Disorders of sex development

Disorders of sex development (DSD) occur in 1–2/10,000 live births, with a specific molecular diagnosis only possible in 20% of cases. Presentation is usually at birth, and gender assignment must be avoided before review by an expert multidisciplinary team. Initial investigations allow a working diagnosis to be made within 48 hours. In 46,XY DSD, surgery may be necessary to correct hypospadias, reposition or remove undescended testes, and remove symptomatic Mullerian remnants. In 46,XX DSD, feminizing surgery is performed less frequently than in the past, but genitoplasty may still be indicated. Psychosocial support is required to promote positive adaptation as gender dissatisfaction can occur in certain conditions. Long-term outcome data are sparse.     

Disorders of sex development

Disorders of sex development (DSD) occur in 1–2/10,000 live births, with a specific molecular diagnosis only possible in 20% of cases. Presentation is usually at birth, and gender assignment must be avoided before review by an expert multidisciplinary team. Initial investigations allow a working diagnosis to be made within 48 hours. In 46,XY DSD, surgery may be necessary to correct hypospadias, reposition or remove undescended testes, and remove symptomatic Mullerian remnants. In 46,XX DSD, feminizing surgery is performed less frequently than in the past, but genitoplasty may still be indicated. Psychosocial support is required to promote positive adaptation as gender dissatisfaction can occur in certain conditions. Long-term outcome data are sparse.     

Disorders of sex development

Disorders of sex development (DSD) occur in 1–2/10,000 live births, with a specific molecular diagnosis only possible in 20% of cases. Presentation is usually at birth, and gender assignment must be avoided before review by an expert multidisciplinary team. Initial investigations allow a working diagnosis to be made within 48 hours. In 46,XY DSD, surgery may be necessary to correct hypospadias, reposition or remove undescended testes, and remove symptomatic Müllerian remnants. In 46,XX DSD, feminizing surgery is performed less frequently than in the past, but genitoplasty may still be indicated. Psychosocial support is required to promote positive adaptation as gender dissatisfaction can occur in certain conditions. Long-term outcome data are sparse.     

Disorders of sex development

Disorders of sex development (DSD) occur in 1–2/10,000 live births, with a specific molecular diagnosis only possible in 20% of cases. Presentation is usually at birth, and gender assignment must be avoided before review by an expert multidisciplinary team. Initial investigations allow a working diagnosis to be made within 48 hours. In 46,XY DSD, surgery may be necessary to correct hypospadias, reposition or remove undescended testes, and remove symptomatic Mullerian remnants. In 46,XX DSD, feminizing surgery is performed less frequently than in the past, but genitoplasty may still be indicated. Psychosocial support is required to promote positive adaptation as gender dissatisfaction can occur in certain conditions. Long-term outcome data are sparse.     

Incidence and diagnoses of disorders of sex development in proximal hypospadias

Background

Evidence-based guidelines on evaluation of boys with proximal hypospadias for the possibility of a disorder of sex development (DSD) have yet to be developed. We aimed to investigate the incidence and diagnoses of DSD in patients with proximal hypospadias.

Molecular investigation of mutations in androgen receptor and 5‐alpha‐reductase‐2 genes in 46,XY Disorders of Sex Development with normal testicular development

In this study, we aimed to determine androgen receptor (AR) and SRD5A2 gene mutations in 45 patients characterised by 46,XY Disorders of Sex Differentiation (DSD) signs with normal testicular development referred to the Children's Medical Center from February 2015 to September 2017. Karyotype and sex hormone analyses were performed. Cytogenetic investigation showed that seven patients were 46,XX DSD, six patients were chromosomal DSD and 32 patients were 46,XY DSD. Eight exons of the AR gene and five exons of the SRD5A2 gene were amplified. Two cases were affected with androgen insensitivity syndrome (AIS) (missense mutation on exon 7, position c.3637 G>A: p.R841H and position c.3610 G>A: p.R832Q), one case was affected with 5‐alpha‐reductase deficiency type 2 (missense mutation at c.578A>G: p.N193S on exon 4), and 22 cases (88%) did not demonstrate AIS or 5α‐RD2 gene abnormality. Due to the great impact of these disorders on human lifestyle, evaluation of genes involved can improve genetic counselling and therapeutic management. We focused on the AR and SRD5A2 genes in patients with 46,XY DSDs with normal testicular development referred to the Children's Medical Center from all over the country to eventually culminate in a reliable prenatal diagnosis protocol at this major referral centre giving service to a great number of families with consanguineous marriages.     

