title: Short Stature in Isodicentric Y Chromosome and Three Copies of the SHOX Gene: Clinical Report and Review of Literature.
abstract: Short stature homeobox gene (SHOX) mutations and pseudoautosomal region 1 (PAR1) deletions encompassing SHOX are known causes of Léri-Weill dyschondrosteosis and isolated short stature, while 3 copies of SHOX in cases with triple sex chromosome constitution are responsible for tall stature. Duplications involving SHOX have been rarely reported, and they were found in individuals with short, normal and tall stature. An adopted boy with short stature, isodicentric Y chromosome and 3 copies of SHOX is described. Normal growth hormone (GH) secretion and insulin-like growth factor 1 (IGF1) increase during an IGF1 generation test were found, ruling out impaired GH-IGF1 axis. No other organic or psychiatric causes of impaired growth were found. GH treatment improved linear growth, as reported in children with SHOX haploinsufficiency. This new report and the review of literature support that SHOX duplication may cause short stature, especially in those children with duplications of the 5'SHOX regulatory elements. Chromosome analysis and detailed molecular characterization of the duplicated region should be warranted in individuals with SHOX duplications in order to investigate the presence of occult chromosome imbalance. Additional reports and follow-up till adult height are needed to give conclusions on long-term efficacy and safety of GH treatment in short children with SHOX duplication.
authors.affiliation: Division of Cytogenetic and Molecular Biology, Azienda Ospedaliero-Universitaria Pisana (AOUP), Pisa, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Valetto
authors.affiliation: Division of Cytogenetic and Molecular Biology, Azienda Ospedaliero-Universitaria Pisana (AOUP), Pisa, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Bertini
authors.affiliation: Division of Cytogenetic and Molecular Biology, Azienda Ospedaliero-Universitaria Pisana (AOUP), Pisa, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Michelucci
authors.affiliation: Division of Cytogenetic and Molecular Biology, Azienda Ospedaliero-Universitaria Pisana (AOUP), Pisa, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Toschi
authors.affiliation: Division of Pediatrics, San Giuseppe Hospital, ASL 11, Empoli, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dati
authors.affiliation: Adolescent Medicine, Pediatric Division, Department of Obstetrics, Gynecology and Pediatrics, Azienda Ospedaliero-Universitaria Pisana (AOUP), Pisa, Italy.
authors.forename: Giampietro I
authors.initials: GI
authors.lastname: Baroncelli
authors.affiliation: Adolescent Medicine, Pediatric Division, Department of Obstetrics, Gynecology and Pediatrics, Azienda Ospedaliero-Universitaria Pisana (AOUP), Pisa, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Bertelloni
keywords: GH-IGF1 axis; SHOX; SHOX duplications; Short stature; Y chromosome rearrangement