No abstract

Currently, accepted protocol which has been developed at the Prenatal Diagnosis Laboratory of New York City (PDL) requires that when a chromosome abnormality is found in one or more cells in one flask, another 20-40 cells must be examined from one or two additional flasks. Chromosome mosaicism is diagnosed only when an identical abnormality is detected in cells from two or more flasks. In a recent PDL series of 12,000 cases studied according to this protocol, we diagnosed 801 cases (6.68 per cent) of single-cell pseudomosaicism (SCPM), 126 cases (1.05 per cent) of multiple-cell pseudomosaicism (MCPM), and 24 cases (0.2 per cent) of true mosaicism. Pseudomosaicism (PM) involving a structural abnormality was a frequent finding (2/3 of SCPM and 3/5 of MCPM), with an unbalanced structural abnormality in 55 per cent of SCPM and 24 per cent of MCPM. We also reviewed all true mosaic cases (a total of 50) diagnosed in the first 22,000 PDL cases. Of these 50 cases, 23 were sex chromosome mosaics and 27 had autosomal mosaicism; 48 cases had numerical abnormalities and two had structural abnormalities. Twenty-five cases of mosaicism were diagnosed in the first 20 cells from two flasks, i.e., without additional work-up, whereas the other 25 cases required extensive work-up to establish a diagnosis (12 needed additional cell counts from the initial two culture flasks; 13 required harvesting a third flask for cell analysis). Our data plus review of other available data led us to conclude that rigorous efforts to diagnose true mosaicism have little impact in many instances, and therefore are not cost-effective. On the basis of all available data, a work-up for potential mosaicism involving a sex chromosome aneuploidy or structural abnormality should have less priority than a work-up for a common viable autosomal trisomy. We recommend revised guidelines for dealing with (1) a numerical versus a structural abnormality and (2) an autosomal versus a sex chromosome numerical aneuploidy. Emphasis should be placed on autosomes known to be associated with phenotypic abnormalities. These new guidelines, which cover both flask and in situ methods, should result in more effective prenatal cytogenetic diagnosis and reduced patient anxiety.

Asymptomatic hyperechoic foci were noted within the left cardiac ventricular chamber on the prenatal sonograms of 26 patients between 16 and 20 weeks of gestation. Their range of occurrence, the prenatal follow-up in 12 patients and postnatal echocardiograms in six patients, indicate a clinically insignificant congenital anomaly associated with the chordae tendinae.

We report on 7 patients with the Silver-Russell syndrome (SRS) in two 3-generation families. Three patients in each of the families had an undergrowth of the left side of the body when compared with the normal right side. The clinical courses were mild as compared to the severity sometimes described in sporadic cases. These patients and a review of 190 SRS cases from the literature showed that there were 23 families in which 38 patients had completely expressed SRS. In 17 of the families, multiple maternal relatives had complete or partial expressions of the SRS. Most SRS patients have been reported to occur sporadically; however, of the 197 propositi analyzed, 19% had more than one affected individual in a family and several different modes of inheritance could have been responsible. Two families (8.7%) had spontaneous dominant mutations (twins) and possible autosomal recessive transmission was present in 4 families (17.4%). Because no male-to-male transmission has yet been documented in the 21 families in the literature and the two families reported here, X-linked dominant inheritance is a possibility in 17 families (74%). Thus, although sporadic occurrences and genetic heterogeneity appear to be involved in the SRS, dominant inheritance may be a major causal factor.