INTRODUCTION
46, XX male syndrome is a rare disorder of sex development(DSD) characterized by a female karyotype in conformity with a male phenotype(1), which had been reported in 1964 firstly(2). The prevalence of diagnosed 46, XX male syndrome was approximately 4 per 100 000 newborn males(3, 4). 46, XX males exist three different clinical categories with typical XX males, genital ambiguities, and real hermaphrodites. It had reported 46, XX male syndrome with chronic autoimmune thyroiditis(5), and with myelodysplastic syndrome converted to acute megakaryocyte leukemia(6). We herein report a case of sex-determining region Y(SRY)-negative 46, XX male syndrome co-existing with bone marrow failure in a child with a typical male phenotype.
Whole exome sequencing (WES) reveals SRY and SRY-box family genes was negative in this patient. Gene variants were detected by WES, which associated with the loss-of-function in the female pathway, testis development, and some steroid receptor genes of sex differentiation These variants could affect gonad development with a typical male phenotype.
Case presentation
In 2017 May, an 8-year-old male referred to hospital with pancytopenia and epistaxis. Bone marrow smears indicated reduced bone marrow hyperplasia. Bone marrow biopsy showed hypoplastic hematopoietic without megakaryocytes. Paroxysmal nocturnal hemoglobinuria clone was negative. His diagnosis considered as aplastic anemia in the local hospital. He had taken dexamethasone, stanozolol, and ciclosporin. The response to the treatment is well, whereas platelet count was 23-59×109/L.
In June 2018, he admitted to our department with a complaint of platelet count dropped to 10×109/L with epistaxis intermittently. He had skin ecchymosis without splenomegaly and hepatomegaly. The male was born by a G3P2A1 mother who had premature delivery by cesarean section for abdominal pain by trauma. The cause of abortion was unknown, and his sister is healthy. Birth weight is 2.4kg. His body weight and height were 31kg and 135cm, respectively. Physical examination showed small head, small eye crack, right thumb evagination, bipedal walking inside eight-character, without milk coffee spot. Soft and normal testis were palpated.
Color doppler ultrasonography showed a normal male reproductive system. Testosterone concentration was in normal ranges. Virus detection and rheumatism inspection were negative. Repeated bone marrow smears showed hypoplastic of marrow. Trephine biopsy indicated hyperplasia of marrow diminished severely and lack of hemocyte without signs of marrow fibrosis. Bone marrow and peripheral blood culture revealed 46 chromosomes with XX constitution. Gene mutations, fusion genes, fluorescence in situ hybridization, and comet assay were no definite positive result.