Pallister‐Killian syndrome: Review of fetal phenotype

Abstract

Pallister‐Killian syndrome is a multi‐system sporadic disorder with developmental delay. It is a rare chromosomal abnormality involving supernumerary isochormosome 12p. The disorder exhibits tissue specific mosaicism. The first prenatal diagnosis of PKS was reported in 1985 after ultrasound detection of fetal anomalies. Since this observation, there have been about 62 reports of fetuses with PKS. In this review, we cover the prenatal aspects of PKS.

Ductus Venosus Agenesis as a Marker of Pallister–Killian Syndrome

“…Pallister–Killian syndrome (PKS), also known as 12p mosaic tetrasomy, is a multisystemic disease whose prenatal diagnosis is usually an incidental finding when performing a karyotype in cases of increased nuchal translucency or fetal anomaly [10]. According to literature, the most frequent prenatal findings are polyhydramnios (37%), long bone shortening (34%), brain anomalies (20%), congenital diaphragmatic hernia (27%) fetal macrosomia (7%) cardiac malformations (16%), genitourinary malformations (10%), polydactyly and feet anomalies (19%) and gastrointestinal malformations (10%) [9].…”

“…Analyzing each of these groups, the most frequent brain malformations reported were ventriculomegaly (71%), Dandy Walker malformation (6%) and cerebellar anomalies (12%), whilst regarding cardiac malformations the most frequent ones were left ventricular hypoplasia (29%) and anomalies in aortic and pulmonary valves (28%), among others [9]. Other more sporadic anomalies are: fetal hydrops (6%), cystic hygroma (7%), increased nuchal translucency (9%) and presence of sacral appendix (3%) [9,10]. The presence of alterations in the fetal profile (small nose, thin upper lip with thick and protruding lower lip) [12] has also been related to this syndrome as well as BPD and HC measurements tending to be above the mean while fetal femur growth is under normal percentiles for gestational age [9].…”

“…PKS is an unusual genetic syndrome, with an estimated prevalence of 5.1 cases per million live births [8], and it is severe, as it usually involves serious mental retardation. Its main postnatal clinical features are moderate to severe intellectual disability/neuromotor delay, skin pigmentation abnormalities, typical facial appearance, variable association with multiple congenital malformations and epilepsy [8,9,10,11]. Though prenatal findings (including congenital diaphragmatic hernia, ventriculomegaly, congenital heart disease, polyhydramnios, and rhizomelic shortening) have been described in the literature, prenatal diagnosis is difficult as there are no distinctive or pathognomonic signs, and some of the associated malformations are hard to identify prenatally [9,10,12,13].…”

Ontogenetic and Pathogenetic Views on Somatic Chromosomal Mosaicism

“…Mosaic trisomy of chromosome 12 has been reported in nine cases with variable phenotypes [103]. Here, it is apposite to mention Pallister-Killian syndrome, which is the result of mosaic tetrasomy 12p, inasmuch as this syndrome is consistently shown to be associated with tissue-specific mosaicism (for more information, see [104,105]).…”

“…Intercellular heterogeneity is likely to be achieved by structural and behavioral variability/instability of the genome at all levels of processing genetic information (genomic, epigenomic, proteomic and metabolomic) [153,154,155]. Additionally, high rates of the instability are generated during storage and transmitting of the genetic information (i.e., DNA damage, cell cycle/mitotic checkpoint errors) [50,52,55,105]. Since chromosome number/structure changes because of cell cycle and DNA replication errors are common, SCM and CIN (genomic instability) might be an abundant source of dynamic intercellular variability of the genome in health and disease [3,52,152].…”