Clinical characteristics and analysis of misdiagnosing mixed gonadal dysgenesis

Objective To explore the clinical characteristics and causes and countermeasures of misdiagnosing mixed gonadal dysgenesis (MGD). Methods From May 2013 to April 2018, clinical data were retrospectively reviewed for 24 MGD children. The average age was 21(10-39) months and the average height 83(71-97) cm. Ten children fell below the average height of the same age group by 2 standard deviations. There were 22 boys and 2 girls. The Prader grade was II (n=3), III (n=15) and IV (n=6). The results of sex hormone determination and sex-related genes were analyzed.Fluorescence in situ hybridization (FISH) for sex chromosome was further tested in 8/10 children with 46, XY chromosome. And gonad specimens were evaluated for histopathology. Results The average level of anti-mullerian hormone (AMH) was 69.42(16.57-189.92) ng/ml. The average testosterone level was 4.93(0.71-8.09) nmol/L after hCG stimulation. WT1 gene mutation was detected in 1 child with a definite diagnosis of Danis-Drash syndrome (DDS). The karyotypes were 45, X/46, XY, 10 cases of 46, XY (n=12, including 8 cases confirmed by FISH as X chimeric XY), 45, X/46, XY/47XYY (n=1) and 45, X/47, XYY/48XYYY (n=1). Forty-eight specimens were classified as dyspastic testis (n=24), undifferentiated gonad tissue (n=1) (previously misdiagnosed as ovary tissue) and fibrous stripe gonads with sex-cord-like structure (n=4). No evidence of malignancy was noticed. Conclusions Ambiguous genitalia is common in MGD children with Muller tube remnant. For suspected MGD children with a 46, XY chromosome, further FISH test for sex chromosome is warranted. And undifferentiated gonad tissue may be found in a streak gonad and ovary tissue is probably mistaken for making a misdiagnosis of ovotesticular DSD. Key words: Gonadal dysgenesis; Sex chromosomes; Histopathology