Disorders of Sex Development by John M. Hutson Garry L. Warne & Sonia R. Grover

Author:John M. Hutson, Garry L. Warne & Sonia R. Grover
Language: eng
Format: epub
Publisher: Springer Berlin Heidelberg, Berlin, Heidelberg

16.4.3 Mixed Sex Chromosome (Aneuploidy) DSD: Mixed Gonadal Dysgenesis

Mixed gonadal dysgenesis (MGD) refers to asymmetrical gonad development, with a developed gonad on one side and a dysgenic or streak gonad on the other. It is commonly associated with a mosaic karyotype and sex chromosome aneuploidy. The karyotype is usually 45,X/46,XY. Children with 45,X/46,XY mosaicism show considerable phenotypic variation, from normal male, through all degrees of ambiguity to unvirilised female. Some have features of Turner syndrome and most have short stature (Telvi et al. 1999). It should be noted that most individuals with a 45,X/46,XY mosaicism do not have MGD; the male phenotype was found in 95% of antenatally diagnosed cases, 27% of whom had histological evidence of gonadal dysgenesis (Chang et al. 1990). A uterus and fallopian tubes can be present regardless of the gonadal sex and external genitalia. Gonadal dysgenesis manifests ­asymmetrically but both testes may have some degree of dysgenesis with raised serum FSH levels at puberty, even though during childhood one gonad appeared normal.

Children with MGD are diagnosed in various ways – by antenatal screening of pregnancies, on clinical grounds in neonates with ambiguous genitalia, at investigation of delayed puberty or short stature or when a child presents with a germ cell cancer. Examination findings may include only one palpable gonad, likely to be a testis; presence of a uterus and a testis strongly suggests MGD. The diagnosis is made with a karyotype examination, imaging and direct visualisation of the internal genitalia laparoscopically, and subsequent histological examination of the gonads (see Chap. 8).

The sex of rearing is usually concordant with the predominant external sexual phenotype, but can be difficult to assign in children who have truly ambiguous genitalia. The recommendation of the specialist team should be discussed thoroughly with the family and an informed decision made. The surgeon will then discuss the plan for genital surgery with the family.

Children with MGD are at high risk of germ cell malignancy in all gonads left in situ. The precursor of malignancy in streak gonads is gonadoblastoma, found in approximately 25% of Y-positive streak gonads (Hughes et al. 2006) whereas in testes with differentiated tubules, cancer develops from carcinoma in situ (Skakkebaek 1994). It is, therefore, recommended that gonads be removed in infancy in all children with MGD who are to be reared as girls, and any highly undifferentiated or streak gonads should be removed in those raised as boys. The consideration to leave testes in situ in a male child, when the evidence indicates a high risk of malignancy, should be made in consultation with the family. They need to be both well-informed and cognisant of the necessity for regular surveillance to prevent death from malignancy. They also need to understand that a retained dysgenic testis may also develop failure of Leydig and Sertoli cell function with time (Wikstrom and Dunkel 2008). Any retained testis should be one that is well-differentiated and should be brought into the scrotum to where it can easily be palpated every 6 months and examined by ultrasonography each year.

Download

Copyright Disclaimer:
This site does not store any files on its server. We only index and link to content provided by other sites. Please contact the content providers to delete copyright contents if any and email us, we'll remove relevant links or contents immediately.