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.