Clinical and Endocrinological Characterization of Two Subjects with Reifenstein Syndrome Associated with Qualitative Abnormalities of the Androgen Receptor

Abstract

The androgen receptor in fibroblasts cultured from a biopsy of scrotal skin from 1 subject with Reifenstein syndrome has been found to be normal in amount and to bind dihydrotestosterone with normal affinity but to be qualitatively abnormal as evident by thermolability and instability upon ultracentrifugation. The family study of this subject and endocrine studies document androgen resistance in the index patient and his affected uncle. These findings provide evidence for X-linkage of this disorder, and suggest that the mutations that give rise to this phenotype are probably allelic to the mutations of the androgen receptor that cause testicular feminization.

Incomplete Androgen Insensitivity Associated with a Thermolabile Androgen Receptor.

“…The presence of thermolabile androgen receptor (qualitatively abnormal androgen receptor) made the diagnosis convincing. Thermolabile androgen receptors have been observed in complete AIS [4,5], incomplete AIS [6], the Reifeinstein syndrome [7] and the infertile male syndrome [8], indicating that patients with thermolabile androgen receptors span a wide spectrum. Further study is required to elucidate these forms of phenotypic heterogeniety in patients with thermolabile androgen receptors.…”

Androgen receptor disorder in three brothers with bifid prepenile scrotum and hypospadias

“…Male pseudohermaphroditism characterized by infertility, ambiguous genitalia, gynecomastia and elevated testosterone, estradiol and LH values is known as the Reifenstein syndrome (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). It is a syndrome with variable mutations of the gene, which is possibly transmitted by the X-chromosome (14). Linkage studies with genes known to be Xlinked, such as colour blindness and blood group antigen Xga, provide one possible resolution of this question.…”

Testosterone

“…A similar array of androgen receptor defects as described above for patients with testicular feminization is found, namely, quantitatively and qualitatively abnormal high affinity dihydrotestosterone binding as well as receptor positive patients with no apparent abnormality in receptor function (Wilson et al 1974;Griffin et al 1976;Amrhein et al 1977;Griffin 1979;Griffin and Durrant 1982;Kaufman et al 1984;Schweikert et al 1987b). A similar array of androgen receptor defects as described above for patients with testicular feminization is found, namely, quantitatively and qualitatively abnormal high affinity dihydrotestosterone binding as well as receptor positive patients with no apparent abnormality in receptor function (Wilson et al 1974;Griffin et al 1976;Amrhein et al 1977;Griffin 1979;Griffin and Durrant 1982;Kaufman et al 1984;Schweikert et al 1987b).…”

“…The mode of inheritance of these syndromes is most probably X -linked recessive, however, sporadic cases are common (Amrhein et al 1977;Schweikert et al 1987b). …”

“…Testicular estrogen secretion is also increased (Wilson et al 1974;Amrhein et al 1977;Boyar et al 1978;Schweikert et al 1987b). Testicular estrogen secretion is also increased (Wilson et al 1974;Amrhein et al 1977;Boyar et al 1978;Schweikert et al 1987b).…”