Alaa Cheikhelard

Long-Term Followup and Comparison Between Genotype and Phenotype in 29 Cases of Complete Androgen Insensitivity Syndrome

PURPOSE Diagnosis and management of the complete androgen insensitivity syndrome have dramatically changed in the last few decades, with earlier diagnosis and the development of molecular biology. Some phenotypic features such as development of wolffian and mullerian remnants have been suggested to be an index of subtle residual androgen activity. Variations of these features clearly exist among patients and may influence treatment. Our aim was to assess the safety of keeping gonads in place for spontaneous puberty in a cohort of patients with genetically proved complete androgen insensitivity syndrome. In parallel to the risks of virilization at puberty and gonadal tumor some additional features, such as need for vaginal surgery, were investigated. MATERIALS AND METHODS We studied the genotype, phenotype, anatomy of the internal and external genitalia, and clinical outcome of 29 cases of complete androgen insensitivity syndrome, managed by the same team from diagnosis (frequently in early childhood) to adulthood. RESULTS All patients had a complete female phenotype. A total of 19 different mutations (including 7 unreported) were found. Each family presented with a different mutation. No somatic mosaicism was detected. Vas deferens and epididymis were found in all types of mutations (missense, nonsense and frameshift). Of the patients 23 were postpubertal (19 spontaneously). No postpubertal virilization occurred. Only 1 carcinoma in situ was detected (postpubertally). Vaginal surgery was rarely necessary. CONCLUSIONS Our data advocate for keeping the gonads in the complete androgen insensitivity syndrome, at least until completion of spontaneous puberty. The risk of virilization at puberty should be ruled out for each androgen receptor mutation before management decisions and genetic counseling. Vaginal surgery should not be indicated as first line treatment.

HOW ACCURATE IS THE PRENATAL DIAGNOSIS OF ABNORMAL GENITALIA

PURPOSE The prenatal diagnosis of abnormal genitalia may have a major impact on prenatal counseling and postnatal outcome. We studied the accuracy and clinical implications of the prenatal diagnosis of abnormal genitalia. MATERIALS AND METHODS Between 1991 and 1999 the prenatal and/or postnatal diagnosis of abnormal genitalia in 53 cases was made at our institution. All cases were prenatally assessed at our Obstetrics and Fetal Medicine Department. Outcome was confirmed postnatally or by a fetopathologist in the case of pregnancy termination. RESULTS A genital anomaly was prenatally diagnosed in 43 cases and was accurate in 34, while in 9 cases anomalies were absent at birth. In 10 cases ambiguous genitalia were not detected prenatally. The primary anomalies suspected were male pseudohermaphroditism in 19 cases and female pseudohermaphroditism in 12, including 2 cases of congenital adrenal hyperplasia. Male pseudohermaphroditism was detected prenatally in 17 cases and diagnosis was confirmed at birth. Female pseudohermaphroditism was detected prenatally in 12 cases and only 5 were confirmed and the anomaly was discovered at birth in 6. The prognosis was highly altered when many malformations or aneuploidy was associated with ambiguous genitalia. Of the 15 patients with many malformations only 3 survived, and pregnancy was terminated in 3 of 4 cases of aneuploidy. CONCLUSIONS When pseudohermaphroditism was detected in a male fetus by an experienced ultrasonographer at a tertiary center the prenatal diagnosis was accurate in 100% of cases. The prenatal diagnosis was less accurate (46% correct) in a female fetus.

Wandering spleen in children: multicenter retrospective study

Wandering spleen in children is a rare condition. The diagnosis is difficult, and any delay can cause splenic ischemia. An epidemiologic, semiological, and surgical diagnosis questionnaire on incidence of wandering spleen in children was sent to several French surgical teams. We report the results of this multicenter retrospective study. Fourteen cases (6 girls, 8 boys) were reported between 1984 and 2009; the age range varies between 1-day-old and 15 years; 86% were seen in the emergency department. Ninety-three percent had diffuse abdominal pain. For 57% of the cases, it was their first symptomatic episode of this type. No diagnosis was established based on the clinical results alone. All patients had presurgical imaging diagnosis. Open surgery was performed on 64% cases. Forty-three had splenectomy for splenic ischemia. Thirty-six percent had splenopexy, 14% had laparoscopic gastropexy, and 7% had spleen repositioning and regeneration. Complications were noted in 60% of the cases resulting in postsplenopexy splenic ischemia. Early diagnosis and surgery are the best guarantee for spleen preservation. Even if the choice of one technique, splenopexy or gastropexy, can be argued, gastropexy has the advantage of avoiding splenic manipulation and restoring proper physiologic anatomy. When there is no history of abdominal surgery, laparoscopy surgery seems the best procedure.

Bacteriologic epidemiology and empirical treatment of pediatric complicated appendicitis

Preoperative samples in the context of complicated appendicitis (CA) are rarely collected, and there is no consensus regarding the optimal antibiotic therapy in children. To help optimize empirical preoperative treatment, we studied clinical and bacteriologic data from a prospective cohort of 93 children with CA in a French hospital. All the bacteria isolated from peritoneal fluids were identified, using phenotypic and/or molecular techniques. The most commonly recovered species were Escherichia coli (71%), Streptococcus group milleri (34%), anaerobes (20%), and Pseudomonas aeruginosa (19%). The association piperacillin-tazobactam is an accurate choice of empirical therapy as it is active against 97% of bacteria. A third-generation cephalosporin with metronidazole in association with an aminoglycoside is a good alternative. Although antibiotic use may be considered as an adjunct to surgical intervention of CA, the appropriate use of preoperative antibiotics is essential and must be constantly reevaluated according to the bacterial epidemiology.

Hypospadias: Surgery and Complications

The aim of this review is to summarize the various steps of the surgical procedures to treat a hypospadias. Hundreds of procedures have been described but most of them follow the same principles. They include correction of a ventral curvature, the urethroplasty itself and penile skin reconstruction. Most of the affected children may be treated with a one-stage procedure. Each hypospadias surgeon has to know a variety of techniques and tailor the procedure used for each individual child. Complications are frequent after the hypospadias correction. Fistulas are the more frequent of these complications occurring in less than 5% of anterior cases, but up to 50% in posterior cases. Long-term follow-up is mandatory to evaluate the sexual outcome of the adults operated on during childhood for a posterior hypospadias, even if the available data seem reassuring.

Female Epispadias Management: Perineal Urethrocervicoplasty Versus Classical Young-Dees Procedure

PURPOSE We compared the functional results of 1-stage perineal urethrocervicoplasty and vulvoplasty vs the classic Young-Dees procedure for incontinent female epispadias. MATERIALS AND METHODS We treated 14 female patients with incontinent epispadias between 1997 and 2007, of whom 7 each underwent the Young-Dees procedure until 2004 (group 1) and 1-stage urethrocervicoplasty with vulvoplasty through a perineal subsymphyseal approach (group 2). We retrospectively compared patient age at surgery, bladder capacity, continence outcome and postoperative morbidity. RESULTS The groups were comparable except for age at procedure. In group 1 vs 2 surgery was performed at a median age of 6 vs 4 years. In groups 1 and 2 median preoperative bladder capacity was 120 and 100 cc, and mean followup was 8 and 2.5 years, respectively. Six group 1 patients achieved continence, including 5 with overnight continence, but 5 required additional surgery to enhance continence or voiding, including pericervical injections of bulking agents (3), cervicotomy or urethral calibration (4) and enterocystoplasty (1). Two patients required long-term clean intermittent catheterization, 4 underwent upper tract dilation postoperatively and 4 had a total of 8 episodes of febrile urinary tract infection. Six group 2 patients were continent, including 3 with overnight continence (p = 1). None required clean intermittent catheterization even temporarily or any additional surgery (p = 0.02). Only 2 patients had a febrile urinary tract infection (p = 0.25). CONCLUSIONS Reconstructing the bladder neck and urethra via a perineal approach for female epispadias is promising. Surgery may be performed earlier with similar continence results, less postoperative morbidity and less need for additional surgery. Long-term studies are needed to confirm these preliminary results.

Gynecologic clinical examination of the child and adolescent.

