Pallister-Killian syndrome (PKS) is a multi-system developmental disorder caused by tetrasomy 12p that exhibits tissue-limited mosaicism. Probands with PKS often demonstrate a unique growth profile consisting of macrosomia at birth with deceleration of growth postnatally. We have previously demonstrated that cultured skin fibroblasts from PKS probands have significantly elevated expression of insulin-like growth factor binding protein-2 (IGFBP2). To further evaluate the role of IGFBP2 in PKS, the amount of IGFBP2 secreted from cultured skin fibroblast cell lines and serum IGFBP2 levels were measured in probands with PKS. Approximately 60% of PKS fibroblast cell lines secreted higher levels of IGFBP2 compared to control fibroblasts, although the remaining 40% of PKS samples produced comparable level of IGFBP2 to that of control fibroblasts. Serum IGFBP2 levels were also measured in PKS probands and were elevated in 40% of PKS probands. PKS probands with elevated IGFBP2 manifested with severe postnatal growth retardation. IGFBPs are the family of related proteins that bind IGFs with high affinity and are typically thought to attenuate IGF action. We suggest that elevated IGFBP2 levels might play a role in the growth retardation phenotype of PKS.
Keywords: growth retardation; isochromosome 12p; mosaicism.
© 2015 Wiley Periodicals, Inc.