title: Schimke immunoosseous dysplasia: defining skeletal features.
abstract: Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive multisystem disorder characterized by prominent spondyloepiphyseal dysplasia, T cell deficiency, and focal segmental glomerulosclerosis. Biallelic mutations in swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD, but approximately half of patients referred for molecular studies do not have detectable mutations in SMARCAL1. We hypothesized that skeletal features distinguish between those with or without SMARCAL1 mutations. Therefore, we analyzed the skeletal radiographs of 22 patients with and 11 without detectable SMARCAL1 mutations. We found that patients with SMARCAL1 mutations have a spondyloepiphyseal dysplasia (SED) essentially limited to the spine, pelvis, capital femoral epiphyses, and possibly the sella turcica, whereas the hands and other long bones are basically normal. Additionally, we found that several of the adolescent and young adult patients developed osteoporosis and coxarthrosis. Of the 11 patients without detectable SMARCAL1 mutations, seven had a SED indistinguishable from patients with SMARCAL1 mutations. We conclude therefore that SED is a feature of patients with SMARCAL1 mutations and that skeletal features do not distinguish who of those with SED have SMARCAL1 mutations.
authors.affiliation: Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kshamta B
authors.initials: KB
authors.lastname: Hunter
authors.forename: Thomas
authors.initials: T
authors.lastname: Lücke
authors.forename: Jürgen
authors.initials: J
authors.lastname: Spranger
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Smithson
authors.forename: Harika
authors.initials: H
authors.lastname: Alpay
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: André
authors.forename: Yumi
authors.initials: Y
authors.lastname: Asakura
authors.forename: Radovan
authors.initials: R
authors.lastname: Bogdanovic
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.forename: Robyn
authors.initials: R
authors.lastname: Cairns
authors.forename: Karlien
authors.initials: K
authors.lastname: Cransberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Fründ
authors.forename: Helen
authors.initials: H
authors.lastname: Fryssira
authors.forename: David
authors.initials: D
authors.lastname: Goodman
authors.forename: Knut
authors.initials: K
authors.lastname: Helmke
authors.forename: Barbara
authors.initials: B
authors.lastname: Hinkelmann
authors.forename: Guiliana
authors.initials: G
authors.lastname: Lama
authors.forename: Petra
authors.initials: P
authors.lastname: Lamfers
authors.forename: Chantal
authors.initials: C
authors.lastname: Loirat
authors.forename: Silvia
authors.initials: S
authors.lastname: Majore
authors.forename: Christy
authors.initials: C
authors.lastname: Mayfield
authors.forename: Bertram F
authors.initials: BF
authors.lastname: Pontz
authors.forename: Cristina
authors.initials: C
authors.lastname: Rusu
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Saraiva
authors.forename: Beate
authors.initials: B
authors.lastname: Schmidt
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shoemaker
authors.forename: Sabine
authors.initials: S
authors.lastname: Sigaudy
authors.forename: Natasa
authors.initials: N
authors.lastname: Stajic
authors.forename: Doris
authors.initials: D
authors.lastname: Taha
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Boerkoel
mesh_terms: D000293:Adolescent; D000328:Adult; D001842:Bone and Bones / Q000000981:diagnostic imaging*; D002648:Child; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics*; D003937:Diagnosis, Differential; D018740:Genetic Heterogeneity; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics; D006801:Humans; D008231:Lymphopenia / Q000235:genetics; D009154:Mutation; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging* / Q000235:genetics*; D010641:Phenotype; D011859:Radiography; D013577:Syndrome
chemical_list: C412482:SMARCAL1 protein, human; D004265:DNA Helicases