Ambiguous genitalia: an overview of 17 years' experience

Aim

The newborn with abnormal genital development presents a difficult diagnostic and treatment challenge for the pediatric surgeon providing care. The purpose of this study was to evaluate the results of surgical treatment for children with ambiguous genitalia.

Patients and Methods

The records of 85 children managed surgically for ambiguous genitalia in our unit from 1988 to 2005 were reviewed retrospectively. Age at surgery, operative procedures, sex of rearing, and outcome were recorded.

Results

The intersex committee's decision concerning sex assignment was female for 62 children (75%) and male for 23 children (25%). The etiologies of children reared as female were congenital adrenal hyperplasia (n = 37), male pseudohermaphroditism (n = 12), mixed gonadal dysgenesis (n = 6), true hermaphroditism (n = 4), and Mayer-Rokitansky syndrome (n = 3). Fifteen children with male pseudohermaphroditism, 5 children with congenital adrenal hyperplasia, and 3 children with true hermaphroditism were reared as male. The mean age at surgery was 4.4 years and follow-up period averaged 7 years. Eighteen (29%) patients with feminization procedures and 8 (34%) of 23 patients with masculinization procedures experienced complications and required redo operations. Vaginal stenosis was the most common complication.

Conclusion

The surgical management of ambiguous genitalia has always been difficult, and it must be performed by skilled pediatric surgeon. Genital surgery in infancy needs to be reassessed in the light of literature findings revealing poor outcome. In patients who underwent feminizing genitoplasty, vaginal reconstruction should be delayed until adolescence to achieve better cosmetic and functional results.     

女性假两性畸形的诊断和治疗

目的：探讨女性假两性畸形的临床诊断及治疗方法。方法：回顾性分析6例女性假两性畸形的临床资料：6例患者社会性别均为女性,年龄7～25岁,平均14岁。6例患者外阴发育异常;实验室检查促肾上腺皮质激素、睾酮升高;性染色体核型均为46XX;B超检查可见子宫、卵巢,未见睾丸;CT检查双侧肾七腺呈弥漫性、串珠状增生。6例患者均行女性外阴整复术和皮质激素替代治疗。结果：术后外阴外观满意,第二性征接近女性。2例患者术后1个月获得随访,外阴呈正常女性外阴,无尿失禁、尿道阴道瘘等并发症发生。4例患者术后2年复查,月经规律,有自然排卵,毛发浓密粗黑减轻,乳腺较前明显增大,大阴唇开始发育。结论：女性假两性畸形患者应尽早诊冶。外阴整复术和皮质激素替代治疗可使患者获得满意的治疗效果和生活质量。     

先天性肾上腺皮质增生致女性假两性畸形的诊治(附四例报告)

目的　报告 4例先天性肾上腺皮质增生所致女性假两性畸形患者的激素替代治疗加手术整形的效果。　方法　 4例患者 ,年龄分别为 11、15、14、2 0岁。通过病史、超声、血清激素测定及染色体分析 ,确诊为先天性肾上腺皮质增生所致女性假两性畸形 ,利用会阴皮瓣行阴蒂和阴道成形术。　结果　术后短期应用雌孕激素调整月经周期 ,终生服用氢化可的松 (10～ 2 0mg ,bid)替代治疗。术后患者均月经来潮 ,乳房发育 ,阴道通畅未发生缩窄。　结论　此病易误诊为男性尿道下裂并双侧隐睾 ,诊断除详细体检外 ,还应进行血清激素测定、腹部超声检查及染色体分析。合理利用会阴和阴蒂皮瓣再造阴唇、阴道和阴蒂 ,同时加强围手术期处理 ,可以取得较满意的疗效。     

肥大阴蒂缩小成形术治疗女假两性畸形

目的 探讨采用以阴蒂背侧血管神经束为蒂的肥大阴蒂成形术治疗女假两性畸形的临床效果.方法 对2003年7月至2009年6月收治的8例女假两性畸形,采用以阴蒂背侧血管神经束为蒂的肥大阴蒂缩小成形术及阴唇成形术进行会阴女性化的转变.结果 8例患者切口均Ⅰ期愈合,成形之阴蒂头血运良好,大小、形态、位置及感觉均较满意,外阴呈女性...     

