title: Autosomal dominant brachyolmia in a large Swedish family: phenotypic spectrum and natural course.
abstract: Autosomal dominant brachyolmia (Type 3, OMIM #113500) belongs to a group of skeletal dysplasias caused by mutations in the transient receptor potential cation channel, subfamily V, member 4 (TRPV4) gene, encoding a Ca++-permeable, non-selective cation channel. The disorder is characterized by disproportionate short stature with short trunk, scoliosis and platyspondyly. The phenotypic variability and long-term natural course remain inadequately characterized. The purpose of this study was to describe a large Swedish family with brachyolmia type 3 due to a heterozygous TRPV4 mutation c.1847G>A (p.R616Q) in 11 individuals. The mutation has previously been detected in another family with autosomal dominant brachyolmia [Rock et al., 2008]. Review of hospital records and patient assessments indicated that clinical symptoms of brachyolmia became evident by school age with chronic pain in the spine and hips; radiographic changes were evident earlier. Growth was not affected during early childhood but deteriorated with age in some patients due to increasing spinal involvement. Affected individuals had a wide range of subjective symptoms with chronic pain in the extremities and the spine, and paresthesias. Our findings indicate that autosomal dominant brachyolmia may be associated with significant long-term morbidity, as seen in this family.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Giedre
authors.initials: G
authors.lastname: Grigelioniene
authors.forename: Stefan
authors.initials: S
authors.lastname: Geiberger
authors.forename: Eva
authors.initials: E
authors.lastname: Horemuzova
authors.forename: Eva
authors.initials: E
authors.lastname: Moström
authors.forename: Nina
authors.initials: N
authors.lastname: Jäntti
authors.forename: Lo
authors.initials: L
authors.lastname: Neumeyer
authors.forename: Eva
authors.initials: E
authors.lastname: Åström
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: Ann
authors.initials: A
authors.lastname: Nordgren
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
mesh_terms: D000328:Adult; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011859:Radiography; D013131:Spine / Q000000981:diagnostic imaging / Q000473:pathology; D050916:TRPV Cation Channels / Q000235:genetics*
chemical_list: D050916:TRPV Cation Channels; C416986:TRPV4 protein, human
keywords: TRPV4; autosomal dominant brachyolmia; brachydactyly; brachyolmia type 3; chronic pain; overfaced pedicles; paresthesias; platyspondyly; scoliosis; short spine