Predictive factors in recurrent spontaneous aborters--a multicenter study.

PROBLEM: Compare data from several centers relating to success rates in recurrent spontaneous miscarriage and assess the significance of indicators of subsequent pregnancy loss. METHOD: Data from 777 couples with unexplained recurrent spontaneous abortion from independent studies at seven centers were analyzed using logistic regression analysis. The following covariates were considered: age of patient, number of previous spontaneous abortions, length of previous abortions history, sub-fertility index (defined as the product of the number of spontaneous abortions and the abortion history), whether a patient was a primary or secondary aborter, and whether a patient had received leukocyte immunotherapy. RESULTS: There was a highly significant difference between the seven centers in success rates in the subsequent pregnancy and a highly significant association between success rate and each of the following covariates: the number of previous abortions, the length of the previous abortion history and the sub-fertility index. In particular, for each increase of 10 units in the value of the sub-fertility index, up to a value of 30, the odds in favor of a successful pregnancy decreased by a factor of 0.6, i.e., 40%. There was, however, little evidence of an association between the success rate in the subsequent pregnancy and age, parity, or immunization with cells from the husband. CONCLUSIONS: The sub-fertility index may be a useful measure of likelihood of success in a subsequent pregnancy.

Adult familial dyslexia: a retrospective developmental and psychosocial profile.

This study investigated the developmental, demographic, educational, and psychosocial outcome of 36 adults with third-generation familial dyslexia. Control subjects were 44 unaffected age-matched family members. Compared with control subjects, those with familial dyslexia 1) had similar incidences of perinatal complications, left-handedness, and right-left confusion but reported more early speech/language problems; 2) performed worse in reading and spelling but had similar educational achievement; 3) were more likely to report depression/anxiety symptoms and to have attention-deficit disorder with hyperactivity; and 4) were similar in medical history, marital stability, and mean income. Data suggest that, despite continued isolated reading deficits, carefully selected subjects with adult familial dyslexia do not show the previously described downward course of the learning-disabled population.

Linkage analysis of neurofibromatosis type I, using chromosome 17 DNA markers.

The gene for von Recklinghausen neurofibromatosis type 1 (NF1) has recently been mapped to the pericentromeric region of human chromosome 17. To further localize the NF1 gene, linkage analysis using chromosome 17 DNA markers was performed on 11 multigeneration families with 175 individuals, 57 of whom were affected. The markers used were D17Z1 (p17H8), D17S58 (EW301), D17S54 (EW203), D17S57 (EW206), D17S73 (EW207), CRI-L946, HOX-2, and growth hormone. Tight linkage was found between NF1 and D17Z1, D17S58, and D17S57 with a recombination fraction of zero. One recombinant was detected between NF1 and D17S73, showing linkage with a 10% recombination fraction. No linkage was detected between NF1 and CRI-L946 or between HOX-2 and growth hormone. Our data are consistent with the proposed gene order pter D17S58-D17Z1-NF1-D17S57-D17S73 qter.

Variable expressivity of neurofibromatosis-1 in identical twins.

Monozygotic twins with Neurofibromatosis-1 (NF-1) who have both concordant and discrepant clinical manifestations are reported. At 7 years of age, both twins were found to have learning disabilities, poor fine and gross motor skills, but different distributions of café-au-lait spots, axillary freckling, and iris Lisch nodules; only twin A was found to have multiple neurofibromas involving the mesentery. Manifestations of mesenteric neurofibromas have not been reported previously to occur this early in childhood; they are an unusual presenting feature of NF-1.

Linkage analysis of neurofibromatosis.

Linkage analysis of neurofibromatosis was performed using genes on chromosomes 1, 8, 11, and 12. No linkage was found between NF and C-myc, AT 3, IGF-1, PTH, and gamma globin genes. Evidence for linkage was found between C-ets 1, on the long arm of chromosome 11 and NF in two families with a lod score of 1.88 at theta = 0. More families are being studied to confirm this linkage.

X-linked Leigh's syndrome.

Two male half siblings developed rapid progression of neurologic symptoms at 11/2 and 21/2 years of age. Neither boy had a metabolic acidosis. Characteristic features of subacute necrotizing encephalomyelopathy, the neuropathologic basis of Leigh's syndrome, were demonstrated at autopsy. X-linkage of the disorder was considered because the boys had different fathers. An X-linked form of Leigh's syndrome was supported by a review of the literature, which showed an unexplained male/female ratio in Leigh's syndrome of 1.83/1, and a significant excess of male-male siblings. An X-linked form of Leigh's syndrome would explain the excess of males, and may account for some of the clinical and biochemical heterogeneity.

Late-onset X-linked recessive spinal and bulbar muscular atrophy.

A family is described in which five males have late-onset facial weakness, dysarthria, dysphagia, and slowly progressive proximal weakness. Electrodiagnostic studies and muscle biopsy were compatible with spinal muscular atrophy. This family appears quite similar to several previously reported families with late-onset X-linked recessive spinal and bulbar muscular atrophy. Because of the relative homogeneity of this particular phenotype of spinal muscular atrophy, a single metabolic derangement was sought. Three obligate carriers were studied, and no abnormality was detected. A further family with this condition is briefly discussed.

Survey of amniocentesis for fetal sex determination in hemophilia carriers.

A study was designed to determine whether there is an increased risk of complications when amniocentesis for fetal sex determination is performed on hemophilia carriers. Questionnaires were sent to 112 medical centers providing this service in the United States, and to 19 outside the United States. Responses were received from 76% of the centers in the United States. Data on 11,819 taps were obtained. Only 75 taps (0.64%) were performed for the indication of hemophilia. The frequency of fetal deaths in the general sample (1.84%) was not significantly different from that in the subsample of hemophilia carriers (1.33%). The results of this survey correspond very closely to data from a National Registry on amniocentesis for various indicaions in such variables as the number of taps needed for diagnosis, color of the fluid obtained, and number of dry taps. Carrier women who had bleeding problems during the monitored pregnancy are described. The problems might have been related to the amniocentesis in three women. It is calculated that only 2-4% of hemophilia carrier women who might have amniocentesis are utilizing the service.

Carrier detection in classical hemophilia.

Rabbit antibody to purified human factor VIII was prepared and absorbed until it formed only one precipitin line against normal and hemophilic plasmas and no line against severe von Willebrand's disease plasma. The plasma protein which combines with this rabbit antibody to factor VIII is referred to as factor VIII antigen. The ratio of percent factor VIII activity (by coagulation assay) to percent factor VIII antigen was used for carrier detection. Thirty-seven normal women, 33 obligate carriers, 12 probable carriers, and 39 possible carriers, were studied by this technique. Using the ratio of 0.84 as the division between normals and carriers, 31 of the 33 carriers (91%) were classified carriers. Twenty of the 39 possible carriers were classified as carriers (51%) and ten of the 12 probable carriers were positively identified. The results of discriminate analysis of all three variables (VIII activity, VIII antigen, and the ratio of VIII activity to VIII antigen indicated that the discrimination power of the ratio alone could not be improved by introducing the other variables on this set of data. These findings confirm the usefulness of the VIII activity to VIII antigen ratio in the detection of carriers of classical hemophilia.