title: Skeletal Characteristics of WNT1 Osteoporosis in Children and Young Adults.
abstract: WNT proteins comprise a 19-member glycoprotein family that act in several developmental and regenerative processes. In bone, WNT proteins regulate osteoblast differentiation and maintain bone health by activating the canonical WNT/β-catenin pathway. We reported a heterozygous missense mutation c.652T>G (p.C218G) in WNT1 exon 4 as the cause for severe early-onset, autosomal dominant osteoporosis. The initial study concerned a large Finnish family with 10 affected adults. Here we report clinical findings of the WNT1 osteoporosis in 8 children and young adults (median age 14 years; range 10 to 30 years) in two families, all with the p.C218G mutation in WNT1. Clinical assessments showed no apparent dysmorphia or features similar to typical osteogenesis imperfecta (OI). Biochemistry revealed no changes in parameters of calcium metabolism and bone turnover markers. Fracture frequencies varied, but all subjects had sustained at least one fracture and 4 had a pathological fracture history. Plain radiographs showed osteopenic appearance, loss in vertebral height, and thin diaphyses of the long bones. Bone densitometry showed the BMD to be below normal median in all subjects and the bone mass deficit seemed to be more severe in older participants. Bone histomorphometry revealed a low turnover osteoporosis in 2 subjects at ages 14 and 16 years. These findings are congruent with earlier findings in adult patients and indicate that WNT1 osteoporosis causes significant skeletal changes already in early childhood and impairs bone mass gain during pubertal years. Genetic testing of children or close relatives of affected individuals is recommended for appropriate preventive measures. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Folkhälsan Institute of Genetics and University of Helsinki, Helsinki, Finland.
authors.forename: Riikka E
authors.initials: RE
authors.lastname: Mäkitie
authors.affiliation: Department of Clinical Genetics, Turku University Hospital, Turku, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Haanpää
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Valta
authors.affiliation: Folkhälsan Institute of Genetics and University of Helsinki, Helsinki, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Pekkinen
authors.affiliation: Folkhälsan Institute of Genetics and University of Helsinki, Helsinki, Finland.|Department of Endocrinology, Institute of Medicine, Sahlgrenska University Hospital and University of Gothenburg, Gothenburg, Sweden.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Laine
authors.affiliation: Folkhälsan Institute of Genetics and University of Helsinki, Helsinki, Finland.
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.affiliation: Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Camilla
authors.initials: C
authors.lastname: Schalin-Jäntti
authors.affiliation: Folkhälsan Institute of Genetics and University of Helsinki, Helsinki, Finland.|Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Center for Molecular Medicine, Karolinska Institutet, and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015519:Bone Density; D001842:Bone and Bones / Q000473:pathology*; D002648:Child; D015331:Cohort Studies; D003720:Densitometry; D005260:Female; D006579:Heterozygote; D006801:Humans; D007866:Leg / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics; D010024:Osteoporosis / Q000097:blood / Q000235:genetics / Q000473:pathology*; D010375:Pedigree; D013131:Spine / Q000000981:diagnostic imaging / Q000473:pathology; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D051155:Wnt1 Protein
keywords: AUTOSOMAL DOMINANT OSTEOPOROSIS; BONE; COMPRESSION FRACTURE; PEDIATRIC OSTEOPOROSIS; TURNOVER; WNT SIGNALING