined as complete absence of testicular tissue in a patient with male normal phenotype and karyotype. On the basis of familial occurrences of BCA a possible genetic aetiology has been hypothesised, i.e. mutations of the SRY gene which initiates the genetic cascade leading to testis development in mammals. The aim of the study is to assess this hypothesis. Eight boys affected by BCA have been studied; a normal monozygotic twin of one of the patients, a boy and a girl acted as controls. A normal 46, XY karyotype was detected in all patients; 3 had hypoplasia of the scrotum and 2 of the penis. Hormonal data were available for 5 patients: Prader's stimulation test to HCG showed in all lack of testosterone response, and 4 out of 5 had elevated FSH and LH levels. Complete absence of testicular tissue was confirmed in all by surgical exploration. DNA was sampled by Jeanpierre modified extraction method and amplification by polymerase chain reaction. The expected segment of 750 basepairs of the SRY gene, included between the two oligonucleotide primers Xes 10 and Xes 11, was found in all patients. SRY gene is present in our BCA patients as well as in normal boys, and therefore BCA does not seem related to an anomaly of the opening reading frame sequence of the SRY gene. Nevertheless, familial occurrences of BCA continue to suggest a genetic aetiology: further studies must therefore evaluate the possibility of punctiform mutations of the SRY gene, by direct sequentiation, and exclude abnormalities in the critical region DSS/AHC of the X chromosome, recently discovered as one of the loci involved in the differentiation of the male gonad.