Postnatal clinical phenotype of five patients with Pallister–Killian Syndrome (tetrasomy 12p): Interest of array CGH for diagnosis and review of the literature

Abstract

BackgroundPallister–Killian syndrome (PKS) is a rare sporadic disorder caused by tetrasomy of the short arm of chromosome 12. The main clinical manifestations are global developmental delay, intellectual disability, epilepsy, dysmorphic features, hypopigmented and/or hyperpigmented lesions, and multiple congenital anomalies. PKS is associated with tissue mosaicism, which is difficult to diagnose through peripheral blood sample by conventional cytogenetic methods and fluorescence in situ hybridization.MethodsHere, we report five patients with PKS. We delineate their clinical phenotypes and we compare them with previously published cases. We used array Comparative Genomic Hybridization (aCGH) with DNA extracted from peripheral blood samples. The five patients have also been tested by conventional cytogenetics techniques.ResultsFour out of five patients showed tetrasomy 12p by aCGH. Three of the four patients have typical i(12p) and one of the four demonstrated atypical tetrasomy 12p. The percentage of mosaicism was as low as 20%. Our cohort exhibited the typical PKS phenotypes.ConclusionOur results demonstrate the efficacy of aCGH for the diagnosis of PKS from DNA extracted from lymphocytes. Thus, for patients suspected of PKS, we recommend performing aCGH on lymphocytes at an early age before proceeding to skin biopsy. aCGH on peripheral blood samples is sensitive in detecting low level of mosaicism and it is less invasive method than skin biopsy. We reviewed also the literature concerning the previously published PKS patients diagnosed by aCGH.

Primary Amenorrhea in Pallister Killian Syndrome: Clinical Manifestation or Complication?

“…Pallister-Killian syndrome (PKS) is a rare, sporadic multisystem disorder caused by tetrasomy of the short arm of chromosome 12 presents in mosaic status. The prevalence of this condition is about 1/20.000-25.000 liveborn infants [1][2][3][4]. In some cases, PKS may be suspected before birth when second-trimester prenatal screening ultrasound reveals abnormalities or malformations such as diaphragmatic hernia or congenital heart disease [1][2][3][4].…”

“…The prevalence of this condition is about 1/20.000-25.000 liveborn infants [1][2][3][4]. In some cases, PKS may be suspected before birth when second-trimester prenatal screening ultrasound reveals abnormalities or malformations such as diaphragmatic hernia or congenital heart disease [1][2][3][4]. The phenotype of younger children with PKS is well defined [5].…”