Early-onset osteoarthritis due to otospondylomegaepiphyseal dysplasia in a family with a novel splicing mutation of the COL11A2 gene.
OBJECTIVE
To evaluate an approach to the clinical, radiographic, and molecular diagnosis of an underlying skeletal dysplasia in adults presenting with early-onset polyarticular osteoarthritis (OA).


METHODS
We identified a family with 2 adults with polyarticular OA and a child with generalized arthralgia. General, musculoskeletal, ocular, and auditory evaluations were undertaken. Investigations included radiographs of symptomatic joints, analysis of serum inflammatory markers and joint fluid, and mutational analyses of the COL11A2 gene.


RESULTS
The 3 affected individuals had normal stature, mild mid-face hypoplasia, and hearing impairment, but normal eyes. Radiographs of the affected adults showed severe polyarticular OA but did not reveal diagnostic evidence of an underlying skeletal dysplasia. However, the child's radiographs showed enlarged epiphyses with an advanced bone age. The combination of skeletal, facial, and auditory features together with the absence of ocular features indicated that they had otospondylomegaepiphyseal dysplasia, also known as Stickler syndrome type III. The diagnosis was confirmed by identifying a mutation in the COL11A2 gene that encodes the pre-pro-alpha2(XI) chain of type XI collagen that is involved in type II collagen fibrillogenesis.


CONCLUSIONS
Early-onset polyarticular OA may occur in adults without a known or obvious underlying skeletal dysplasia. This study provides an approach to the diagnosis of an underlying skeletal dysplasia in such individuals.
Avcin
Tadej
T
Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Makitie
Outi
O
Susic
Miki
M
Miller
Stephen
S
Thorne
Carter
C
Tenenbaum
Jerry
J
Laxer
Ronald M
RM
Cole
William G
WG
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D024161:Collagen Type XI / Q000032:analysis / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004838:Epiphyses / Q000000981:diagnostic imaging / Q000473:pathology; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010003:Osteoarthritis / Q000175:diagnosis* / Q000209:etiology*; D010009:Osteochondrodysplasias / Q000150:complications* / Q000235:genetics*; D010375:Pedigree; D011859:Radiography
C499319:COL11A2 protein, human; D024161:Collagen Type XI; D004247:DNA