Long‐term outcome of ovotesticular disorder of sex development: A single center experience

Objectives: To describe the clinical features of children with ovotesticular disorder of sex development (DSD) and to review cases of ovotesticular DSD in Japan. Methods: Medical records of eight children diagnosed with ovotesticular DSD at our institute during the past 17 years were retrospectively evaluated. A review of 165 reported cases of ovotesticular DSD from Japanese institutions was carried out. Results: Mean follow up was 8.2 years for six children, with two children lost to follow up. Mean age at first presentation was 2.4 months. All children were Japanese. The most common initial manifestation was ambiguous genitalia. The female : male ratio as the sex of rearing was 1:1. Gender reassignment, from male to female, was carried out in one child at 4‐months‐old. Genital surgery was always carried out in early childhood as per family desire. Appropriate gonadal tissue was preserved except for one child. No gonadal tumors were detected during follow up. Spontaneous pubertal development occurred in one boy. In reviewing Japanese data, the frequency of testes was higher than in other ethnicities and this was related to the higher incidence of 46,XY. Conclusions: According to our experience, most families in Japan desire early genital surgery in the case of ovotesticular DSD. Chromosomal and gonadal distributions in patients with ovotesticular DSD differ between Japanese and other ethnic groups. Treatment for these patients needs to be provided after considering the cultural and social backgrounds of DSD in Japan.     

Long-term physical, hormonal, and sexual outcome of males with disorders of sex development

Purpose

We investigated the long-term physical, hormonal, and sexual outcomes of males with disorders of sex development (DSD) and discussed the necessity of long-term follow-up for these patients after surgery.

Patients and Method

Twelve DSD patients (average age, 21.0 ± 3.6 years old) who had been designated as male in childhood (3 ovotesticular DSD, four 45,XO/46,XY mixed gonadal dysgenesis, four 46,XX testicular DSD, and one 46,XY DSD; androgen insensitivity syndrome) were enrolled. For these patients, height, penile length, and testicular volume were evaluated in adulthood. Serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone were also measured during follow-up. In addition, sexual function and romantic relationships were evaluated.

Results

Development of the penis and testes was poor. According to the hormonal study, these patients were diagnosed with hypergonadotropic hypogonadism or normogonadism; 90% patients had experienced penile erection and masturbation at the time of participation, and 70% and 40% patients had experienced ejaculation and sexual intercourse with female partners, respectively. No patients preferred to avoid sexual contact with women.

Conclusion

Although DSD males had an undeveloped penis and testis and had hypergonadotropic hypogonadism or normogonadism, most had male sexual potential and male sex identity as long as testicular tissues were preserved.     

小儿卵睾性性发育疾病的诊治(附9例报告)

目的:分析探讨小儿卵睾性性发育疾病的诊断及治疗。方法:回顾分析我院泌尿外科收治的卵睾性性发育疾病患儿共9例,分析其临床表现、诊断及治疗方法。结果:9例卵睾性性发育疾病患儿,初诊年龄为9个月至9岁,社会性别男性7例,女性2例,核型46,XX4例,46,XX/46,XY2例,46,XY1例,其余2例无染色体资料。临床多以出生后外生殖器畸形就诊,男性表现为会阴型或阴茎阴囊型尿道下裂,伴或不伴隐睾,女性有阴蒂肥大,外阴畸形。所有患儿均经性腺活检明确诊断,通过手术切除与抚养性别不符的性腺,矫正外生殖器畸形。结论:卵睾性性发育疾病最终性别的选择主要根据外生殖器的发育情况,结合性腺分化、染色体核型和内生殖器的结构以及家属的意愿综合考虑决定。腹腔镜技术在卵睾性性发育疾病的盆腔性腺探查活检和切除及睾丸下降固定等方面与传统手术相比具有优势。     

Sexuelle Differenzierungsstörungen und proximale Hypospadie

Background

Children with ambiguous genitalia due to different chromosome or gonadal sex are a particular challenge concerning the diagnostic and therapeutic implications. Proximal hypospadias patients with normal gonadal development should be distinguished from children with DSD (disorders of sex development) to guarantee normal gender identity and the best possible surgical therapy.

Objectives

This paper focuses on the terminology, embryology, and pathophysiology of the different manifestations of DSD. The state of knowledge about this disease pattern with particular emphasis on proximal hypospadias based on national and international scientific discussions is presented.

Materials and methods

The different clinical pictures as well as therapeutic options of DSD with a special focus on recent literature and giving particular attention to patients with proximal hypospadias are presented.

Results

Because of the complexity of patients suffering from disorders of sex development an interdisciplinary DSD healthcare team including a paediatric endocrinologist as well as paediatric urologist should be provided. These specialists enable an accurate diagnosis in severe hypospadias patients without reference to DSD diseases patterns.

