Czech Dysplasia

A number sign (#) is used with this entry because Czech dysplasia is caused by heterozygous mutation in the COL2A1 gene (120140) on chromosome 12q13.

Description

Czech dysplasia is an autosomal dominant skeletal dysplasia characterized by early-onset, progressive pseudorheumatoid arthritis, platyspondyly, and short third and fourth toes (Marik et al., 2004; Kozlowski et al., 2004).

Clinical Features

Williams et al. (1993) described a family living in the Chiloe Islands, Chile, in which 7 members in 3 generations had spondyloepiphyseal dysplasia with shortened metacarpals and metatarsals, precocious osteoarthritis, and periarticular apatite-like calcific deposits. The proband was a 40-year-old woman with short fourth and fifth metatarsals and intermittent acute pain and swelling in her knees, ankles, and proximal interphalangeal joints since the age of 12 years. As a result of severe degenerative joint disease, she underwent total hip replacement at age 35; this was complicated by marked heterotopic periarticular calcification. Complete physical examination, anthropometric measurements, and radiographic studies of the spine and peripheral joints in 16 family members revealed that 7 had spondyloepiphyseal dysplasia tarda, brachydactyly, precocious osteoarthritis, and periarticular calcification, while 2 others had the same syndrome without brachydactyly (Reginato et al., 1994).

Marik et al. (2004) and Kozlowski et al. (2004) described a dominantly inherited progressive pseudorheumatoid dysplasia that could be distinguished from progressive pseudorheumatoid arthropathy of childhood (PPAC; 208230), the disorder first reported by Spranger et al. (1980), by dominant inheritance and the unique phenotypic feature of hypoplasia/dysplasia of 1 or 2 toes. They reported a total of 7 patients originating from different parts of the Czech Republic. Kozlowski et al. (2004) suggested that the disorder be designated Czech dysplasia, metatarsal type.

In the family reported by Marik et al. (2004) in which 4 affected individuals were studied, weather-dependent articular pain was characteristic. This feature was absent in the patients described by Kozlowski et al. (2004). The abnormality of the toes was due to short third and fourth metatarsals. The patients were normal adult height.

As outlined by Kozlowski et al. (2004), skeletal abnormalities were located predominantly in the spine, pelvis, hips, and feet. They included mild platyspondyly with irregularity of the vertebral plates, narrowing of the joint and intervertebral disc spaces, rectangular shape of the lumbar spinal canal in the anteroposterior projection, and dysplasia of the pelvis, hips, and proximal femora.

Tzschach et al. (2008) described a large German family in which 11 members had Czech dysplasia. In addition to typical features of the disorder, all 11 had hearing loss starting in early adulthood. They noted that hearing deficits had been reported in 2 other families with Czech dysplasia (Bleasel et al., 1995; Lopponen et al., 2004) and suggested that hearing loss be added to the major features of the disorder.

Matsui et al. (2009) reported a Japanese family in which a father, daughter, and son had features consistent with Czech dysplasia, including normal height, joint pain in childhood with limited joint mobility, and short toes. The 37-year-old father had already undergone hip replacement. All 3 patients had sensorineural hearing loss. Radiography revealed platyspondyly, irregular vertebral endplates, osteoarthritis, osteochondromatosis, and short metacarpals and metatarsals. In addition, valgus knee, a feature not previously described in Czech dysplasia, was present in all 3 patients. Matsui et al. (2009) stated that this was the first report of a non-European family with Czech dysplasia.

Molecular Genetics

In affected members of a Chilean family with spondyloepiphyseal dysplasia with shortened metacarpals and metatarsals, precocious osteoarthritis, and periarticular apatite-like calcific deposits, Williams et al. (1993) identified heterozygosity for an arg75-to-cys (R75C) mutation in the COL2A1 gene (120140.0018). (The R75C mutation has also been designated R275C based on a different numbering system.)

Hoornaert et al. (2007) noted phenotypic similarities between patients with Czech dysplasia and patients with the COL2A1 R75C mutation. They performed targeted sequencing of exon 13 of the COL2A1 (120140) gene in patients with Czech dysplasia and identified heterozygosity for the R75C mutation in 2 of the 4 original patients described with Czech dysplasia (case I in Marik et al. (2004) and affected mother of case II in Kozlowski et al. (2004)). The R75C mutation was also found in 3 additional patients. All 5 affected individuals had normal height, spondyloarthropathy, and short postaxial toes. Three individuals had osteochondromatosis of the knee.

In all affected members of a large German family with Czech dysplasia, Tzschach et al. (2008) identified the R75C mutation resulting from an 823C-T transition in the COL2A1 gene.

In 3 affected individuals from a Japanese family with Czech dysplasia, Matsui et al. (2009) identified heterozygosity for the R75C mutation in the COL2A1 gene (120140.0018).