hrp0089p2-p261 | Growth & Syndromes P2 | ESPE2018

Two Different Variants of Short Stature Homeobox-Containing Gene (SHOX) Mutation in the Same Family

Graf Stefanie , Santi Maristella , Losekoot Monique , Fluck Christa E.

Objectives: Deficiency of the short stature homeobox-containing (SHOX) gene is a potential etiology of short stature in children. The phenotypic spectrum of SHOX deficiency disorders, caused by haploinsufficiency of the SHOX-gene and inherited in a pseudo-autosomal dominant manner, is highly variable, even within the same family, ranging from nonspecific short stature to Leri-Weill dyschondrosteosis (LWD). Short stature, mesomelia and Madelung deformity define the classic clin...

hrp0086p1-p611 | Growth P1 | ESPE2016

IGFALS Gene Deletion in a Family with Short Stature

Haliloglu Belma , Losekoot Monique , Kaya Avni , Wit Jan-Marteen

Background: ALS deficiency is characterized by mild short stature, delayed puberty, low serum IGF1, low serum IGFBP3 and undetectable serum ALS levels.Case: A 11.3 years old boy presented with short stature. He was born at term to consanguineous parents and the birth weight was unknown. On physical examination, his height and weight were 130.5 cm (−2.33 SDS) and 25.2 kg (−2.36 SDS) and he was prepubertal. The routine laboratory tests were nor...

hrp0084p2-403 | GH & IGF | ESPE2015

Homozygous Carriers of a Novel IGFALS Mutation are 1.5 SD Shorter than Heterozygous Relatives and Tend to have Lower Bone Mineral Density

Isik Emregul , van Doorn Jaap , Demirbilek Huseyin , Losekoot Monique , Wit Jan-Maarten

Background: There are limited data on differences in height, bone mineral density (BMD) and pubertal delay between homozygous and heterozygous carriers of IGFALS defects.Objective and hypotheses: To describe clinical and laboratory features and BMD of homozygous and heterozygous carriers of a novel IGFALS mutation in a large Kurdish family.Method: Index cases were two first degree cousins presenting with short stature, low IGF1, ve...

hrp0084p2-508 | Pituitary | ESPE2015

The IGSF1 Deficiency Syndrome: An Unusual Case

Aisenberg Javier , Ghanny Steven , Chartoff Amy , Zidell Aliza , Pedro Helio , Joustra Sjoerd , Losekoot Monique , Wit Jan

Background: IGSF1 deficiency has been recently found to be a novel cause of x-linked central hypothyroidism, macroorchidism and delayed puberty.Case presentation: We present a family, in which the proband was diagnosed with congenital central hypothyroidism by neonatal screening and treated accordingly. Further pituitary examination revealed an unmeasurable prolactin level, normal IGF1, normal cortisol and no abnormalities of the pituitary on MRI. The pa...

hrp0092p1-228 | Growth and Syndromes (to include Turner Syndrome) (1) | ESPE2019

Broadening of the Phenotypic Spectrum of Coats Plus Syndrome: A Patient Presenting with Extreme Short Stature as a Hallmark Feature

Riquelme Joel , Mericq Veronica , Pena Fernanda , Boogaard Merel W. , van Dijk Tessa , van Duyvenvoorde Hermine A. , Wit Jan-Maarten , Losekoot Monique

Background and Aims: Coats plus syndrome (MIM # 612199) is a highly pleiotropic disorder particularly affecting brain, eye, bone and gastrointestinal tract. We describe the phenotype of a patient with severe growth failure where whole exome sequencing (WES) revealed compound heterozygosity for two mutations in the CTC1 gene.Patient and Methods: The patient, the fourth child of healthy non-consanguineous parents, was born...

hrp0082p1-d2-216 | Reproduction (1) | ESPE2014

IGSF1 Variants in Boys with Familial Delayed Puberty

Joustra Sjoerd , Wehkalampi Karoliina , Oostdijk Wilma , Biermasz Nienke , Howards Sasha , Bernard Daniel , Maarten Wit Jan , Dunkel Leo , Losekoot Monique

Background: The immunoglobulin superfamily member 1 (IGSF1) gene encodes a plasma membrane glycoprotein enriched in pituitary and testes. Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism (CeH), macroorchidism, and delayed pubertal rise of testosterone despite normal timing of testicular growth. This syndrome was discovered in patients with CeH; therefore, it is presently unknown whether IGSF1 mutations also cau...

hrp0084p1-81 | Growth Hormone | ESPE2015

The Growth Response to Growth Hormone Treatment is Greater in Patients with SHOX Enhancer Deletions Compared to SHOX Defects

Donze Stephany , Meijer Caroline , Kant Sarina , Zandwijken Gladys , van der Hout Annemieke , van Spaendonk Resie , van den Ouweland Ans , Wit Jan Maarten , Losekoot Monique , Oostdijk Wilma

Background: Short stature caused by point mutations or deletions of the short stature homeobox (SHOX) gene (SHOX haploinsufficiency, SHI) is a registered indication for growth hormone (GH) treatment. Patients with a SHOX enhancer deletion (SED) have a similar phenotype, but their response to GH is unknown. It is uncertain if duplications of SHOX or its enhancer (SDUP) can cause short stature.Objective and hypotheses: To describe the clinical characterist...

hrp0086fc11.1 | Thyroid | ESPE2016

Mutations in TBL1X as a Novel Cause of Familial Central Hypothyroidism

Heinen Charlotte , Losekoot Monique , Sun Yu , Watson Peter , Fairall Louise , Joustra Sjoerd , Zwaveling-Soonawala Nitash , Oostdijk Wilma , van den Akker Erica , Santen Gijs , van Rijn Rick , Dreschler Wouter , Surovtseva Olga , Biermasz Nienke , Hennekam Raoul , Wit Jan , Schwabe John , Boelen Anita , Fliers Eric , van Trotsenburg Paul

Background: Congenital central hypothyroidism (CeH) may occur isolated, or in combination with other pituitary hormone deficiencies. Although a third causative gene for CeH was recently reported (IGSF1), the aetiology of isolated CeH has remained unexplained in most cases.Objective and hypotheses: We hypothesized that in three relatives with unexplained isolated CeH a mutation in another gene might be responsible for the phenotype.<p class="...