The X chromosome contains 155 million pairs of bases (pb) and over 1000 genes 16 while the Y chromosome has a length of 60 million pb and contains over 200 genes, from which only 48 are codifiers. 17 Inactivation of the X chromosome in women allows for an equilibrium in gene doses with respect to men; however, the so-called pseudoautosomic regions (PAR1 and PAR2) escape X chromosome inactivation and their genes are counterparts to those within PAR1 and PAR2 of the Y chromosome. Additionally, only in said regions is there a meiotic recombination among X and Y chromosomes.
The Turner’s syndrome phenotype can be explained by a haploinsufficiency of the genes which are normally expressed in both sexual chromosomes and which escape X inactivation
6 Mb of the short arm of X and Y human chromosomes. 18,19 It contains at least 24 genes, all of which escape X inactivation. 6 The PAR2 region is in the distal end of the long arm, and is much smaller since it only covers 320 kb 7 . It presents a lower recombination frequency and is composed of pseudogenes, for the most part. Four genes have been identified in this region ( HSPRY3 , VAMP7 , IL9R and CXYorf1 ) located in a telomeric center direction.
The SHOX gene (short-stature homebox) located in Xp (PAR1) belongs to the homebox gene family, which is a transcriptional regulator and key controller of multiple processes during embryonic development. Location of the SHOX expression during embryogenesis is correlated to many phenotypic features of Turner’s syndrome, since it intervenes in the development of the elbow and knee, its haploinsufficiency is associated with skeletal alterations such as cubitus valgum, genu valgum and Madelung deformity. Its expression in the first and second pharyngeal arches takes part in the formation of the upper and lower maxillary, ears and external hearing meatus, 20 hence its link to a narrow palate and retrognathia. Short size is explained by the SHOX haploinsufficiency, which acts as a transcription factor over the B-type natriuretic peptide (BNP), expressed mainly in cardiac tissue and better known by its vasodilator properties. However, BNP is also expressed in other tissues, including cartilage, where it is necessary for normal chondrogenesis. 21 Other genes located in the short arm of the X chromosome may contribute to the variability observed in the delay in growth. As mentioned above, BPN’s predominant expression in cardiac tissue and its transcriptional control by the SHOX gene may explain cardiac alterations in these patients.
Although there are no genetic findings which explain visceral and soft tissue affectation, some phenotypical data such as lymphedema, pterigium colli and cardiac abnormalities have been linked with lymphatic hypoplasia attributable to other genes which escape X chromosome inactivation and are located in the Xp region. Immunohistochemical studies conducted in fetuses with TS showed a decrease in the expression of endothelial and vascular growth factor ( FLT4 , PTN63 , LYVE1 , Prox1) receptors, a decrease that may be linked to abnormal lymphatic genesis. 22,23
The PAR1 region covers 2
Since structural alterations of the heart and vascular system are much more common in girls with cystic hygroma or lymphedema, it has been suggested that abnormal lymph nodes are involved in the development of these heart diseases. Moreover, it has been speculated that aortic coarctation is the result of abnormal lymphatic flow, which is characteristic of TS. On the other hand, there is the hypothesis that myocardial hypoplasia is a primary defect caused by lymphedema; since over 90% of fetuses with TS course with hydrops, the heart weighs under the 2.5th percentile (in relation to the weight of other organs and gestational age) while an altered heart weight was less common in those fetuses with hydrops of other etiologies. 24