The clinical and molecular spectrum of androgen insensitivity syndromes

Androgen insensitivity syndromes (AIS) are due to end-organ resistance to androgenic steroids in males leading to defective virilization of the external genitalia. The phenotype encompasses a wide array of genital ambiguity and may range from completely female to undervirilized but unequivocally male with infertility. This disorder is caused by mutations of the androgen receptor and is an X-linked recessive trait. We have studied 47 patients with AIS and have characterized the underlying molecular abnormality in the androgen receptor gene. Twenty patients had complete AIS and twenty-seven had partial AIS. Of the latter, 11 were of predominantly female phenotypic appearance and gender was assigned accordingly, while 16 were raised as males. Within the group of complete AIS, two patients had gross deletions within the gene, one had a small deletion, and one had an insertion. In the other patients with complete AIS, as well as all individuals with partial AIS, single nucleotide substitutions within the coding region were detected, each leading to an amino acid alteration. Seven codons were involved in more than one mutation in different cases. In addition, in one patient with spinal and bulbar muscular atrophy, an elongation of a glutamine-repeat was characterized. We conclude that mutations in the androgen receptor gene may be present throughout the whole coding region. However, our study provides evidence that several mutational hot spots exist. © 1996 Wiley-Liss, Inc.     

Persistent Müllerian Duct Syndrome Associated with Irreducible Inguinal Hernia,Bilateral Cryptorchidism and Testicular Neoplasia: a Case Report

Persistent müllerian duct syndrome is a rare form of male pseudohermaphroditism. A case is reported of normal male appearance with bilateral cryptorchidism and a right irreducible inguinal hernia. On exploration, an uterus with two fallopian tubes and a testicle were found in the hernia sac. The uterus, fallopian tubes and left testicle were en bloc removed. Right orchidopexy and hernia repair were performed.

In conclusion, if there is an adult bilateral cryptorchidism, surgeons should take into consideration a persistent müller-ian duct syndrome.     

Molecular and clinical studies of three cases of female pseudohermaphroditism with caudal dysplasia suggest multiple etiologies

Female pseudohermaphroditism with caudal dysplasia is a clinical entity in which normal-appearing male genitalia may occur in the apparent absence of testosterone or the sex-determining gene ( SRY ). We have extended observations of two previously reported cases, and report a third case, which strongly suggests multiple etiologies. The first case was one of identical twins. The other identical twin did not show female pseudohermaphroditism with caudal dysplasia, but both patients had the rare birth defect of neonatal cataracts. We have explored skewed X-inactivation as a possible difference between the two twins, with a negative result. The second case had a deletion at 10q25.3→ter. This is near the location of PAX 2, and we searched for mutations in PAX 2 in both this and the first case, with negative results. Neither patient had a scrotal raphe, suggesting that a failure of division of the cloacal membrane was an important step in their development of female pseudohermaphroditism. The final case is newly described and differed from the above two in the presence of a scrotal raphe and an elevated testosterone level. Although no source for the testosterone was found, this case suggests that the etiology in this patient was different and that the presence of a scrotal raphe can be used to distinguish between at least two etiologies.     

CORRELATIONS BETWEEN FIBROBLAST ANDROGEN RECEPTOR LEVELS and CLINICAL FEATURES IN ABNORMAL MALE SEXUAL DIFFERENTIATION and INFERTILITY

Androgen receptor binding of radiolabelled methyltrienolone (³H-R1881) was determined in cultured genital skin fibroblasts from 17 normal male controls and from 65 males with genital abnormalities. Analysis of the results was performed with patients grouped according to the predominant clinical features. Of 16 patients with complete male pseudohermaphroditism, 12 had androgen receptor (AR) deficiency, one had “receptor-positive” Testicular Feminization, and in three, alternative diagnoses were established (17ahydroxylase deficiency; 20,22-desmolase deficiency; mixed gonadal dysgenesis). In contrast, only four of 16 patients investigated for ambiguous genitalia (phallus intermediate between male and female, perineal urethra) showed AR deficiency. Borderline or slightly low AR levels were found in each of four boys in whom the sole abnormality was micropenis. In 26 boys with penile hypospadias, however, only one had low AR. Very low levels of AR (levels comparable to those seen in complete Testicular Feminization) were found in two of three men with infertility associated with abnormally high serum testosterone levels.     

Imaging presentation of adrenal glands in female pseudohermaphroditism

Objective： To discuss imaging features of the adrenal glands in female pseudohermaphroditism. Methods： 11 cases of female pseudohermaphroditism （8-27 years old） were analyzed retrospectively. Results： In 9 of the 11 patients with female pseudohermaphroditism who did no receive hormone replacement therapy, both internal and external branches of bilateral adrenal glands were found to be thickened, prolonged and twisted, and in 2 of the 9 patients they were found to be macronodularly hyperplasic. In one of the remaining two patients who had received long-term hormone replacement therapy, the adrenal glands were not thickened or twisted, though prolonged; and in the other patient imaging presentation of the adrenal glands was the same as that of those who did not receive hormone replacement therapy, but with co-existence of adrenal myelolipoma. Among the 11 patients agenesis of the uterus and the vagina was found in 4 cases. Conclusion： Female pseudohermaphroditism is a hereditary disease, where hyperplasia of the adrenal glands and agenesis of the uterus and the vagina were secondary. Early detection of these abnormalities by imageology would prove to be helpful in early detection and treatment of the condition.     

先天性肾上腺皮质增生所致女性假两性畸形的CT 诊断及临床表现

目的：探讨先天性肾上腺皮质增生所致女性假两性畸形的CT 表现特点及诊断价值。方法经手术及临床诊断为先天性肾上腺皮质增生所致女性假两性畸形6例患者，分析其CT 表现及特点。结果6例患者均未经激素治疗，双侧肾上腺内外肢弥漫性增粗、迂曲、延长，1例表现为结节状、串珠状增生；轮廓清晰，密度均匀，增强扫描呈明显、均匀、同步强化。结论肾上腺弥漫性、串珠状增生有一定的特征性，有助于提高女性假两性畸形的影像诊断敏感性，结合临床综合分析，做出正确诊断。     

26例女性假两性畸形分析

女性假两性畸形26例,染色体均为46,xx。未成年者其社会性别女性11例,男性7例;成年者女性6例,男性2例。因生后阴蒂大而将其中9例作为男孩抚养。经查明,1例为母孕期服大量雄激素所致。5例开腹探查发现内生殖器均为子宫及卵巢,而地塞米松抑制试验亦为阳性,6例查尿17—酮均高于正常值。这种病人尽管外生殖器有不同程度男性化,而性腺及内生殖器均为女性。此类患者一旦确诊,不需要再行腹探查,早治疗可使患儿得到正常的生长发育。     

High frequency of congenital adrenal hyperplasia (classic 11β-hydroxylase deficiency) among Jews from Morocco

Steroid 11β-hydroxylase deficiency is relatively frequent in Israel among North African Jews. Over a 39-year period, 38 affected individuals from 25 families were diagnosed. Nineteen families came from Morocco, and in another 2, one parent came from Morocco (80% of all parents). Demographic studies showed that most of their grandparents were born in the region of the Atlas Mountains. In Israel, the overall incidence of the disorder is estimated between 1 in 30,000 to 1 40,000 births, but in offspring of Moroccan Jews the ratio is 1 in 5,000 to 1 in 7,000, with an allele frequency of 1 in 70 to 1 in 84 and a carrier frequency of 1 in 35 to 1 in 42. The clinical expression in characterized by a wide range of variability in the signs of androgen and mineralocorticoid excess. Virilization in the female ranged from enlarged clitoris in the mildest forms, to markedly hypertrophied clitoris with penile urethra and fused labial-scrotal folds in the most severe forms. Hypertension causing vascular accidents and death was observed in both severe and mildly virilized patients, whereas masculinized females were sometimes normotensive. Based on historical evidence, the origin of the ancestors, and the onomastic analysis of the families surnames, we propose that the mutation of 11β-hydroxylase dificiency in Jews from Morocco may have originated in either the ancient Jewish settlers or the native Berber tribes who lived in the region of the Atlas Mountains in the southern region of Morocco before the destruction of the Second Temple by the Romans, in the year 70 C.E.     

肾上腺皮质增生致女性假两性畸形手术治疗（附2例报告）

目的探讨保留血管神经蒂阴蒂成形术在手术治疗假两性畸形的应用。方法 2例女性假两性畸形,行保留血管神经蒂阴蒂成形术,切除肥大阴蒂体部,保留阴蒂背侧血管神经及腹侧包皮皮瓣形成小阴唇。术后糖皮质激素长期口服治疗。结果 2例术后切口均一期愈合,再造之阴蒂完全成活,感觉敏锐,外阴形态满意。结论保留血管神经蒂阴蒂成形术可在改善阴蒂外观的同时保留其感觉及勃起功能,恢复外阴外观,符合生理特征。