SIMPSON-GOLABI-BEHMEL syndrome type 1: How placental immunohistochemistry can rapidly Predict the diagnosis. (August 2022)

• Record Type: Journal Article
• Authors: Fiandrino, Giacomo; Arossa, Alessia; Ghirardello, Stefano; Kalantari, Silvia; Rossi, Chiara; Bonasoni, Maria Paola; Cesari, Stefania; Rizzuti, Tommaso; Giorgio, Elisa; Bassanese, Francesco; Scatigno, Annachiara Licia; Meroni, Anna; Melito, Chiara; Feltri, Monica; Longo, Stefania; Figar, Tiziana Angelica; Andorno, Annalisa; Gelli, Maria Carolina; Bertozzi, Mirko; Spinillo, Arsenio; Riccipetitoni, Giovanna; Valente, Enza Maria; Paulli, Marco; Sirchia, Fabio
• Is Part Of: Placenta. Volume 126(2022)
• Page Start: 119
• Page End: 124
• Publication Date: 2022-08
• Subjects: Simpson-Golabi-Behmel syndrome -- Glypican-3 -- GPC3 -- Placental immunohistochemistry -- Overgrowth syndromes -- Placentomegaly; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2022.06.011
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: Glypican-3 (GPC3) is an oncofetal protein involved in cellular signaling, strongly expressed in the placenta, absent or diminished in postnatal life, but often increased in human malignancies. Germline loss-of-function variants of GPC3 gene are associated with Simpson-Golabi-Behmel syndrome type 1 (SGBS1), a rare recessive X-linked overgrowth disease characterized by typical facial features, congenital abnormalities, and an increased risk of developing childhood cancers. Methods: A clinical suspicion of SGBS1 was postulated for a newborn with prenatal history of overgrowth and polyhydramnios, presenting with neonatal weight and length >99th percentile, coarse facies, iris and retinal coloboma, supernumerary nipples, and splenomegaly. While waiting for whole-genome sequencing (WGS) results, we investigated placental GPC3 immunohistochemical expression in the proband, in three additional cases of SGBS1, and disorders commonly associated with fetal macrosomia and/or placentomegaly. Results: WGS in the proband identified a likely pathogenic maternally inherited missense variant in GPC3 : c.1645A > G, (p.Ile549Val), and GPC3 immunohistochemistry demonstrated full-thickness loss of stain of the placental parenchyma. The same pattern ("null") was also present in the placentas of three additional cases of SGBS1, but not in those of unaffected controls. Discussion: Immunohistochemical expression of GPC3 in the placenta is highly reproducible. Our findings showed that a "null pattern" of staining is predictive of SGBS1 and represents a valuable aid in the differential diagnosis of fetal macrosomias, allowing targeted genetic testing and earlier diagnosis. Graphical abstract: Image 1 Highlights: Placental GPC3 immunohistochemistry for Simpson-Golabi-Behmel syndrome type 1. Placentas from 4 cases and 55 controls analysed. Loss of GPC3 expression in the villous trophoblast of affected patients. First-time evidence of genetic disease prediction by placental immunohistochemistry.