Spondyloepimetaphyseal Dysplasia, Strudwick Type

A number sign (#) is used with this entry because of evidence that the Strudwick type of spondyloepimetaphyseal dysplasia is caused by heterozygous mutation in the type II collagen gene (COL2A1; 120140) on chromosome 12q13.

Description

The Strudwick type of spondyloepimetaphyseal dysplasia (SEMD) is characterized by disproportionate short stature, pectus carinatum, and scoliosis, as well as dappled metaphyses (summary by Tiller et al., 1995).

Clinical Features

The features of the Strudwick type of SEMD include severe dwarfism, superficially resembling the Morquio syndrome, and pectus carinatum and scoliosis which are usually marked. Cleft palate and retinal detachment are frequently associated, as in spondyloepiphyseal dysplasia congenita (SEDC; 183900). A distinctive radiographic feature is irregular sclerotic changes, described as 'dappled' in the metaphyses of the long bones. This mottled appearance is created by alternating zones of osteosclerosis and osteopenia. The eponym Strudwick is derived from a prototype patient at the Johns Hopkins Hospital who was born with midface hemangioma, cleft palate, inguinal hernia, and clubfoot; his mental development was normal (Murdoch and Walker, 1969) (Anderson et al., 1982).

Anderson et al. (1982) presented the clinical and radiographic findings in 8 patients, radiographs on an additional 6 patients, and morphologic observations on chondroosseous tissue from 2 of the 14 patients. Disproportionately short limbs and delayed epiphyseal maturation are present at birth. Radiologically the disorder is indistinguishable from SED congenita during infancy. Distinctive metaphyseal changes ('dappling'), which allow identification of the entity, develop during early childhood. The dappling is greater in the ulna than in the radius and greater in the fibula than in the tibia. Severe scoliosis and cord compression are important problems of early adulthood. Anderson et al. (1982) suggested that the cases reported by Kozlowski and Budzinska (1966) and Diamond (1974) may represent the same disorder.

Spranger and Maroteaux (1982) were dubious about the distinctness of the syndrome from SED congenita. Kousseff and Nichols (1984) defended the diagnosis of Strudwick SMED in patients 5 and 6 in the report of Anderson et al. (1982). The children were judged to be of average intelligence; earlier, mental retardation was thought to be present and to distinguish their disorder from Strudwick dysplasia. Urinary tract anomalies were present in one of them.

Sulko et al. (2005) described monozygotic twin girls with a phenotype resembling SEDC but with more severe shortening of stature than in SEDC and normal craniofacies. In addition, the twin girls had deformed chest, shortening of the extremities with the upper arms and the legs most severely affected, brachydactyly, and genu varum. Distinctive radiographic features included oval-shaped vertebral bodies with an anterior tongue-like protrusion, widened, irregular metaphyses, an irregular trabecular pattern at the end of the shaft of the tubular bones, and C1/C2 subluxation. The most severely affected metaphyses were the proximal femoral, distal tibial, and proximal humeral. Radiologic analysis of the short tubular bones showed that apart from shortening they were within normal limits.

Inheritance

Anderson et al. (1982) observed affected brother and sister with normal unrelated parents of Puerto Rican ancestry, and favored autosomal recessive inheritance. Tiller et al. (1995) later showed that Strudwick SEMD is inherited as an autosomal dominant trait.

Molecular Genetics

In 3 patients with SEMD Strudwick type, Tiller et al. (1993, 1995) found that cartilage contained both normal alpha-1(II) collagen chains and chains that were posttranslationally overmodified. By sequence analysis, they demonstrated heterozygosity for 3 different mutations in the COL2A1 gene (120140.0017, 120140.0027, and 120140.0028, respectively), thus establishing dominant inheritance.

By sequencing of the COL2A1 gene in monozygotic twin girls with SEMD Strudwick, Sulko et al. (2005) identified heterozygosity for a missense mutation (120140.0047).

History

Maumenee and Cranley (1975) observed a seemingly novel type of spondylometaphyseal dysplasia in a brother and sister and their father. Involvement of the cervical and thoracic spine and hips was particularly severe. Abnormal storage of glycogen was demonstrated in cartilage cells of the iliac crest growth plate by histochemical methods and electron microscopy. Pettersson and Nilsson (1979) gave the designation spondylometaepiphyseal dysplasia to a disorder they observed in mother and daughter. Kozlowski et al. (1982) attempted a classification of this nosologically difficult category.