Is bilateral congenital anorchia genetically determined?

Bilateral congenital anorchia (BCA) can be defined as complete absence of t esticular tissue in a patient with male normal phenotype and karyotype. On the basis of familial occurrences of BCA a possible genetic aetiology has b een hypothesised, i.e. mutations of the SRY gene which initiates the geneti c 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 ka ryotype 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 stimul ation 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 wa s confirmed in all by surgical exploration. DNA was sampled by jeanpierre m odified extraction method and amplification by polymerase chain reaction. T he expected segment of 750 basepairs of the SRY gene, included between the two oligonucleotide primers Xes 10 and Xes 11, was found in ail patients. SRY gene is present in our BCA patients as well as in normal boys, and ther efore BCA does not seem related to an anomaly of the opening reading frame sequence of the SRY gene, Nevertheless, familial occurrences of BCA continu e to suggest a genetic aetiology: further studies must therefore evaluate t he possibility of punctiform mutations of the SRY gene, by direct sequentia tion, and exclude abnormalities in the critical region DSS/AHC of the X chr omosome, recently discovered as one of the loci involved in the differentia tion of the male gonad.