     

卵巢睾丸性性发育异常中性腺优势与内生殖器生育潜能——22例病例报告及文献复习

目的探讨卵巢睾丸性性发育异常(OT-DSD)患者的性腺优势和内生殖器潜能。方法回顾性分析北京协和医院1977年3月至2019年8月收治的22例OT-DSD患者的临床资料,着重对其性腺及内生殖器的发育进行比对;并对同期中文文献中的242例相关病例进行汇总分析,对国外新近相关文献进行复习。结果OT-DSD患者最常见的染色体核型是46,XX,本院22例患者中占68.2%(12/22),国内文献资料中占60.8%(132/217);性腺的占比排序为:卵睾>卵巢>睾丸(约4∶3∶3);国内文献中患者资料汇总分析的性腺组合的排序为:分侧型(卵巢-睾丸45.1%)、单侧性(卵睾-卵巢17.4%和卵睾-睾丸13.0%)、双侧性(卵睾-卵睾24.5%)。本院的全部病例和国内文献中的绝大多数病例均有子宫,睾丸侧无子宫发育,卵巢和卵睾侧均有子宫发育,但常显示发育不良,且约半数(11/22例)合并无阴道或尿生殖窦异常。在社会性别为女性的19例患者中,5例因生殖道梗阻行子宫切除,9例阴道发育不良,3例发生卵巢早衰(POF),仅2例完成生育。结论OT-DSD是体现单侧性腺决定内生殖器发育的典型模型,卵睾侧也有子宫发育,患者的内生殖器以女性特征占优势,在性别认定上偏重女性倾向可能更合理,但同时合并生殖道畸形和POF的亦不少见。     

Diagnosing detrusor sphincter dyssynergia in the neurological patient

Detrusor sphincter dyssynergia (DSD) is variant of neurogenic bladder dysfunction caused by suprasacral neurological abnormalities and may be associated with serious complications if unrecognised. This paper focuses on the clinical features as well as challenges and limitations in the diagnosis of DSD.     

46,XY性发育疾病的研究进展

46,XY性发育疾病是临床上一类复杂问题,不仅涉及医疗,也关系着社会、伦理等诸多方面,是一个需要长期甚至终生进行身心随访和诊治的疾病。如能早期诊断、合理治疗,不但可使患者第二性征适当发育,而且可有效防止性腺恶变的可能。近年来由于环境污染等因素的影响,46,XY性发育疾病的发生率在全球范围呈上升趋势,临床应加深对其的认识并提高警惕,及早诊治,最大程度地改善患者预后。本文结合其病因、新分类及诊疗方面的研究现状作一综述。     

性发育异常性腺肿瘤患者术后生存质量评估研究

目的评估性发育异常(DSD)性腺肿瘤患者术后生存质量(QOL),以期对该疾病的长期健康管理提供参考。方法对2006年1月至2015年12月北京协和医院妇产科收治的24例DSD肿瘤患者进行术后随访并提供心理支持,使用WHOQOL-BREF量表(包含生理领域、心理领域、社会关系领域、环境领域4部分)评估QOL。结果 DSD肿瘤患者初治平均年龄为(19.25±4.75)岁(13~29岁),社会性别均为女性,术后均规律随访(4.79±2.36)年(1~10年)至今。纳入15例(62.50%)46,XY单纯性腺发育不全(46,XY PGD),6例(25.00%)雄激素不敏感综合征(AIS),3例(12.50%)XO/XY性腺发育不全(Mixed GD),各疾病类型DSD肿瘤患者QOL心理领域评分均低于其他领域,Mixed GD心理领域评分最低。DSD肿瘤患者QOL评分高于一般DSD患者及一般成年城市人口,差异有统计学意义(P0.05)。患者中良性肿瘤11例,恶性肿瘤13例,两组间QOL评分比较,差异无统计学意义(P0.05)。结论通过接受长期的、个体化的、优化的手术药物治疗和心理支持,DSD肿瘤患者可获得较理想的QOL。     

Awake spinal anesthesia facilitates spine surgery in poor surgical candidates: A case series

