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We report a case of multiple endocrine neoplasia type 2A (MEN 2A) diagnosed prenatally at 16 weeks gestation. The 35-year-old mother is a MEN 2A patient. She had had three prior pregnancies: one resulted in a stillbirth; one produced a genetically unaffected boy; and the third was terminated in the first trimester owing to a diagnosis of blighted ovum. Autopsy did not reveal the cause of death of the stillborn infant, who was also found to be affected with MEN 2A by molecular study of paraffin-embedded tissue. Because of poor obstetric history and the patient's age, amniocentesis for cytogenetic and molecular studies was performed at 16 weeks' gestation during the pregnancy under discussion. As with other affected members in the mother's family, the missense mutation of TGC to TTC at codon 634 of the RET proto-oncogene was found in amniotic fluid cells. Analysis of DNA extracted from the lymphocytes of the infant's blood at birth confirmed the diagnosis. To our knowledge, this is the first report of prenatal diagnosis of MEN 2A.

The polymerase chain reaction was used to test 18 adults and eight fetuses with numerical or structural X-chromosome abnormalities for the presence of nine Y-specific loci. Y-chromosomal DNA was detectable in one adult patient with X-chromosome mosaicism. This study and previous reports provide evidence to support further screening of patients with X-chromosome abnormalities for the presence of Y-chromosomal DNA sequences. Long-term follow-up of patients with Y-chromosomal sequences is required to determine the risk of gonadal neoplasms and other abnormal phenotypes.

Patients with clinical features of Turner's syndrome may have a 45,X/46,X + mar or 46,X + mar karyotype. It is estimated that phenotypic females or intersexuals with a Y chromosome and gonadal dysgenesis have a 20% risk of developing gonadoblastoma, so it is crucial to know whether Turner's syndrome patients have a Y chromosome. We studied the chromosomal make-up of four patients with Turner's syndrome using the polymerase chain reaction (PCR). Nine Y-chromosomal loci including four loci (PABY, SRY, ZFY, DYS14) on the short arm, one loci (DYZ3) on the centromere, and four loci (DYS132, DYS1, DYZ1, DYZ2) on the long arm were amplified to determine the origin of marker chromosomes. Three patients were identified as having Y chromosome DNA. Patient 1 contained the presumed gonadoblastoma locus (DYS132) and a prophylactic gonadectomy was carried out. DNA extracted from dysgenetic gonads did not show Y chromosome DNA. A rapid, highly sensitive and isotope-free method for detection of abnormal Y chromosomes in Turner's syndrome patients has been developed. Chromosome in situ hybridization analysis is required to confirm the PCR results, to provide further evidence for molecular organization of these marker chromosomes.

Alpha-thalassemia is the most common single gene disorder in Taiwan and Southeast China. The majority of alpha-thalassemic mutations in this area are alpha-thalassemia 1. Homozygous alpha-thalassemia 1 has been recognized as the most important cause of hydrops fetalis. To investigate the incidence of alpha-thalassemia 1 mutations and to characterize its molecular defects, cord blood electrophoresis was performed on 2,000 newborns, of which 99 (5%) cases were found to have hemoglobin (Hb) Bart's levels > 3.0%. A methodology using biphasic polymerase chain reaction (PCR) with nesting primers was developed to characterize the alpha-thalassemia 1 Southeast Asia type (SEA) deletion in the cases with detectable Hb Bart's levels. The SEA deletion was found in 92 (93%) of 99 cases. Prenatal screening was performed on couples with abnormal hematologic indices, and PCR was used to detect couples heterozygous for SEA deletion. Prenatal diagnosis was performed in 21 cases, and four cases were found to have a homozygous SEA deletion. This strategy can be applied to couples who need prenatal genetic counseling for alpha-thalassemia major in this area.

