ABSTRACT
Pallister-Killian syndrome (PKS) is a tissue limited mosaic disorder, characterized by variable degrees of neurodevelopmental delay and intellectual disability, typical craniofacial findings, skin pigmentation anomalies and multiple congenital malformations. The wide phenotypic spectrum of PKS in conjunction with the mosaic distribution of the i(12p) makes PKS an underdiagnosed disorder. Recognition of prenatal findings that should raise a suspicion of PKS is complicated by the fragmentation of data currently available in the literature and challenges in diagnosing a mosaic diagnosis on prenatal testing. Ultrasound anomalies, especially congenital diaphragmatic hernia, congenital heart defects, and rhizomelic limb shortening, have been related to PKS, but they are singularly not specific and are not present in all affected fetuses. We have combined prenatal data from 86 previously published reports and from our cohort of 114 PKS probands (retrospectively reviewed). Summarizing this data we have defined a prenatal growth profile and identified markers of perinatal outcome which collectively provide guidelines for early recognition of the distinctive prenatal profile and consideration of a diagnosis of PKS as well as for management and genetic counseling.
Subject(s)
Chromosome Disorders/diagnosis , Prenatal Diagnosis , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Chromosome Disorders/genetics , Chromosomes, Human, Pair 12/genetics , Female , Gestational Age , Humans , Phenotype , Pregnancy , Prenatal Diagnosis/methods , Retrospective Studies , Ultrasonography, PrenatalSubject(s)
Colonic Neoplasms/pathology , Lymph Nodes/pathology , Aged , Aged, 80 and over , Cell Line , Colonic Neoplasms/ultrastructure , Culture Techniques/methods , Epithelium/pathology , Epithelium/ultrastructure , Female , Humans , Karyotyping , Lymphatic Metastasis , Microscopy, Electron , Tumor Cells, CulturedABSTRACT
Silver-stained chromosomes from 29 couples with a trisomy 21 offspring and from 25 control couples were studied to determine whether there was an association of nucleolar-organizing-region variants in parents of children with trisomy 21. A reproducible scoring system for the analysis of silver-stained chromosomes was developed, and this was applied to the analysis of study participants in a blinded fashion. Seven of the 58 parents of children with trisomy 21 and seven of the 50 control parents were found to have variant NORs on silver staining. Therefore, we do not find a demonstrable risk for nondisjunction of chromosome 21 in individuals with silver-staining variants.
