(Small amounts of a fetuss DNA escapes through the placenta to circulate in the mothers blood.) A genome-wide association study done in China used genome-wide cfDNA analyses to diagnose various chromosome-related disorders including PKS. The study scanned the DNA in the blood of 29,007 pregnant women and found three cases with abnormal amount of DNA originating from the entire p-arm of chromosome 12. All three cases were confirmed to have a fetus with PKS. Two of these cases were missed by chromosomal microarray analysis of the placenta and chorionic villi. However, the study did not define the rate of false negative cases, i.e. negative results in women actually carrying a fetus with PKS. While further studies are required, this method may turn out to be a critically useful addition for the prenatal detection of PKS, particularly during early pregnancies for the purpose of pregnancy options counseling. Postnatal diagnosis
The postnatal diagnosis of PKS is strongly suggested or indicated in most cases based on finding the key defects of PKS in an individual on physical examination and various radiography, ultrasound, and related methods. However, some individuals with this syndrome do not have a sufficient number of these defects or have a set of defects that are also compatible with other birth defect disorders such as Fryns syndrome, trisomy 12p, and Sifrim-Hitz-Weiss syndrome (also termed CHD4 Neurodevelopmental Disorder). The diagnosis can be confirmed in these cases as well as in all cases of PKS by detecting its sSMC using special methods.
Recent studies in two individuals with PKS found their sSMCs consisted specifically of genetic material located in a stretch of chromosome 12 s p arm starting at its band 11 and running to its end. This area, called the PKS critical region, contains three genes, ING4, CHD4, and MFAP5 (also termed the MAGP2 gene), which are candidates for contributing to the development of the syndrome.One suggested mechanism for the development of the sSMC in PKS involves three sequential events: 1) chromosome 12 suffers a nondisjunction, i.e. a failure of its homologous chromosomes or sister chromatids to separate properly during the second meiosis cell division that forms maternal eggs; 2) while most of the eggs with this nondisjunction die, a rare egg with the nondisjunction acquires a second structural aberration, isochromosome formation, that results in the creation of an extra chromosome consisting of copies of two or four p arms but no q arms of chromosome 12, i.e. the sSMC; and 3) the sSMC-containing egg, after being fertilized by a genetically normal sperm, develops into an offspring containing copies of this sSMC in some but not all cells, tissues, and/or organs consequently have some but not all of the defects associated with PKS. This mechanism applies only to female parents who are by far the most common originators of the sSMC in PKS. The mechanism explaining the few cases in which male parents form a sperm containing this sSMC has not yet been clearly formulated.