X chromosome mosaicism is usually associated with abnormal sexual development and reproductive performance, such as recurrent spontaneous abortion, primary or secondary amenorrhea, infertility, and premature ovarian failure. However, there is a paucity of literature which discusses these relationships. From July 1988 to December 1992, a total of 105 couples with a history of recurrent spontaneous abortion from a genetic counseling clinic and 61 women with a history of premature ovarian failure followed up in reproductive endocrinology clinics were assembled, and chromosomal analysis of peripheral blood lymphocytes was carried out. X chromosome mosaicism was found in six individuals (2.9%) out of the 105 couples with recurrent spontaneous abortion, and in five (8.2%) out of 61 women with premature ovarian failure. The karyotypes were 45,X/46,XX/47,XXX in five cases, 45,X/46,X in four cases, and 46,XX/47,XXX in two cases. The cases of complex X chromosome mosaicism (45,X/46,XX/47,XXX) presented recurrent spontaneous abortion in four cases and premature ovarian failure in one case. The cases of mosaic Turner's syndrome (45,X/46,XX) presented premature ovarian failure in three cases and recurrent spontaneous abortion in one case. The two cases of mosaic triple-X syndrome (46,XX/47,XXX) presented with premature ovarian failure and recurrent spontaneous abortion, respectively. However, the ratio of mosaic cell lines does not correlate well with the phenotypic manifestations in our cases. Our preliminary data suggest that chromosomal analysis should be done routinely in every couple with recurrent spontaneous abortion and in women with premature ovarian failure. The reproductive performance of X chromosome mosaicism is highly variable and difficult to define.(ABSTRACT TRUNCATED AT 250 WORDS)

Two cases of dicentric isochromosome X, dic (Xp-), with premature ovarian failure are presented. The karyotype of case 1 is 46,X,dic(X)(qter-->p22::p22-->qter), and of case 2 is 45,X (77.5%)/46,X,dic(X)(qter-->p22::p22-->qter) (22.5%). An abnormal menstrual history including delayed menarche and secondary amenorrhea occurring at under 30 years of age was noted. Hormonal profiles revealed elevated levels of serum gonadotropins and decreased levels of estrogens. Gross appearance did not present an obvious picture of Turner's syndrome, except for short stature, poor development of secondary sexual characteristics and infertility. The possible mechanisms of dicentric isochromosome X are the breakage and reunion between either sister chromatid (isodicentric) or homologous chromosomes (homodicentric) which occur during meiosis of the germ cells in case 1 and mitosis after zygote formation in case 2.

A less bulky uterine myoma is technically easier to deal with during surgery. Recently gonadotropin-releasing hormone agonists (GnRH-a) have been used for the purpose of medical hypophysectomy, thereby reducing the size of uterine myomas. Ten premenopausal women with infertility and intramural-submucous myoma manifesting with menorrhagia and obstruction of the tubal ostia were recruited for this study. A long-acting depot GnRH-a, Decapeptyl, was given intramuscularly every four weeks for three months as an adjunct prior to myomectomy. Luteinizing hormone, follicular stimulating hormone and estradiol declined to the menopausal range following treatment. The size of the myoma decreased to a mean of 32.3 +/- 13.3% of the original volume. Myomectomy was performed in eight patients at the end of the study. Remarkably little blood loss was observed during the surgery. All of the patients had their uteri preserved, and six out of eight patients achieved pregnancy within 12 months after surgery. Our results indicate that monthly administration of long-acting GnRH-a significantly reduces the myoma volume and makes myomectomy technically easier to perform with the possibility of reduced complication rates and better preservation of future fertility.

Pelvic actinomycosis with multiple fistular formation is rarely reported in the literature. We herein present a case of pelvic actinomycosis with sigmoid colo-ileovesical fistulae in a 36-year-old intrauterine device (IUD) user. She was admitted to the hospital because of general malaise, weight loss and bilateral palpable adnexal masses. Sonography showed bilateral adnexal masses which contained many echolucent spots. A barium enema examination revealed sigmoid colo-ileo-vesical fistulae. A computed tomographic scan showed bilateral cystic adnexal masses, bilateral hydronephrosis and hydroureter. Preoperatively, pelvic malignancy was suspected. An exploratory laparotomy was performed. Bilateral tubo-ovarian abscesses with extensive adhesions were found. Pathologic examination of the operative specimen revealed pelvic actinomycosis. The patient was treated with penicillin for 14 weeks and had a stable clinical course.