Persistent unexplained congenital clitoromegaly in females born extremely prematurely

Objective: Unexplained clitoromegaly is a rare but well recognised feature in girls born premature. Although detected at birth, girls may re-present during childhood to paediatric urologists and gynaecologists who should be aware of this condition. The aim of the study was to describe the clinical findings and management of a series of girls presenting with persistent congenital clitoromegaly associated with prematurity. / Materials and methods: This was a retrospective notes review set in a tertiary referral centre for Paediatric and Adolescent Gynaecology (PAG). / Results: Eight girls with a mean age of 6 years were seen over an eight year period. In all cases a Disorder of Sex Development (DSD) had been previously excluded. The main symptoms were discomfort or concern about appearance. On examination five girls had excess skin over the clitoris and three had enlarged corporal tissue. Management included reassurance and simple measures to ease discomfort. In two cases the parents requested referral to a paediatric urologist to consider clitoral surgery. / Conclusion: As survival rates for extreme prematurity improve, paediatric urologists and gynaecologists are likely to see more of these cases. Clinicians must be familiar with this condition to ensure children are managed appropriately

Hormone replacement treatment choices in complete androgen insensitivity syndrome: an audit of an adult clinic

OBJECTIVE: To review the treatment choices of women with complete androgen insensitivity syndrome (CAIS) at a single tertiary centre. DESIGN: Retrospective review. PATIENTS: Women with CAIS identified from our database. RESULTS: The study group comprised 141 women with CAIS. Eleven percent (16/141) of women had gonads in situ, 3 of whom were under workup for gonadectomy. The age of gonadectomy in the remainder 125 women was 17 (0.1-53) years. The most common form of HRT was oral oestrogen or transdermal oestrogen in 80% (113/141). 13/141 (9%) women used vaginal oestrogens alone or together with other forms of HRT. Testosterone preparations had been used by 17% (24/141) of women and were currently used in 10% (14/141). Of those who had used testosterone, 42% (10/24) had chosen not to continue after a therapeutic trial. CONCLUSIONS: In a clinic offering individualised multidisciplinary care for women with CAIS, we found that the majority of women chose oestrogen-based treatment while a significant minority used testosterone

Multidisciplinary approach to the management of children with female genital mutilation (FGM) or suspected FGM: service description and case series

OBJECTIVE: To describe the first dedicated clinic in the UK for children with suspected or confirmed female genital mutilation (FGM) including referral patterns, clinical findings and subsequent management. DESIGN AND SETTING: A prospective study of all children seen in a dedicated multidisciplinary FGM clinic for children over a 1-year period. POPULATION: Patients aged under 18 years referred for clinical assessment or for a second opinion on Digital Versatile Disc (DVD) images. METHODS AND MAIN OUTCOME MEASURES: Data were collected on reasons for referral, demography, genital examination findings including FGM type, and clinical recommendations. RESULTS: 38 children were referred of whom 18 (47%) had confirmed FGM; most frequently type 4 (61%). Social care and police referred 78% of cases. According to UK law FGM had been performed illegally in three cases. Anonymous information given to the police led to the referral of six children, none of whom had had FGM. CONCLUSIONS: Mandatory reporting and increased media attention may increase the numbers of referrals of children with suspected FGM. This patient group have complex needs and management in a dedicated multidisciplinary service is essential. Paediatricians and gynaecologists should have the skills to carry out the consultation and detect all types of FGM including type 4 which was the most common type seen in this series. This is the first dedicated FGM service for children in the UK and similar clinics in high-prevalence areas should be established

The long-term management and outcomes of cloacal anomalies.

