In a Genomic Era, Placental Pathology Still Holds the Key in the Nondysmorphic Stillbirth.

Objective To explore the relative utility of genetic testing in contrast to placental pathology in explaining causation of death in the structurally normal stillborn population. Methods A retrospective review of a structurally normal stillborn infant cohort in South East Scotland between 2011 and 2015, defined by death at or after 24 weeks of gestation. We reviewed pathology reports and collected demographic data on cases. This information was collated with genetic test results (quantitative fluorescent polymerase chain reaction and microarray analysis) and placental pathology to create a database for analysis. Primary Results Within the structurally normal population (n = 131), there were 125 genetic tests performed and 11 abnormal results. Sixty-six microarray analyses were performed, and 2 (3%) of the results were thought likely to reflect cause of stillbirth (1 case of incomplete trisomy 4 and 1 case of deletion of chromosome Xp in a female). Analysis was significantly limited in 2 cases as parental samples were not available. The placental pathology was available in a total of 129 cases; significant findings were identified in 100 cases; 79 (61%) showed changes that were considered to have caused death (including cord "accidents"), and a further 21 (16%) showed findings likely to influence the management of subsequent pregnancies. Conclusions We reaffirm the utility of placental examination in the investigation of stillbirth. In cases of nondysmorphic stillbirth where placental pathology does not explain the cause of stillbirth, microarray analysis of fetal DNA can add further diagnostic information in 3% of cases but can add further diagnostic confusion, and it is important that parental bloods are taken to minimize this risk.

Transmitted duplication of 8p23.1-8p23.2 associated with speech delay, autism and learning difficulties.

Duplications of distal 8p with and without significant clinical phenotypes have been reported and are often associated with an unusual degree of structural complexity. Here, we present a duplication of 8p23.1-8p23.2 ascertained in a child with speech delay and a diagnosis of ICD-10 autism. The same duplication was found in his mother who had epilepsy and learning problems. A combination of cytogenetic, FISH, microsatellite, MLPA and oaCGH analysis was used to show that the duplication extended over a minimum of 6.8 Mb between 3 539 893 and 10 323 426 bp. This interval contains 32 novel and 41 known genes, of which only microcephalin (MCPH1) is a plausible candidate gene for autism at present. The distal breakpoint of the duplicated region interrupts the CSMD1 gene in 8p23.2 and the medial breakpoint lies between the MSRA and RP1L1 genes in 8p23.1.An interchromosomal insertion between a normal and polymorphically inverted chromosome 8 is proposed to explain the origin of this duplication. Further mapped imbalances of distal 8p are needed to determine whether the autistic component of the phenotype in this family results from the cumulative imbalance of many genes or dosage imbalance of an individual susceptibility gene.