Pediatric gynecological examination is very simple, but usually unrecognized by physicians without a specific experience in pediatric gynecology. It is always necessary and most of the time sufficient in children and adolescents consulting for gynecological complaints, endocrine problems, or sexual abuse. However, accurate evidence-based data on its normality is poor in the literature, because of bias represented by the inclusion of abused patients in these studies. Our aim was to describe the preparation to a full gynecological examination, the adequate positions, and the sequence and technique required for a well-accepted and nontraumatic clinical examination. Normal findings are described depending on the age of the patient (child, newborn, adolescent), and are based on evidence from the literature. Indications for vaginoscopy and bacterial sampling are discussed according to the age of the patient. The most important factors in the achievement of a full gynecological examination and a trusting patient-physician relationship are a good anatomical and physiological knowledge of the genital system in children, and the learning of nonaggressive examination technical skills associated with good communication skills. Clinical examination is always necessary and most of the time is sufficient together with the medical history to diagnose and treat the childs gynecological problems. Evidence-based data on normal genital findings is poor in the literature, because many studies include abused children or present bias in the methods of recruitment and assessment of normal girls [1].

Potential determinant factors of sexual identity in ambiguous genitalia

This is a review of literature scanning the potential factors which may affect Sexual Identity (S.I.) and Gender Identity (G.I.) in patients with ambiguous genitalia. Definitions of these concepts are outlined. Genetic, gonadal, hormonal, social and cultural pressures are reviewed as well as lessons to learn from clinical experiences and outcomes. Current criteriae used to assign gender in a child with ambiguous genitalia are discussed including medical and surgical criteriae as well as cultural disruptors. At the dawn of the third millennium, it is remarkable how little we know about the establishment of our individual and social identities.

Complete androgen insensitivity syndrome: diagnosis and management

Complete androgen insensitivity syndrome (CAIS) is an X-linked genetic disorder affecting 46,XY individuals, characterized by the loss of function of the androgen receptor gene resulting in complete peripheral androgen resistance. Patients have a nonambiguous female phenotype with normal female external genitalia. Gonads are undescended testes (either intra-abdominal or inguinal), there is no uterus and the length of the vagina is usually very short. Gender identity is always female. This review focuses on the importance of accurate diagnosis of CAIS versus partial androgen insensitivity syndrome and other disorders of sex development by genotyping the androgen receptor, and raises issues of the optimal management of these patients. In the era of the Consensus Statement on Management of Intersex Disorders, we provide new insights into CAIS screening, surgical management of the gonads (balancing between hormonal production and malignancy risk) and of vaginal adequacy, and the ethics concerned with the disclosure to patients and their families.

Early elimination dysfunction associated with cephalic anomalies: Is there a link?

UNLABELLED Elimination dysfunction in children can be related to three main aetiologies: 1) spinal cord anomalies, 2) social and environmental disorders, and 3) syndromic elimination disorders. From this last group, we report cases of a previously undescribed combination of elimination disorders and cephalic anomalies symptoms which may constitute a proper entity for which conventional treatments may fail. A comprehensive review of congenital elimination disorders is given. PATIENTS AND METHODS Six patients (four boys, two girls) presenting with early elimination dysfunction associated with cephalic anomalies were assessed and treated between 1994 and 2005. None presented with identified lower urinary tract obstruction or spinal cord anomalies. Follow up ranged between 5.5 and 11.5 (mean 6.7) years. RESULTS All six had early elimination disorders, represented by urine retention, urinary tract infections, constipation and soiling. All had facial dysmorphy and cerebral anomalies with developmental delay of varying severity. All had a dilated urinary tract, with severe vesicoureteral reflux in five and one megaureter without reflux. All had abnormal renal isotope scans, two associated with chronic renal failure. The family medical history was significant in some cases. Treatment included early urinary diversion, and there was a high failure rate for ureteral reimplantation. CONCLUSION The combination of congenital elimination dysfunction with facial anomalies, developmental retardation, cephalic anomalies, abnormal urinary tracts, without identified spinal cord disorders or lower urinary tract obstruction, may represent a defined population of children. Identification may lead to early elimination support measures including temporary bladder diversion, Mitrofanoff diversion, alpha blockers and bowel transit medications.