| OBJECTIVE: To analyze the clinical features,gonadal characteristics and molecular genetic characteristics of children with mixed gonadal dysgenesis,and to discuss the relationship between the clinical phenotypic characteristics of this type of children and their molecular genetic characteristics in order to improve the understanding and diagnosis of this disease.METHODS: A retrospective analysis is performed to correlate the clinical manifestations,gonadal levels,imaging,gonadal phenotypes and gonadal pathological features with the molecular biological characteristics of 12 children with mixed gonadal dysgenesis(karyotype 45,X/46,XY chimerism or its variants)seen at Chengdu Women’s and Children’s Center Hospital between January 2010 and January 2023.The correlations are summarized and analyzed.RESULTS:(1)A total of 12 patients with mixed gonadal dysgenesis are included in the study,of which 10 patients are diagnosed by G-banding method,2 patients are diagnosed by further refinement of FISH test,and 2 of 12 patients are positive for SRY gene.(2)Ten of the 12 patients are female by gender and two are male by gender.The patients included in the study had a wide range of external genitalia phenotypes,from completely male phenotype,gender ambiguous,and completely female phenotype.12 patients are further classified into female phenotype(8 cases),external genitalia gender ambiguous(2 cases),and male phenotype(2 cases)according to external genitalia masculinization score and Prader’s classification.The EMS scores of the female patients are between 0 and 4,and the Prader score is between Prader 0 and grade 3.The EMS scores of the male patients are between 11 and 12,and the Prader score is between grade 5 and Prader 6.(3)By physical examination and imaging,neither ovaries nor testes are seen in the 2 patients with gender ambiguity;the gonads are testes in 2patients with male phenotype(2/2);bilateral ovarian-like gonads are seen in 1 patient with female phenotype(1/8),testicular-like gonads are seen in 1 patient(1/8),and no exact gonadal tissue is seen in 6 patients(6/8);7 patients has further abdominal exploratory surgery,2 patients did not find any gonadal tissue during the surgery.Pathology in all patients with ambiguous genital gender shows unilateral striae contralateral to the testis(2/2),and pathology in 3 of the 5 patients with female phenotype suggests bilateral striae like gonads(3/5),1 suggests absence of one side contralateral to the ovary(1/5),and in 1 case bilateral gonadal absence was seen during surgery(1/5);gonadoblastoma is detected in postoperative pathology in 2 of the 7patients operated on(28.57%).(4)The age distribution of the patients with mixed gonadal dysgenesis in the study ranged from 0.84 to 16 years old,and the main reasons for initial diagnosis are sexual developmental abnormalities and/or short stature(5patients with sexual developmental abnormalities,6 patients with short stature,and 1patient with both).(5)All patients in the study has varying degrees of short stature,with a mean height standard deviation of-2.22 SD for the female phenotype and-1.89 SD for the male phenotype;half of the patients has multiple types of Turner syndrome signs.Hypergonadotropic hypogonadism are present in all patients.CONCLUSION: The EMS score is a systematic method for scoring the external genitalia and gonads,but most of patients had short stature and some patients had Turner syndrome-like signs.The clinical phenotype of patients with mixed gonadal dysgenesis did not correlate significantly with the percentage of chromosome chimerism in peripheral blood.Patients with mixed gonadal dysgenesis are at high risk for gonadoblastoma,with a higher incidence in the female phenotype than in the male phenotype.Early abdominal exploration and gonadal biopsy are recommended in all patients with mixed gonadal dysplasia to assess gonadal development and to exclude the risk of tumor. |
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