Background: Pseudoisodicentric X chromosomes with an Xq deletion (46,X,idic(Xq)) are rare. Most cases are mosaic, the other cell line being 45,X. Nonmosaicism is rare. Phenotype is characterized by the resultant of the X deletion. Variations from short to tall stature can occur and premature ovarian failure is a common feature.
Case presentation: A 16 year old girl was referred to our clinic with primary amenorrhoea. She was also known with learning disabilities. Physical examination showed a normal height (+0.8 SDS) and minimal pubertal development (A1, P2, M1-2). Laboratory testing demonstrated hypergonadotrophic hypogonadism: FSH 62,8 U/L; LH 19,4 U/L; estradiol <0,06 nmol/L; and progesterone <0,6 nmol/L.
Results: Conventional karyotyping of lymphocytes repeatedly revealed an aberrant X chromosome consisting of twice the short arm, twice a centromere and twice the long arm until Xq27, with a loss of a small part of the long arm of the X chromosome (nonmosaic 46,X,psu idic (X) (q27)). Genomic micro-array showed duplication of Xp22.33q27,1 and deletion of Xq27,1q28.
Conclusion: The deletion of only a small part of Xq supports the 'inactivation' hypothesis, which means that a larger deletion of the long arm of the X chromosome leads to a larger part of inactivation of that X chromosome. Consequently, the two short stature-homeobox (SHOX) genes located in the region of Xp present on the aberrant chromosome are inactivated. The exact mechanism behind this theory remains to be discovered. In our patient, the deletion of Xq is small. This small deletion did not inactivate the SHOX genes, explaining the normal stature. Xq26 q27 is critical for ovarian functioning, as reported in literature. Deletion of Xq27 in our patient caused premature ovarian failure and as a consequence hypergonadotrophic hypogonadism.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology