title: Multiple epiphyseal dysplasia.
abstract: BACKGROUND
  Multiple epiphyseal dysplasia (MED) is a common genetically and clinically heterogeneous skeletal dysplasia characterized by early-onset osteoarthritis, mainly in the hip and knee, and mild-to-moderate short stature. Here we report on a 6-generation MED family with 17 affected members.
  
  
  METHODS
  The clinical and radiographic data on the 12 affected members still living were scrutinized. A structured inquiry comprising state of health and MED-related symptoms since birth up to the present time and the osteoarthritis outcome (KOOS) questionnaire were sent to all living family members with MED. The 5 known gene loci for autosomal dominant MED were analyzed for linkage, using fluorescence-labeled microsatellite markers. Linkage was ascertained with markers close to the COL9A2 gene, which was analyzed for mutations by sequencing.
  
  
  RESULTS
  We identified an exon 3 donor splice mutation in the COL9A2 gene in all affected family members. Clinical, radiographic, and questionnaire data from affected family members suggested that MED caused by COL9A2 mutations starts in early childhood with knee pain accompanied by delayed ossification of femoral epiphyses. The disease then either stabilizes during puberty or progresses with additional joints becoming affected; joint surgery might be necessary. The progression of the disease also affects muscles, with increasing atrophy, resulting in muscle fatigue and pain. Muscular atrophy has not been reported earlier in cases with COL9A2 mutations.
  
  
  CONCLUSIONS
  In a patient with clinically suspected or verified MED, it is important to perform DNA-based analysis to identify a possible disease-causing mutation. This information can be used to carry out genetic risk assessment of other family members and to achieve an early and correct diagnosis in the children.
authors.affiliation: Department of Genetics and Pathology, the Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Dahlqvist
authors.forename: Hanna
authors.initials: H
authors.lastname: Orlén
authors.forename: Hans
authors.initials: H
authors.lastname: Matsson
authors.forename: Niklas
authors.initials: N
authors.lastname: Dahl
authors.forename: Torsten
authors.initials: T
authors.lastname: Lönnerholm
authors.forename: Karl-Henrik
authors.initials: KH
authors.lastname: Gustavson
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D024081:Collagen Type IX / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D011859:Radiography; D011795:Surveys and Questionnaires; D013548:Sweden; D055815:Young Adult
chemical_list: C120282:COL9A2 protein, human; D024081:Collagen Type IX