BackgroundAnnually, hundreds of thousands of patients undergo surgery for degenerative spine disease (DSD). This represents only a fraction of patients that present for surgical consideration. Procedures are often avoided due to comorbidities that make patients poor candidates for general anesthesia (GA) and its associated risks. With increasing interest in awake surgery under spinal anesthesia (SA), the authors have observed that SA may facilitate spine surgery in patients with relative contraindications to GA. With this in mind, the authors set out to summarize the outcomes of a series of highly comorbid patients who received surgery under SA.MethodsCase logs of a single surgeon were reviewed, and patients undergoing spine surgery under SA were identified. Within this group, patients were identified with relative contraindications to GA, such as advanced age and medical comorbidities. For these patients, for whom surgery was facilitated by SA, the medical records were consulted to report demographic information and patient outcomes.ResultsTen highly comorbid patients were identified who received lumbar spine surgery for DSD under SA. Comorbidities included octogenarian status, obesity, and chronic health conditions such as heart disease. The cohort had a mean age of 75.5 and a mean American Society of Anesthesiologists Physical Status (ASA-PS) score of 3.1. The patients were predicted to have a 2.74-fold increase of serious complications compared to the average patient. There were no adverse events.ConclusionFor patients with symptomatic, refractory DSD and relative contraindications to GA, SA may facilitate safe surgical intervention with excellent outcomes.     

Memokath stents for the treatment of detrusor sphincter dyssynergia (DSD) in men with spinal cord injury: the Princess Royal Spinal Injuries Unit 10-year experience

STUDY DESIGN: Medical records review. OBJECTIVE: To assess the effectiveness of the Memokath (Engineers and Doctors A/S, Denmark) thermosensitive stent as a 'nondestructive' means of reducing bladder outlet resistance by treating detrusor sphincter dyssynergia (DSD) of neurogenic bladder dysfunction associated with spinal cord injury. SETTING: Spinal Injuries Unit, Sheffield, England. METHODS: A medical records review was performed to examine our experience of Memokaths over the last 10 years. During this time, 29 patients with spinal cord injury (17 tetraplegic and 12 paraplegic) underwent stenting of the external urethral sphincter either for prevention of dysreflexic symptoms, high residual urine volumes and subsequent urinary tract infection (UTI) or for protection of the upper tracts. RESULTS: A total of 33 stents were inserted into 29 men (25-77 years) with suprasacral spinal cord injury. Initial results showed that the Memokath was effective in almost all for relief of dysreflexic symptoms and elimination of DSD on pressure flow urodynamics. However, to date, 30 of the 33 stents have been removed. The overall mean working life of the Memokath was 21 months. Four stents were removed electively and 23 for complications, which included stent migration (seven) and blockage (14). Single-ended stents were more prone to migration, which was rare after 1 year (1-13 months, median 3 months, mean 5.5 months). Stent blockage by encrustation or prostatic ingrowth did not occur before 12 months (12-45 months, median 30, mean 27.9 months). CONCLUSIONS: In selected patients, temporary, thermo-expandable (Memokath) stents are effective in the treatment of DSD. The 'working life' of a Memokath stent is 21 months; however, complications do occur which may necessitate removal. Our overall experience with Memokath stents was disappointing. In future, Memokath stents will only be inserted after careful consideration in patients with prior 'failed' transurethral sphincterotomy or with caution in patients suitable for reconstructive surgery.     

Dressing size and pain: a prospective trial

Background: Pain is a personal, subjective experience. In the postoperative period, pain may be influenced by patient, pharmacological and environmental factors. In surgery the aim is to reduce pain in this period by educating patients and using adequate anal­gesia. The aim of the present study was to assess the effect of perceived wound size on pain, as indicated by wound dressing, in the immediate postoperative period. Methods: Patients undergoing appendicectomy were randomized into a group having a dressing the same size (SSD) as the sur­gical wound or double the size (DSD) of the wound. Patients’ pain perception and analgesic requirements were then recorded and analysed to compare the two groups. Results: Both groups had similar results when comparing pain perception. The median total pain score for the SSD and DSD groups at 12 and 24 h postoperatively revealed no statistically significant difference (P > 0.05). Conclusion: The data do not support the hypothesis that postoperative pain may be altered by perceived wound dressing size. Dressing size does not appear to be a variable that could easily be altered to reduce postoperative pain in surgical patients.     

Vaginal revision of intravesical tension-free vaginal tape 44 h after initial placement: a case report

Unintentional cystotomy is a known complication of the tension-free vaginal tape procedure and is commonly diagnosed intraoperatively. Delayed diagnosis does occur and various reparative techniques have been described, some requiring laparotomy with intentional cystotomy and repair. We report a case where a 46-year-old woman underwent vaginal reconstructive surgery including placement of a tension-free vaginal tape, which was complicated by unilateral cystotomy. A delayed diagnosis of intravesical tape placement was made requiring reoperation. The patient underwent a minimally invasive transvaginal procedure for removal and immediate replacement of the malpositioned arm of the tape. We conclude that a transvaginal approach may be an acceptable technique for revision and replacement of the tension-free vaginal tape where cystotomy is identified within 44 h after the initial procedure. With this technique, a more invasive surgery including laparotomy with cystotomy might successfully be avoided.