Cytogenetic and Molecular Studies of Sudanese Patients with Intersex disorders

Abstract

Introduction Sexual differentiation disorders (intersex) occur approximately once in every 4,500 births, and may present in several forms including male and female pseudohermaphroditism, gonadal dysgenesis, and true hermaphroditism. Diagnosis and management of such patients remains controversial challenge that requires highly specialized, multidisciplinary, and well trained team. The work-up of intersex patients comprise the defining of their genetic (chromosomal), gonadal (hormonal), phenotypic, and psychological aspects. The real magnitude of intersex is not yet fully known in Sudan, but hospitals registries indicate clear increased in the number of new cases. The present study aimed to explore and characterize the cytogenetics and molecular alterations, hormonal profile, imaging, and clinical aspects of different types of intersex in Sudanese patients. It aimed also to introduce cytogenetic and molecular techniques in clinical diagnosis of patients with ambiguous genitalia, and to initiate a multidisciplinary working group that can shoulder the responsibility of the diagnosis, management, and postoperative care of intersex patients in Sudan. Material and methods The present study comprised 70 intersex patients; 18 were raised as males (aged 49 days - 32 years), 52 as females (aged 7 days - 34 years), all were referred with provisional diagnosis of intersex during January 2004 and March 2006. For all patients detailed medical history and physical examination were done. In addition to that, short term culturing of patients’ lymphocytes and chromosomal analysis using Wright stain, PCR and agarose gel electrophoresis of genomic DNA for SRY gene, hormonal profile, abdominal and pelvis ultrasound, laparoscopic examination when needed, histopathology examination, and for adult patients psychological assessment to determine the gender and sex orientation were performed. Results Of the 70 intersex patients enrolled in the present study 18 were reared as males (26%); age ranging between 49 days and 32 years (mean 16 years), 52 as females (74%); age ranging between 7 days and 34 years (mean 17 years). The age groups most commonly involved were those patients above 17 years representing 40% of all cases, followed by those with age less than 2 years representing 33%, and those with age ranging between 2 and 17 years accounting for 27% of all intersex cases. The tribal origin analysis indicated Jaaliyin tribe as the most common Sudanese tribe, accounting for 19% followed by Dar-Hamed and Shaigiyah; each accounts for 4% of all intersex patients. Half of the patients have been referred due to genital ambiguity, other complains such as primary or secondary amenorrhea, failure to thrive, and short stature were reported. The psychological assessment revealed that, 13 patients (19%) were satisfied with their sex of rearing, whereas 5 patients (6%) were not satisfied, 16 patients (23%) could not decide, and the remaining 36 patients (51%) were children and thus no assessment has been performed. Out of the 70 patients included in the present study final clinical diagnosis was reached in 55 patients. Of those, 23 patients were diagnosed as male pseudohermaphrodites, 2 patients as testicular feminization syndrome, 14 patients as complete gonadal dysgenesis syndrome, 8 patients as female pseudohermaphrodites, 6 patients as true hermaphrodites, and 2 patients as Smith- Lemli-Opitz syndrome, and Down’s syndrome that associated with ambiguous. The clinical diagnosis on the remaining 15 was still under controversial till the end of the present study. Conclusions Multidisciplinary approach that involves neonatologists, geneticists, endocrinologists, pediatric surgeons, experienced radiologists, pathologists and molecular biologists remains the best approach for diagnosis and management of intersex patients. Involvement of individuals other than health personal (lawyers, social workers, and religious men) is extremely important for proper management and post sex and/or gender assignment period. Recognition and early diagnosis of sexual differentiation disorders depends mainly on the labor-attendance staff (Midwifes). Thus more effort should be directed to train midwifes in how to examine, correctly, the external genitalia of the new born. Psychological assessment and psychotherapy of intersex patients are crucial before any sex assignment or surgical procedure. Female genital mutilation (FGM) is still widely practiced and if FGM is performed in intersex patients e.g., male pseudohermaphrodites, it leads to life long felony. According to the data in the present study most of the patients were from low or medium social class, and hence can not afford the extensive and expensive process of diagnosis and management of their conditions, thus a non-profitable scientific multidisciplinary body should comes foreword and shoulder this responsibility. Unfortunately there is no what so ever legal guidelines and thus legal frame for diagnosis and management of intersex conditions is badly needed.