Cloacal anomalies occur when failure of the urogenital septum to separate the cloacal membrane results in the urethra, vagina, rectum and anus opening into a single common channel. The reported incidence is 1:50,000 live births. Short-term paediatric outcomes of surgery are well reported and survival into adulthood is now usual, but long-term outcome data are less comprehensive. Chronic renal failure is reported to occur in 50 % of patients with cloacal anomalies, and 26-72 % (dependant on the length of the common channel) of patients experience urinary incontinence in adult life. Defaecation is normal in 53 % of patients, with some managed by methods other than surgery, including medication, washouts, stoma and antegrade continent enema. Gynaecological anomalies are common and can necessitate reconstructive surgery at adolescence for menstrual obstruction. No data are currently available on sexual function and little on the quality of life. Pregnancy is extremely rare and highly risky. Patient care should be provided by a multidisciplinary team with experience in managing these and other related complex congenital malformations. However, there is an urgent need for a well-planned, collaborative multicentre prospective study on the urological, gastrointestinal and gynaecological aspects of this rare group of complex conditions

Holistic management of DSD

Disorder of sex development (DSD) presents a unique challenge, both diagnostically and in terms of acute and longer-term management. These are relatively rare conditions usually requiring a multidisciplinary approach from the outset and the involvement of a tertiary centre for assessment and management recommendations. This article describes the structure of the multidisciplinary team (MDT) at our centre, with contributions from key members of the team regarding their individual roles. The focus is on the newborn referred for assessment of ambiguous genitalia, rather than on individuals who present in the adolescent period or at other times, although the same MDT involvement is likely to be required. The approach to the initial assessment and management is discussed and the subsequent diagnosis and follow-up presented, with emphasis on the importance of careful transition and long-term support

Childhood surgery for ambiguous genitalia: glimpses of practice changes or more of the same?

The Chicago consensus statement of 2005 was created at the point of cumulative criticisms and debates around the clinical practice of childhood genital surgery. It was drawn up at a time when it had become clearer that medically non-essential paediatric genital operations were associated with poor adult cosmetic outcomes and sexual functioning. However, data were not available for non-intervention. Therefore, parents and clinicians had no reliable information on how a child growing up with atypical genitalia might fare. The most positive recommendation in the consensus statement was the strong recommendation for decisions to be reached by a multidisciplinary team in collaboration with affected families. Importantly, the value of user groups was likewise formally acknowledged. For many services, there has been a sea change in the way surgeons work. Whilst some surgeons may continue with the standard practice of childhood genital surgery, it is becoming clearer that with adequate support, more individuals and families choose to postpone elective interventions. However, these are our observations only. Authoritative evidence must be based on high-quality multi-centre multidisciplinary research to prospectively monitor the long-term multiple outcomes of surgery and no surgery. There is as yet no obvious move towards such an endeavour. © Taylor & Francis

Epidemiological surveillance study of female genital mutilation in the UK

OBJECTIVES: Describe cases of female genital mutilation (FGM) presenting to consultant paediatricians and sexual assault referral centres (SARCs), including demographics, medical symptoms, examination findings and outcome. DESIGN: The well-established epidemiological surveillance study performed through the British Paediatric Surveillance Unit included FGM on the monthly returns. SETTING: All consultant paediatricians and relevant SARC leads across the UK and Ireland. PATIENTS: Under 16 years old with FGM. INTERVENTIONS: Data on cases from November 2015 to November 2017 and 12 months later meeting the case definition of FGM. MAIN OUTCOMES MEASURES: Returns included 146 cases, 103 (71%) had confirmed FGM and 43 (29%) did not meet the case definition. There were none from Northern Ireland. RESULTS: The mean reported age was 3 years. Using the WHO classification of FGM, 58% (n=60) had either type 1 or type 2, 8% (n=8) had type 3 and 21% (n=22) had type 4. 13% (n=13) of the cases were not classified and none had piercings or labiaplasty. The majority, 70% had FGM performed in Africa with others from Europe, Middle East and South-East Asia. There were few physical and mental health symptoms. Only one case resulted in a successful prosecution. CONCLUSIONS: There were low numbers of children presenting with FGM and in the 2 years there was only one prosecution. The findings may be consistent with attitude changes in FGM practising communities and those at risk should be protected and supported by culturally competent national policie

