Genotype-phenotype correlation in 46, XY females

XY females are phenotypically females, but with XY karyotype. Our aim was to correlate the genotype with phenotype in cytogenetically confirmed 46 XY females. Retrospective study of a thirty year data Division of Human Genetics, St. John's Medical College, Bangalore, India Six hundred and twenty consecutively referred individuals with primary amenorrhea Phenotype features and XY female characteristics Fifty-seven [9.2%] cases were identified with 46, XY karyotype. Primary features: Uterus was absent in 33/47 [70.2%] cases and gonads absent in 18/34 [52.9%]. Complete female external genitalia was observed in 36/48 [75%], ambiguous genitalia with clitoromegaly in 12/57 [21.1%], normal vagina in 13/48 [27.1%], blind in 27 [56.3%] and absent in 8 [16.7%] cases. In secondary features, normal breast was seen in 23/54 [42.6%], hypoplastic in 16 [29.6%] and absent in 15 [27.8%] cases. Axillary and pubic hair was normal in 6 [11.1%] and poorly developed in 48 [88.9%]. Twelve [85.8%] were born to consanguineous parents and 8 had first cousin relationship [66.7%]. The highly significant features associated with consanguinity were normal axillary hair, ovotestis, absent vagina and significant features were hypoplastic / normal pubic hair, absent gonads and clitoromegaly. The observed differences in the percentage calculation were because of the overlapping in features as well as the available information in the records. Genotype and phenotype correlation revealed that in primary features, absence of mullerian derivatives and gonads were important whereas in secondary features, axillary and pubic hair was poorly developed

Cytogenetic studies in amenorrhea

To study the frequency of the chromosomal abnormality [CA], referred for karyotyping, and counseling in individuals with primary amenorrhea [PA] and secondary amenorrhea [SA]. We report on a retrospective survey of 865 women with amenorrhea [620-PA and 245-SA] at the Division of Human Genetics, Department of Anatomy, St. John's Medical College, Bangalore, India from 1973 to 2005. The frequency of the CA in amenorrhea was 23.35%, while PA was 26.13%, and SA was 16.33%. Numerical CA was prevalent in 45.54% of the total; 43.83% in PA, and 52.5% in SA. In numerical chromosomal abnormality, the observed karyotypes were: 45,X; 47,XXX; X mosaicism [45,X/46,XX; 45,XX/46,XX/47,XXX; 45,X/47,XXX; 46,XX/47,XXX]; Y mosaicism [45,X/46,XY; 45,X/47,XYY]; and others: 46,XX/47,XX+10; 46,XX/46,XY; 46,XX/47,XXY. In addition, is the presence of 46,XY female condition in 63 cases [31.19%], out of which 34.57% were detected to be associated with primary, and 17.5% with SA. Included in the structural chromosomal anomaly were: 46,X,i[Xq]; reciprocal translocation [46,XX,t[9;14]]; Robertsonian translocation [13;14]; X; autosomal translocations [X;12 and X;14]; deletion/duplication/ fragment/isochromosome/marker/ring formation associated either with the long or the short arms of X chromosome; 46,XX,9q-; 46,XX/46,XX,3p[break]; in a pure free status or mostly in mosaic status. The present study has emphasized that karyotyping is one of the fundamental investigations in the evaluation of amenorrhea. It has highlighted CA, one of the genetic etiology as the causal factor in amenorrhea

Genital ambiguity

Genital ambiguity [GA] is defined as a condition wherein it is difficult to assign the sex of an individual on examination of the external genital organs. A multidisciplinary approach is the corner stone in successful management. The aim of the present study was to look into the underlying genetic aetiology in the 29 consecutively referred patients with genital ambiguity to Division of Human Genetics. Seventeen have been reared as males, 9 as females and 3 of undecided sex. In the 29 patients the diagnosed conditions were: congenital adrenal hyperplasia [8]; perineoscrotal hypospadias [6]; Dubowitz and Smith-Lemli-Opitz syndrome one each; androgen insensitivity syndrome [4]; testosterone synthesis defect [1]; persistant mullerian duct syndrome [2]; 4'6,XY female [2]; 46,XX/46,XY [1]; 46,XX male [1] true hermophroditism [1]; and penile agenesis [1]. Genetic etiology revealed single gene disorders in 72.42% of cases [21] [autosomal recessive 16 [76.2%]; X-linked recessive 5 [13.8%]]; chromosomal aberrations in 4 [13.79%] [?SRY mutation in 4 6,XY female; ?SRY translocation in 46,XX male; 46,XX/46,XY mosaicism] and remaining 4 [13.79%] were considered to be sporadic. Probands and their family v