title: PTEN hamartoma tumor syndrome and Gorham-Stout phenomenon.
abstract: PTEN: hamartoma tumor syndrome (PHTS) is a group of syndromes caused by mutations in PTEN. Gorham-Stout phenomenon (GSP) is a rare condition characterized by proliferation of vascular structures in bones, resulting in progressive osteolysis. Here we present a 1-year-old boy with PHTS and GSP. The lesion that later proved to be GSP was evident from the age of 4 months, and became symptomatic at the age of 1 year. Eventually, he developed a fatal chylothorax. Mutation analysis revealed a germline heterozygous mutation c.517 C>T (p.Arg173Cys) in exon 6 of PTEN. Analysis of the lymphatic malformation (LM) tissue revealed no loss of heterozygosity (LOH) nor a second, somatic PTEN mutation of the remaining wild type allele. The germline p.Arg173Cys mutation was also present in the mother and the propositus' younger sister and brother. Further molecular work-up showed a heterozygous variant c.2180C>T (p.Ala727Val) FLT4 in the LM tissue, which was also present in the germline of mother and two siblings. GSP has not been reported before in a patient with a PTEN mutation. Up to this date, this mutation is the only genetic defect possibly involved in the etiology of GSP which is plausible given the known function of PTEN in angiogenic signaling.
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Saskia M J
authors.initials: SM
authors.lastname: Hopman
authors.forename: Rick R
authors.initials: RR
authors.lastname: Van Rijn
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: Johannes
authors.initials: J
authors.lastname: Bras
authors.forename: Marielle
authors.initials: M
authors.lastname: Alders
authors.forename: Chantal M
authors.initials: CM
authors.lastname: van der Horst
authors.forename: Raoul C M
authors.initials: RC
authors.lastname: Hennekam
authors.forename: Johannes H M
authors.initials: JH
authors.lastname: Merks
mesh_terms: D005190:Family; D017809:Fatal Outcome; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000175:diagnosis* / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D010015:Osteolysis, Essential / Q000175:diagnosis* / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human