Turner's syndrome was originally described as a disorder ofadultwomen characterized byinfantilism, congenital webbed neck, and cubitus valgus (Turner, I938). It was later shown that the important pathological defect was the absence of normal ovaries which are invariably replaced by thin white 'streaks' of ovarian stroma without follicles (Wilkins and Fleischmann, I944). With the accumulation of clinical experience, the criteria for inclusion in the syndrome have become modified and enlarged, so that Turner's syndrome can now be defined more accurately as a disorder of women in which short stature, infantilism, streak gonads, and associated congenital malformations are the four cardinal features. The associated malformations are so characteristic that it is useful to refer to them as 'Turner stigmata'. They include shield chest, webbing of the neck, peripheral lymphoedema at birth, short IVth metacarpals, hypoplastic nails, multiple pigmented naevi, and coarctation of the aorta (Haddad and Wilkins, i959). A number of patients have been observed who have many features in common with Turner's syndrome, but who do not qualify for the complete syndrome on these criteria because they lack one or more of the cardinal features. Thus, some patients are of normal stature, some have secondary amenorrhoea, some are without Turner stignnata, and some show masculinization. These patients may be referred to as variants ofTurner's syndrome. In 1954 it was shown that many patients with Turner's syndrome have chromatin-negative nuclear sex (Polani, Hunter, and Lennox, I954), and five years later the explanation of this anomaly was provided by the demonstration of an XO sex chromosome constitution in a typical patient (Ford, Jones, Polani, de Almeida, and Briggs, I959). However,

https://jmg.bmj.com/content/jmedgenet/2/2/142.full.pdf

Karyotype-phenotype correlations in gonadal dysgenesis and their bearing on the pathogenesis of malformations.

The age of occurrence of gonadal tumors in intersex patients with a Y chromosome.

Over 600 cases with a Y aneuploidy (other than non-mosaic 47,XYY) were reviewed for phenotype/karyotype correlations. Except for 93 prenatally diagnosed cases of mosaicism 45,X/46,XY (79 cases), 45,X/47,XYY (8 cases), and 45,X/46,XY/47,XYY (6 cases), all other cases were ascertained postnatally. Special emphasis was placed on structural abnormalities. This review includes 11 cases of 46,XYp-; 90 cases of 46,XYq- (52 cases non-mosaic; 38 cases 45,X mosaic); 34 cases of 46,X,r(Y) (9 cases non-mosaic and 25 cases 45,X mosaic); 8 cases of 46,X,i(Yp) (4 non-mosaic and 4 mosaic with 45,X); 12 cases of 46,X,i(Yq) (7 non-mosaic and 5 mosaic); 44 cases of 46,X,idic(Yq); 80 cases of 46,X, idic(Yp) (74 cases had breakpoints at Yq11 and 6 cases had breakpoints at Yq12); 130 cases of Y/autosome translocations (50 cases with a Y/A reciprocal translocation, 20 cases of Y/A translocation in 45,X males, 60 cases of Y/DP or Y/Gp translocations); 52 cases of Y/X translocations [47 cases with der(X); 4 cases with der(Y), and 1 case with 45,X with a der(X)], 7 cases of Y/Y translocations; 151 postnatally diagnosed cases of 45,X/46,XY; 14 postnatally diagnosed cases of 45,X/47,XYY; 18 cases of 45,X/46,XY/47,XYY; and 93 aforementioned prenatally diagnosed cases with a 45,X cell line. It is clear that in the absence of a 45,X cell line, the presence of an entire Yp or a region of it including SRY would lead to a male phenotype in an individual with a Y aneuploidy, whereas the lack of Yp invariably leads to a female phenotype with typical or atypical Ullrich-Turner syndrome (UTS). Once there is a 45,X cell line, regardless of whether there is Yp, Yq, or both Yp and Yq, or even a free Y chromosome in other cell line, there is an increased chance for that individual to be a phenotypic female with UTS manifestations or to have ambiguous external genitalia. This review once again shows a major difference in reported phenotypes between postnatally and prenatally diagnosed cases of 45,X/46,XY, 45,X/47,XYY, and 45,X/46,XY/47,XYY mosaicism. It appears that ascertainment bias can explain the fact that all known patients with postnatal diagnosis are phenotypically abnormal, while over 90% of prenatally diagnosed cases are reported to have a normal male phenotype. Further elucidation of major Y genes and their clinical significance can be expected in the rapidly expanding gene mapping projects. More, consequently better, phenotype/karyotype correlations can be anticipated at both the cytogenetic and the molecular level.

Phenotype/Karyotype correlations of Y chromosome aneuploidy with emphasis on structural aberrations in postnatally diagnosed cases

It is widely accepted that male determination in man depends on the presence of a factor or factors on the Y chromosome. These factors may be localised within the Y chromosome through the study of structural anomalies of the Y. A thorough review of seven different structural anomalies of the Y is presented: dicentric Y chromosomes, Y isochromosomes, ring Y chromosomes, Y; autosome, Y;X, and Y;Y translocations, and Y deletions. The evidence from these studies indicates that a gene or genes on the short arm or the Y near the centromere play a crucial role in the development of the testes. A few studies indicate that one or more factors on the long arm of the Y may also influence testicular development. If such a factor is present on the long arm, then it too must be very near the centromere. The theory that separate genes independently control the initial development and maturation of the tests (on the long and short arms of the Y, respectively) may be premature. Recently proposed arguments in its favour are examined. Some evidence also indicates the presence of a fertility factor on the non-fluorescent segment of the long arm. Relevant information on the H-Y antigen is discussed.

https://jmg.bmj.com/content/jmedgenet/18/3/161.full.pdf

Localisation of male determining factors in man: a thorough review of structural anomalies of the Y chromosome.

Phenotypic features and functions known to depend on the presence of the Y chromosome or the H-Y antigen are discussed in relation to structural anomalies of the Y chromosome and other abnormalities of sexual and somatic development.

D.W. Thompson

Papers

A probable partial deletion of the Y chromosome in an intersex patient.