الفهرس 
NORMAL SEXUAL DEVELOPMENTOnly 14 pages are availabe for public view
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Abstract
The newborn with abnormal genital development presents a difficult diagnostic and treatment challenge for the pediatrician. Disorders/Differences of Sex Development (DSD) are variety of congenital diseases with anomalies of the sex chromosomes, the gonads, the reproductive ducts and the genitalia. An Egyptian study has reported an incidence of one newborn with ambiguous genitalia per 3000 live births, which is relatively common. According to the latest classification of the Lawson Wilkins Pediatric Endocrine Society (LWPES) and the European Society for Pediatric Endocrinology (ESPE) in 2006, DSD is classified into three main categories: sex chromosome DSD, 46,XY DSD and 46,XX DSD. 46,XY DSD is considered the most common type and is categorized into two major groups: disorders of testicular development and disorders of androgen synthesis, metabolism and action on the target organ.
Testicular development is dependent on genes for testis determination and differentiation and on the pathway of androgen metabolism and action. In the past years, there has been growing evidence that exposure to chemicals and environmental pollutants pose a serious threat to human and animal reproductive organs.
Endocrine Disrupting chemicals (EDCs) are exogenous compounds that are claimed for many sexual development disorders, many of these chemicals (which include pesticides, plasticizers, household products and detergents, pharmaceuticals and industrial chemicals) are now present in nature. In addition, humans are exposed to these chemicals through the food, dust and water via bioaccumulation.
The present study aimed to correlate genotypic abnormalities with the clinical phenotype in 46,XY DSD patients using Multiplex Ligation dependent Probe Amplification (MLPA) technique and to study possible paternal and maternal exposure to environmental risk factors in these cases.
The current study was conducted on 35 patients presented with features of 46,XY DSD as ambiguous genitalia, hypospadius, undescended testis or primary amenorrhea, associated with or without other anomalies from total of 225 DSD patients referred to National Research Centre over period of 3 years.
All patients were subjected to clinical history taking, pedigree analysis, and were subjected to questionnaire for paternal and maternal exposure to environmental risk factors.
Patients underwent thorough clinical examination including genital examination with the classification of the genital phenotype according to Quigley scoring. Pubertal evaluation was performed following Tanner staging. Hormonal assay, pelvic ultrasonography and laparoscopy with gonadal biopsy and histopathological examination were carried out.
Cytogenetic studies, using GTG banding was applied on peripheral blood lymphocytes and showed structural chromosomal abnormalities in three patients and MLPA assay was conducted using the Intersex kit and Gonadal dysgenesis kit.
Clinically significant CNVs were detected in 11% including deletions of DMRT1 gene, SOX9 gene and duplication of HSD17B3 gene. No significant correlation was detected in the current study by maternal and paternal questionnaire for certain environmental risk factors.
MLPA was proved as a useful initial screening tool for DSD patient for detecting abnormalities in certain DSD genes at the exon level, it is advisable to be combined with Sanger sequencing. On the other hand, higher techniques as Comparative Genomic Hybridization and next generation sequencing would be beneficial for identification of pathogenic CNVs all over the genome with a higher diagnostic yield in undiagnosed patients or in patients with complex phenotypes. Further developing methods and better approaches are essential for evaluating associations of environmental exposure risks and health outcome.