Microcephaly-lymphedema-chorioretinal dysplasia: a unique genetic syndrome with variable expression and possible characteristic facial appearance.

We report on a follow-up examination of a family with microcephaly and lymphedema. The finding of chorioretinal dysplasia with variable visual deficit in multiple relatives, which was not previously discovered, supports the concept of microcephaly, lymphedema, and chorioretinopathy as being a single autosomal dominant genetic entity with variable expression. We recommend that fundoscopic examination be performed in all patients with microcephaly with or without lymphedema.

Pathologic findings in pregnancies with unexplained increases in midtrimester maternal serum human chorionic gonadotropin levels.

Second trimester maternal serum human chorionic gonadotropin (MShCG) levels are commonly obtained as part of a screening protocol for chromosomal anomalies. Approximately 4% to 6% of patients have elevated hCG levels for gestational age, and this test has been reported to identify a group at risk for pregnancy complications. We ascertained 24 patients with unexplained elevated MShCG levels and available placental pathology among 5,790 deliveries during a 58-week period and compared them with 48 controls with normal MShCG levels delivering during the same period.

Cytogenetic and molecular genetic characterization of trisomy 20 mosaicism in fetal blood and tissues.

We report a case of mosaic trisomy 20, the most common autosomal mosaicism identified in amniocytes, ascertained in a woman referred for amniocentesis because of abnormal ultrasound at 18.1 weeks' gestation which revealed short femurs and nuchal thickening. Metaphase analysis of 98 clones revealed 47,XY, +20 in 96 cells (98 per cent).

Risk-based prenatal screening for trisomy 18 using alpha-fetoprotein, unconjugated oestriol and human chorionic gonadotropin.

Nine centres collaborated to examine the feasibility of a screening method for trisomy 18 that was based on assigning individual risk, using a combination of maternal age and measurements of alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG). Second-trimester measurements of these analytes were obtained from 94 trisomy 18 pregnancies. In the 89 pregnancies without an associated open defect, the median levels for AFP, uE3, and hCG were 0.

Partial X chromosome trisomy with functional disomy of Xp due to failure of X inactivation.

A 5-month-old girl with mild phenotypic abnormalities, developmental delay, and seizures was found to have the de novo karyotype 46,XX,-13,+der(13)t(X;13)(p21.2;p11.1).

Single-operator comparison of early and mid-second-trimester amniocentesis.

We sought to determine whether early amniocentesis is a safe and acceptable method of genetic evaluation in early pregnancy. During the 54-month period from September 1986 to February 1991, 300 consecutive early second-trimester amniocenteses were performed transabdominally at 13-14 weeks' gestation and 567 consecutive mid-second-trimester transabdominal amniocenteses were performed at 16-18 weeks. Group assignment was nonrandomized, interoperator-dependent variables were eliminated, and analysis was performed in one cytogenetics laboratory.

Recombinations between IRP and cystic fibrosis.

A candidate gene for cystic fibrosis was recently isolated by selective cloning of HpaII-tiny-fragment islands; it maps considerably closer to CF than does MET or D7S8 (pJ3.11), and DNA polymorphisms from this region are in marked disequilibrium with CF. cDNA cloning has shown that this protein has a growth factor-like structure and shows homology to the murine and human proto-oncogene int-1; it is designated IRP (int-1-related protein).

Sex chromosome aneuploidy and Bardet-Biedl syndrome.

The inheritance of Bardet-Biedl syndrome is thought to be autosomal recessive. Of the approximately 500 case reports in the literature, three patients were found to have sex chromosome aneuploidy. The authors describe two siblings with Bardet-Biedl syndrome, one of whom has a unique sex chromosome aneuploidy with mosaicism, including deletion of the short arm of the X chromosome (45,X/46,X,del(X)(p21)).

A genetic association between microcephaly and lymphedema.

We discuss a family in which microcephaly and lymphedema are co-segregating as an apparently autosomal or X-linked dominant trait. A review of each malformation is presented with reference to the known genetic patterns of each. This combination of microcephaly and lymphedema may be a unique syndrome, previously undescribed because of subtleties of expression in affected individuals.

The prenatal diagnosis of the Walker-Warburg syndrome.

On the basis of physical features and autopsy findings, a child with congenital hydrocephalus, bilateral microphthalmia, myopathy, severe developmental retardation and multiple brain malformations was diagnosed to have the Walker-Warburg Syndrome (WWS). During a subsequent pregnancy in this family, a fetus at risk for this autosomal recessive condition was evaluated with serial ultrasound examinations. At 15 weeks of gestation an encephalocele was noted.

alpha-Fetoprotein: relationship between maternal serum and amniotic fluid levels.

Levels of alpha-fetoprotein were determined in 297 paired samples of maternal serum and amniotic fluid from patients with normal pregnancies at 16 to 17 completed weeks of gestation. Gestational ages were determined by menstrual history and ultrasonography, and the assays for alpha-fetoprotein were performed by a single reference laboratory. The results of the study failed to demonstrate any statistical relationship between the concentrations of alpha-fetoprotein in these two fluid compartments (r = 0.

The effects of psychosine upon growth of human skin fibroblasts from patients with globoid cell leukodystrophy.

[3H]Thymidine incorporation into cultured skin fibroblasts from patients with globoid cell leukodystrophy (GLD) and from control individuals was utilized to monitor the effects of psychosine (galactosylsphingosine) upon cell replication. The concentration of psychosine necessary to inhibit 50% (ID50) of the growth of cultured skin fibroblasts was approximately 15 microgram/ml for both normal and GLD fibroblasts deficient in the enzyme galactosylceramide beta-galactosidase. Growth inhibition curves for GLD and for control fibroblasts were comparable after 3 days and after 7 days exposure to the glycolipid, so that accumulation of psychosine was not a critical factor affecting toxicity.

Studies of a synthetic substrate in canine globoid cell leukodystrophy.

Gal et al. ((1977) Clin. Chim.