Pallister‐Killian syndrome: difficulties of prenatal diagnosis

Abstract

The first prenatal diagnosis of Pallister-Killian syndrome (PKS) was reported by Gilgenkrantz et al. in1985. Since this report, about 60 prenatal cases have been reported but both sonographic and cytogenetic diagnoses remain difficult. Although ultrasound anomalies such as congenital diaphragmatic hernia, polyhydramnios and rhizomelic micromelia in association with fetal overgrowth are very suggestive of the syndrome, they are inconstant and they may even be absent. The mosaic distribution of the supernumerary isochromosome 12p greatly increases these difficulties. No prenatal cytogenetic technique is sensitive enough to ensure prenatal diagnosis and false-negative results have been described on fetal blood, chorionic villi and amniocentesis. We report here two prenatal cases of PKS which illustrate the great variability of the fetal phenotype. In reviewing the 63 reported cases, we attempt to determine ultrasound indicators of the syndrome and to define a cytogenetic strategy. In cases where ultrasound indicators are present, our proposal is first to perform chorionic villus or placental sampling and then amniocentesis when the first cytogenetic result is normal. Fetal blood sampling is the least indicated method because of the low frequency of the isochromosome in lymphocytes. In this cytogenetic strategy, fluorescent in situ hybridization (FISH) and especially interphase FISH on non-cultured cells increases the probability or identifying the isochromosome. A misdiagnosis remains possible when ultrasound is not contributory; the identification of new discriminating ultrasound indicators would be very helpful in this context.

Prenatal Diagnosis of Pallister-Killian Syndrome Associated with Pulmonary Stenosis and Right Ventricular Dilatation

“…Maternal age has been considered to be a risk factor of PKS [15]. Advanced maternal age and ultrasound abnormalities are the most common indications for prenatal investigation in reports of PKS, including the present case [7].…”

“…To date, there have been approximately 70 reported cases of prenatally-diagnosed PKS, of which only 7 cases had cardiac defects [3,4,7,[16][17][18][19]. All the cases with cardiac defects, including the present case, are detailed in Table 1.…”

“…Fetal growth restriction was another distinct finding from the typical PKS in which fetal macrosomia is common [7]. Notably, pulmonary stenosis and right ventricular dilatation have never been documented in the setting of PKS.…”

“…PKS, tetrasomy of the short arm of chromosome 12, shows various forms of tissue-specific mosaicism, but the variation of isochromosome 12p is not correlated with the severity of congenital abnormalities [7,9]. Maternal age has been considered to be a risk factor of PKS [15].…”

“…Pallister-Killian Syndrome 367 vum septum pellicidum, absent visualization of the stomach, and presence of a sacral appendix [6,7]. Less severely affected individuals may present in postnatal life with mental retardation, epilepsy, skin pigmentation, and facial anomalies, including sparse anterior scalp hair, a flat occiput, hypertelorism, a short nose, a flat nasal bridge, and a short neck [8,9].…”