Article

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. METHOD:
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. INTERPRETATION:
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.

Langue : ANGLAIS