50 Years Ago in The Journal of Pediatrics: Testicular Feminization and Color Blindness

Abstract

RJ Blattner. J Pediatr 1960;56:425-7A comprehensive description of the clinical manifestations of resistance to androgens was first provided in 1953 by John Morris, who coined the term “testicular feminization.” Seven years later, Blattner used the same term in the title of his comments on this disorder of sex development. In the past few years, most clinicians have abandoned the term “testicular feminization” and adopted the term “complete androgen insensitivity syndrome” (CAIS), which more accurately reflects the pathophysiology of this disorder and is less controversial and disturbing to patients and families. In his article, Blattner correctly describes the physical characteristics of a woman with CAIS (normal breast development, absent or scant pubic and axillary hair, blind-ending vagina, absent uterus and Fallopian tubes, and testes located intra-abdominally, in the inguinal canals, or in the labia majora). In addition, he recognizes that this condition is not due to a chromosomal abnormality and supports the hypothesis previously put forth by Grumbach and Barr that “testicular feminization is associated with either a sex-linked recessive gene or a sex-limited autosomal dominant gene.” Indeed, CAIS is due to deletions or (more commonly) single base substitutions in the androgen receptor gene, which is located on the long arm of the X chromosome. The phenotypes resulting from impaired androgen action depend on the severity of the androgen receptor disruption and encompass mild androgen insensitivity (normal male phenotype associated with infertility or gynecomastia), partial androgen insensitivity (various degrees of genitalia ambiguity), and CAIS. In addition, a particular androgen receptor mutation may be associated with a heterogeneous phenotypic expression, with the same mutation reported in different individuals associated with either complete or partial androgen insensitivity. Finally, another interesting aspect of this article is the description of families in which testicular feminization and color blindness were variably cosegregated in XY individuals, consistent with the notion that both were sex-linked traits. The genes encoding the red and green photopigments are located on the long arm of the X chromosome, and red-green color vision defects are in fact inherited as X-linked recessive traits. Despite the concomitant occurrence of these 2 genetic abnormalities in the families described in the article, the prevalence of CAIS is quite rare (between 1 case in 20 000 and 1 case in 100 000 genetic males), and that of red-green color vision defects is much more common (in 8% of males of European descent). RJ Blattner. J Pediatr 1960;56:425-7 A comprehensive description of the clinical manifestations of resistance to androgens was first provided in 1953 by John Morris, who coined the term “testicular feminization.” Seven years later, Blattner used the same term in the title of his comments on this disorder of sex development. In the past few years, most clinicians have abandoned the term “testicular feminization” and adopted the term “complete androgen insensitivity syndrome” (CAIS), which more accurately reflects the pathophysiology of this disorder and is less controversial and disturbing to patients and families. In his article, Blattner correctly describes the physical characteristics of a woman with CAIS (normal breast development, absent or scant pubic and axillary hair, blind-ending vagina, absent uterus and Fallopian tubes, and testes located intra-abdominally, in the inguinal canals, or in the labia majora). In addition, he recognizes that this condition is not due to a chromosomal abnormality and supports the hypothesis previously put forth by Grumbach and Barr that “testicular feminization is associated with either a sex-linked recessive gene or a sex-limited autosomal dominant gene.” Indeed, CAIS is due to deletions or (more commonly) single base substitutions in the androgen receptor gene, which is located on the long arm of the X chromosome. The phenotypes resulting from impaired androgen action depend on the severity of the androgen receptor disruption and encompass mild androgen insensitivity (normal male phenotype associated with infertility or gynecomastia), partial androgen insensitivity (various degrees of genitalia ambiguity), and CAIS. In addition, a particular androgen receptor mutation may be associated with a heterogeneous phenotypic expression, with the same mutation reported in different individuals associated with either complete or partial androgen insensitivity. Finally, another interesting aspect of this article is the description of families in which testicular feminization and color blindness were variably cosegregated in XY individuals, consistent with the notion that both were sex-linked traits. The genes encoding the red and green photopigments are located on the long arm of the X chromosome, and red-green color vision defects are in fact inherited as X-linked recessive traits. Despite the concomitant occurrence of these 2 genetic abnormalities in the families described in the article, the prevalence of CAIS is quite rare (between 1 case in 20 000 and 1 case in 100 000 genetic males), and that of red-green color vision defects is much more common (in 8% of males of European descent).