Determining a prenatal profile for Pallister-Killian Syndrome leads to earlier genetic counseling and symptom management.
Pallister-Killian syndrome (PKS) is a genetic condition which results in a variety of symptoms, including facial dysmorphisms, skin discolorations, intellectual disability, developmental delay, congenital heart defects, congenital diaphragmatic hernia (abdominal hernias that occur in fetuses), malformations in the gastrointestinal tract and urinary tract, shortened limbs, and hearing loss. PKS is caused by an additional isochromosome 12p. Typically, a chromosome has a short arm (termed the “p arm”) and a long arm(termed the “q arm”) joined at the middle (the centromere). An isochromosome 12p occurs when chromosome 12 has two p arms, instead of a p and a q. So, the patients have 4 copies of the genes of the short arm of chromosome 12 instead of two. Usually additional isochromosome 12p is found only in some cells whereas other cells may have a normal karyotype.
Prenatal diagnosis is difficult for PKS, and often relies on detection of symptoms (for example, presence of a diaphragmatic hernia) in order to be noticed. Therefore, tools and resources are necessary in order to diagnose PKS more effectively at the prenatal level. This article hopes to help solve this issue by comparing 114 cases of PKS (mostly from the published literature) in order to better characterize the disease prenatally.
In reviewing the data, the most common prenatal findings in PKS patients included polyhydramnios(excessive amniotic fluid in the uterus) and long bone shortening – both of which can be detected by the 17th week of gestation. Fetuses with PKS also typically display fetal macrosomia – they are significantly larger than average. In the second trimester of pregnancy, common prenatal features include ventriculomegaly (ventricles in the brain are enlarged), cardiac septal defects, and calico-pelvic dilatation (widening of the renal pelvis of the kidney).
In terms of prenatal screens, nuchal translucency (NT) might aid as an initial screen for PKS. NT refers to the fluid filled space between the fetal skin and the overlying skin, and enlarged NT usually corresponds with unfavorable prenatal outcomes. In the PKS patients, enlarged NT was often associated with more severe symptoms, such as cardiac heart defects. Though each of these observations is not enough information for a concrete diagnosis of PKS, collectively they can help in detecting the disease at an earlier stage than before.
Producing a proper prenatal diagnosis of PKS can lead to earlier genetic counseling and management of symptoms. If symptoms of PKS are detected, then an amniocentesis can be performed in an attempt to detect the 12p isochromosome specifically.
The article concludes by reiterating the current prenatal profile of PKS: polyhydramnios, long bone shortening, macrosomia, ventriculomegaly, cardiac septal defects, calico-pelvic dilatation, and high NT measurement. More research needs to be conducted to elucidate more prenatal findings; primarily, the distinct facial characteristics of PKS that may be revealed through 3D ultrasound evaluations.
Salzano, et al. “Prenatal profile of Pallister-Killian syndrome: Retrospective analysis of 114 pregnancies, literature review and approach to prenatal diagnosis”. American Journal of Medical Genetics 2018, v. 176 (12), 2575-2586.
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