Exoanal ultrasound of the anal sphincter: normal anatomy and sphincter defects

To describe the sonographic appearance of normal anal sphincter anatomy and sphincter defects evaluated with a conventional 5 MHz convex transducer placed on the perineum. Design Prospective, single-blind study. Setting Department of Obstetrics and Gynecology, University of Michigan Medical Center, USA. Population Twenty-five women with symptoms of faecal incontinence, 11 asymptomatic nulliparous women, and 32 asymptomatic parous women. Methods A convex scanner was placed on the perineum with the woman in lithotomy position. Images were taken at three levels of the sphincter canal. Pictures were evaluated by two examiners who were blinded to the case history of the women and to the results of each other for the presence or absence of sphincter defects. Main outcome measures Description of anal sphincter appearance on endoanal ultrasound. Reproducibilty of the evaluation of sphincter defects. Results The internal anal sphincter is visible as a hypoechoic circle; the external anal sphincter shows a hyperechoic pattern. Proximally the sling of the puborectalis muscle is visible. Sphincter defects were detected in 20 women. In all five women who subsequently underwent surgery, the presence and location of the defect was confirmed at the time of surgery. Examiners were in agreement 100% of the time on the presence or absence of internal defects. They disagreed in one patient on the presence of an external defect. Conclusion Exoanal ultrasound provides information on normal anatomy and on defects of the anal sphincter.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75125/1/j.1471-0528.1997.tb12056.x.pd

Multiple Oncogenic Pathway Signatures Show Coordinate Expression Patterns in Human Prostate Tumors

BACKGROUND: Gene transcription patterns associated with activation of oncogenes Myc, c-Src, beta-catenin, E2F3, H-Ras, HER2, EGFR, MEK, Raf, MAPK, Akt, and cyclin D1, as well as of the cell cycle and of androgen signaling have been generated in previous studies using experimental models. It was not clear whether genes in these "oncogenic signatures" would show coordinate expression patterns in human prostate tumors, particularly as most of the signatures were derived from cell types other than prostate. PRINCIPAL FINDINGS: The above oncogenic pathway signatures were examined in four different gene expression profile datasets of human prostate tumors (representing approximately 250 patients in all), using both Q1-Q2 and one-sided Fisher's exact enrichment analysis methods. A significant fraction (approximately 5%) of genes up-regulated experimentally by Myc, c-Src, HER2, Akt, or androgen were co-expressed in human tumors with the oncogene or biomarker corresponding to the pathway signature. Genes down-regulated experimentally, however, did not show anticipated patterns of anti-enrichment in the human tumors. CONCLUSIONS: Significant subsets of the genes in these experimentally-derived oncogenic signatures are relevant to the study of human prostate cancer. Both molecular biologists and clinical researchers could focus attention on the relatively small number of genes identified here as having coordinate patterns that arise from both the experimental system and the human disease system

BFAST: An Alignment Tool for Large Scale Genome Resequencing

BACKGROUND:The new generation of massively parallel DNA sequencers, combined with the challenge of whole human genome resequencing, result in the need for rapid and accurate alignment of billions of short DNA sequence reads to a large reference genome. Speed is obviously of great importance, but equally important is maintaining alignment accuracy of short reads, in the 25-100 base range, in the presence of errors and true biological variation. METHODOLOGY:We introduce a new algorithm specifically optimized for this task, as well as a freely available implementation, BFAST, which can align data produced by any of current sequencing platforms, allows for user-customizable levels of speed and accuracy, supports paired end data, and provides for efficient parallel and multi-threaded computation on a computer cluster. The new method is based on creating flexible, efficient whole genome indexes to rapidly map reads to candidate alignment locations, with arbitrary multiple independent indexes allowed to achieve robustness against read errors and sequence variants. The final local alignment uses a Smith-Waterman method, with gaps to support the detection of small indels. CONCLUSIONS:We compare BFAST to a selection of large-scale alignment tools -- BLAT, MAQ, SHRiMP, and SOAP -- in terms of both speed and accuracy, using simulated and real-world datasets. We show BFAST can achieve substantially greater sensitivity of alignment in the context of errors and true variants, especially insertions and deletions, and minimize false mappings, while maintaining adequate speed compared to other current methods. We show BFAST can align the amount of data needed to fully resequence a human genome, one billion reads, with high sensitivity and accuracy, on a modest computer cluster in less than 24 hours. BFAST is available at (http://bfast.sourceforge.net)