Aplasia of the Müllerian system: evidence for probable sex-limited autosomal dominant inheritance.

Thirteen unrelated females ranging in age from 15 to 28 years old have recently been recognized to have aplasia of the müllerian duct derivatives. They presented one or both of two major complaints: amenorrhea and difficulty or pain on attempted sexual intercourse. Clinically all cases were characterized by absence of vagina and failure to palpate the uterus rectally; normal mature external genitalia; normal stature, intellect, hearing and vision; normal secondary sex characteristics including breast development, pubic and axillary hair. Libido was normally preserved and sexual self-identification was unambiguously feminine. Apart from the pelvic findings, the affected individuals were phenotypically unremarkable women. Laparoscopic examination revealed absent uteri, absent or rudimentary tubes, but normally developed ovaries. Cytogenetic evaluation disclosed normal female karyotypes with normal banding patterns on all patients. Endocrine investigations revealed female cyclic pattern consistent with normal ovarian endocrine function. Biopsy specimens on the ovaries of 5 patients were histologically unremarkable with evidence of normal follicular activity. Investigation of the families of these patients revealed similarly affected individuals in 10 families. In 8 of these the pattern of transmission was consistent with autosomal dominant inheritance with sex limitation to XX individuals; in 2 the distribution of affected individuals was compatible with either sex-limited autosomal dominant or autosomal recessive inheritance. Though unlikely, polygenic inheritance remains a formal possibility. In 3 families, apart from the propositae, no other affected females were ascertained. In these, the etiology is either teratogenic or genetic with autosomal dominant or recessive inheritance, and sex limitation to females. Three further cases with partial aplasia or the Rokitansky-Kuster-Hauser syndrome (RKHS) were ascertained. No other similarly affected individuals were encountered in their families.