Male pseudohermaphroditism presented with sudden cardiac arrest

Torsades de pointes is a life-threatening arrhythmia associated with a number of causes, but is very rare among endocrinologic disorders. We report a case of male pseudohermaphroditism with hyperaldosteronism due to a 17α-hydroxylase deficiency presented with sudden cardiac arrest.     

New mutations, hotspots, and founder effects in Brazilian patients with steroid 5α-reductase deficiency type 2

Mutations of the steroid 5-reductase type 2 (SRD5A2) gene in 46,XY subjects cause masculinization defects of varying degrees, due to reduced or impaired enzymatic activity. In this study, sequence abnormalities of the SRD5A2 gene were assessed by polymerase chain reaction with specific primers and automated sequencing analysis in DNA samples from 20 patients with suspected steroid 5-reductase type 2 deficiency from 18 Brazilian families. Eleven subjects presented SRD5A2 homozygous single-base mutations (two first cousins and four unrelated patients with G183S, two with R246W, one with del642T, one with G196S, and one with 217_218insC plus the A49T variant in heterozygosis), whereas four were compound heterozygotes (one with Q126R/IVS3+1G>A, one with Q126R/del418T, and two brothers with Q126R/G158R). Three patients were heterozygous for A207D, G196S, and R266W substitutions. The V89L polymorphism was found in heterozygosis in one of them (with A207D) and in one case with an otherwise normal gene sequence. The A49T variant was also detected in heterozygosis in the second case without other sequencing abnormalities. Four patients harbor yet non-described SRD5A2 gene mutations: a single nucleotide deletion (del642T), a G158R amino acid substitution, a splice junction mutation (IVS3+1G>A), and the insertion of a cytosine (217_218insC) occurring at a CCCC motif. This is the first report of a single-nucleotide insertion in the coding sequence of the SRD5A2 gene. In addition to these new mutations, this investigation reveals the prevalence of G183S substitution among a subset of African–Brazilian patients and presents evidences of the recurrence of already known mutations.     

Male pseudohermaphroditism in sibs with the α-thalassemia/mental retardation (ATR-X) syndrome

Genital abnormalities have been noted in several patients with the X-linked form of α-thalassemia and mental retardation syndrome (ATR-X). The initial clinical report of the condition documented a phenotypic female with 46,XY karyotype. To this we now add 2 further siblings with abnormalities of the external genitalia, manifesting as male pseudohermaphroditism. © 1995 Wiley-Liss, Inc.     

Prenatal diagnosis of female pseudohermaphroditism associated with bilateral luteoma of pregnancy: case report

Female pseudohermaphroditism associated with luteoma of pregnancy (LP) is a rare condition characterized by varying degrees of masculinization of a female fetus. We describe a case, diagnosed at 13 weeks gestation. Transvaginal ultrasound at 5 weeks of gestation revealed a normal intrauterine gestational sac and an enlarged maternal right ovary. Re-examination at 13 weeks showed a fetus with male external genitalia. Cytogenetic investigation on amniotic fluid revealed a normal female karyotype 46,XX. Follow-up sonography confirmed the previous assignment of male external genitalia and a second amniocentesis was negative for the SRY gene. High levels of androgens were found in the maternal blood. A diagnosis of female pseudohermaphroditism associated with bilateral LP was made. A healthy girl was born by Caesarean section with complete masculinization of external genitalia (Prader V). Histology confirmed a bilateral LP. To the best of our knowledge this represents the first case of prenatal diagnosis of female pseudohermaphroditism associated with LP and demonstrates the feasibility of diagnosis by sonography from 13 weeks gestation. This is also the first case described of Prader V masculinization associated with LP.