Irregular distribution of chondrocytes, enlarged chondrocyte lacunae, excessive fibrous matrix, perilacunar loss of glycosaminoglycan, excessive collagen aggregation
Rock et al. (2008) provided an overview of the brachyolmias, a heterogeneous group of skeletal dysplasias that affect primarily the spine. Type 1 brachyolmia includes the Hobaek and Toledo (271630) forms and is inherited in an autosomal recessive ... Rock et al. (2008) provided an overview of the brachyolmias, a heterogeneous group of skeletal dysplasias that affect primarily the spine. Type 1 brachyolmia includes the Hobaek and Toledo (271630) forms and is inherited in an autosomal recessive fashion. Both forms of type 1 are characterized by scoliosis, platyspondyly with rectangular and elongated vertebral bodies, overfaced pedicles, and irregular, narrow intervertebral spaces. The Toledo form is distinguished by the presence of corneal opacities and precocious calcification of the costal cartilage. Type 2 brachyolmia (613678), sometimes referred to as the Maroteaux type, is also an autosomal recessive disorder, primarily distinguished from type 1 by rounded vertebral bodies and less overfaced pedicles. Some cases are associated with precocious calcification of the falx cerebri. Type 3 brachyolmia (113500) is an autosomal dominant form, caused by mutation in the TRPV4 gene (605427), with severe kyphoscoliosis and flattened, irregular cervical vertebrae. Paradoxically, although the limbs are mildly shortened in all types of brachyolmia, they show minimal epiphyseal and metaphyseal abnormalities on radiographs. Type 4 brachyolmia (612847) is an autosomal recessive form, caused by mutation in the PAPSS2 gene (603005), with mild epiphyseal and metaphyseal changes.
Brachyolmia comes from the Greek for 'short trunk.' Occasional patients have been described with short stature limited to the trunk and with radiologic changes likewise only in the spine (reviews by Fontaine et al., 1975, and Shohat et ... Brachyolmia comes from the Greek for 'short trunk.' Occasional patients have been described with short stature limited to the trunk and with radiologic changes likewise only in the spine (reviews by Fontaine et al., 1975, and Shohat et al., 1989). Hobaek (1961) included probable cases in his series; some of these were instances of multiple affected sibs and consanguineous parents. Kozlowski et al. (1982) stated that pure brachyolmia does not exist and that metaphyseal involvement may be minimal and scattered but always is present along with involvement of the spine in cases labeled brachyolmia. Horton et al. (1983) described 2 brothers and a sister with this disorder. In addition to universal platyspondyly, they pointed to lateral extension of the vertebral bodies beyond the pedicles and irregularity of the vertebral endplates. Histologic changes on iliac crest biopsy of growth plate were considered typical. Chondrocyte clusters at the growth plate and fibrous cartilage matrix were combined with enlarged chondrocyte lacunae and reciprocal perilacunar loss of glycoaminoglycan and excessive collagen aggregation. Hobaek's families 20 to 26 may be the same as Horton's, and differentiation from the Toledo type of spondyloepiphyseal dysplasia (SED) tarda (271630) was not certain. Shohat et al. (1989) raised the question of whether this disorder is the same as the Toledo form of brachyolmia (271630). The radiologic features are similar, but precocious ossification of costal cartilage is seen in the Toledo type. Shohat et al. (1989) distinguished a Maroteaux type of brachyolmia (613678) on the basis of differences in the conformation of the vertebral bodies. The Maroteaux type may be associated with precocious calcification of the falx cerebri and minor facial anomalies. McKusick (1993) consulted in the case of a Norwegian patient (El.Dr.), 1 of 2 sisters, who may have had brachyolmia of the Hobaek type. Skeletal changes were predominantly in the spine where spinal stenosis was evident throughout the entire length. Precocious calcification of costal cartilages was a striking feature. Height was about 145 cm. The parents, not known to be consanguineous, were of normal stature. One of the sisters had 2 normal children. Hoo and Oliphant (2003) described a brother and sister with brachyolmia and radiologic findings that were thought to be compatible with the Hobaek type. The features were platyspondyly, horizontal acetabular roof, short femoral neck, and vertical 'mixed lucent and dense' striation pattern in the metaphyses of large long bones. Despite normal birth weight and length, the platyspondyly was present at infancy, but clinically the condition was not noticeable until late childhood or early puberty when stunted growth became apparent. Beyond puberty, the patients were short of stature, mainly due to a short trunk with decreased upper and lower body segment ratio. Mukamel et al. (2003) described an 8.5-year-old boy and his 19-year-old sister who had Hobaek-type brachyolmia complicated by spinal stenosis. The parents were healthy, unrelated Jews of Moroccan descent.