الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Disorders of sex development are defined as congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical, which may be recognized immediately after birth or later in life. They include a wide spectrum of phenotypes: 46, XY DSD (gonadal dysgenesis or undermasculinisation due to defects in androgen synthesis or action), 46, XX DSD (gonadal dysgenesis or more commonly virilisation due to prenatal or postnatal excess androgen exposure) and sex chromosome DSD. Optimal care of patients with DSD requires a multidisciplinary team and begins in the newborn period. A family history, prenatal history, a general physical examination with attention to any associated dysmorphic features and an assessment of the genital anatomy are the first steps towards a correct diagnosis. The diagnostic evaluation of DSD includes hormone measurements, imaging, cytogenetic and molecular studies for mutations (SRY, SF1, SOX9 and others). The aim of this study was clinical assessment of pediatric patients with ambiguous genitalia, genetic studies including karyotyping, molecular studies for SRY and SOX9 genes and finally genetic counseling for the patients and their families. Our study was conducted in the period from 2012 to 2014; cases were obtained from the Genetic and Endocrinology unit, Pediatric department, Faculty of Medicine, Menoufiya University. During this study, sixteen cases were studied including seven apparent female cases and nine apparent male cases. Their ages ranged from one day to 6 years old. All cases were subjected to the following: I. Detailed history. Summary 136 II. Thorough physical examination. III. Laboratory studies: Routine studies: CBC, serum Na and K levels and RBS. Hormonal studies: Serum 17- OHP, cortisol, ACTH levels and others according to need. IV. Imaging studies: abdomino-pelvic ultrasound, CT ± MRI and others according to need. V. Genetic counseling. VI. Cytogenetic studies especially karyotyping using G banding technique. VII. Molecular studies in the genetic lab of our unit, including: a) DNA extraction from blood samples. b) Polymerase chain reaction (PCR) for SRY and SOX9 genes. c) Gel electrophoresis. In our study, we had sixteen cases varied in age of presentation from one day to 11 months old. Presenting manifestations included ambiguous external genitalia recurrent vomiting and dehydration attacks (salt-losing crisis) in three cases (two females and one male), abnormal body hair growth in two female cases, abnormal body pigmentations in one female case, and abnormal urine stream in two apparent male cases. The history revealed that seven cases had a positive consanguinity, and this represents 43.75 % of cases. In addition, cases number (14 & 15) were cousins, so the high prevalence of consanguinity in our cases represented a significant risk factor in our study. In addition, family pedigree showed that six cases had possible similar conditions in their families (four of them with CAH), and this confirmed importance of family pedigree in suspecting a genetic cause of DSD. In addition, the history revealed occurrence of multiple abortions in relation to advanced maternal and paternal ages. Summary 137 As for the anthropometric measurements, all cases were within normal ranges except four cases were below 3rd percentile for weight and < -2 SD for BMI, and only three of them below 3rd percentile for length. Regarding local examination, the external genital findings of the female patients were mainly clitoromegaly and fused labia, with no palpable gonads and two of them had abnormal pubic hair growth, scaling on Prader system: 1, 2 and 4. For male patients, findings were mainly bifid scrotum and urethral opening at phallus base. Three cases had microphallus. Two only had only one palpable gonad and one case looked apparently like female, case number (12). In addition, the EMS for all was below 11. As regard Tanner staging system, all cases are in prepubertal stages except two female cases number (4 &16) with P2. Regarding serum electrolyte levels, all cases were within normal levels except for three cases (2, 12 & 14) who suffered salt losing crisis, had hyperkalemia and hyponatremia, and only two of them (12 & 14) suffered hypoglycemia. Regarding the imaging studies of the studied group, using abdominopelvic ultrasound ± CT or MRI, eight cases with apparent female phenotype had normal Mullerian structures and gonads except case number (7) had bilateral pelvic streak gonads. Nine cases with apparent male phenotype showed no internal female genitalia and normal scrotal gonads except for three cases, two had right inguinal gonads and one had left inguinal streak gonad. As regard hormonal studies, we focused on assessing adrenal functions, and we found that five cases were above normal ranges for serum 17-OH progesterone levels and two cases were below normal ranges. from these seven cases, six cases had elevated serum ACTH levels and low serum cortisol levels. Summary 138 In addition, five of them showed elevated serum adrenal androgen levels, and other two showed decreased these levels. Karyotyping of the cases revealed six cases with female (46, XX) DSD, eight cases with male (46, XY) DSD and two cases with sex chromosome DSD (one had 45, X and another one with 45, X / 46, XY). Regarding molecular study, we detected SRY gene bands at 418 bp position in studied genetically male cases except patient number (7) which had a karyotype of 45, X/ 46, XY (deleted SRY for this patient). For studied genetically female cases, no SRY gene bands were detected except patient number (6) which had a karyotype of 45, X (translocated SRY for this patient). In addition, the results demonstrated presence of SOX9 gene nearly at 270 bp position in relation to reading frame of DNA ladder in all cases, and no deletions for SOX9 gene were detected in our studied cases. As regard diagnosis, seven patients had CAH, one with 5 α reductase deficiency, 45, X male syndrome for one patient, one patient with mixed gonadal dysgenesis, penioscrotal hypospadias for five patients and one patient with idiopathic hirsutism. Treatment of studied cases involved genetic counseling with parents as regard disease nature, available options especially optimal gender for their offspring, long-term outcomes and how to follow up. Treatment of cases with CAH including lifetime hormonal replacement therapy and salt losing crisis management if occurred. Sex hormonal therapy if needed as in cases of 5- α reductase deficiency, those with micropenis and with delayed pubertal changes. At last, the surgical options and the timing of the operation need to be individualized according to the complexity of the case, associated medical condition and experience of the surgeon.