Alternative titles; symbols
Other entities represented in this entry:
ORPHA: 85166; DO: 0111508;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12q13.11 | Platyspondylic skeletal dysplasia, Torrance type | 151210 | Autosomal dominant | 3 | COL2A1 | 120140 |
A number sign (#) is used with this entry because the Torrance type of platyspondylic lethal skeletal dysplasia (PLSDT) is caused by heterozygous mutation in the COL2A1 gene (120140) on chromosome 12q13.
The Torrance type of platyspondylic lethal skeletal dysplasia (PLSDT) is an autosomal dominant disorder characterized by varying platyspondyly, short ribs with anterior cupping, hypoplasia of the lower ilia with broad ischial and pubic bones, and shortening of the tubular bones with splayed and cupped metaphyses. Histology of the growth plate typically shows focal hypercellularity with slightly enlarged chondrocytes in the resting cartilage and relatively well-preserved columnar formation and ossification at the chondroosseous junction. Though generally lethal in the perinatal period, longer survival has been reported (summary by Zankl et al., 2005).
Horton et al. (1979) described an infant (patient 11) with a form of platyspondylic lethal skeletal dysplasia (PLSD) that they designated the Torrance type (PLSDT). Radiologically, the Torrance variety is characterized by decreased ossification of the skull base, disc-like platyspondyly, short thin ribs, hypoplastic pelvis with wide sacrosciatic notches and flat acetabular roof, and short tubular long bones with metaphyseal cupping. Histologically, the growth plate appeared relatively normal. The resting cartilage appeared hypercellular with large chondrocytes.
Winter and Thompson (1982) described another form of platyspondylic lethal skeletal dysplasia, which they called the Luton type (PLSDL), in a stillborn male infant. X-ray features were similar to those in PLSDT. Chondroosseous morphology showed hypercellular resting cartilage, and chondrocytes were irregular, ballooned, and arranged in clusters. PLSDL is considered to be a mild phenotypic variant of PLSDT (Nishimura et al., 2004).
Omran et al. (2000) reported an affected mother who gave birth to an affected daughter who died soon after birth. Both mother and daughter were described as having a large head, coarse facial features, depressed nasal bridge, protuberant abdomen, and severe micromelia.
Neumann et al. (2003) reported an additional family with survival to adulthood and dominant transmission of the Torrance-Luton type of platyspondylic chondrodysplasia and additional radiographs of the family described by Omran et al. (2000). Newborn radiographs demonstrated insufficient ossification of the anterior portions of the vertebral bodies and platyspondyly. In surviving patients, ossification of the vertebral bodies improved but the upper and lower endplates remained irregular. At birth, the long tubular bones were short and broad with smooth or slightly ragged metaphyseal borders. Survivors had short tubular bones with distinct metaphyseal flaring.
The transmission pattern of PLSDT in 2 families reported by Zankl et al. (2005) was consistent with autosomal dominant inheritance.
In each of 2 patients with the Torrance type of platyspondylic skeletal dysplasia, Nishimura et al. (2004) identified a de novo mutation in the COL2A1 gene (120140.0039 and 120140.0040, respectively). The former patient was stillborn and the latter, who demonstrated evolution of the phenotype into that of Kniest-like dysplasia (see 156550), was still alive at 5 years of age at the time of report.
Zankl et al. (2005) studied 8 additional cases of PLSDT and found that all had mutations in the C-propeptide domain of COL2A1, including the families described by Omran et al. (2000) and Neumann et al. (2003). The mutational spectrum included missense, stop codon, and frameshift mutations. All nonsense mutations were located in the last exon, where they would escape nonsense-mediated RNA-decay. Zankl et al. (2005) concluded that PLSDT is caused by mutations in the C-propeptide domain of COL2A1, which lead to biosynthesis of an altered collagen chain (as opposed to a null allele). Similar mutations cause spondyloperipheral dysplasia (see 271700), a nonlethal dominant disorder whose clinical and radiographical features overlap those of the rare long-term survivors with PLSDT.
Exclusion Studies
Brodie et al. (1999) searched for mutations in the FGFR3 gene (134934) in 22 cases of thanatophoric dysplasia variants; no mutations were identified in cases of the Torrance or Luton types.
Brodie, S. G., Kitoh, H., Lachman, R. S., Nolasco, L. M., Mekikian, P. B., Wilcox, W. R. Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations. Am. J. Med. Genet. 84: 476-480, 1999. [PubMed: 10360402]
Horton, W. A., Rimoin, D. L., Hollister, D. W., Lachman, R. S. Further heterogeneity within lethal neonatal short-limbed dwarfism: the platyspondylic types. J. Pediat. 94: 736-742, 1979. [PubMed: 448481] [Full Text: https://doi.org/10.1016/s0022-3476(79)80140-7]
Neumann, L., Kunze, J., Uhl, M., Stover, B., Zabel, B., Spranger, J. Survival to adulthood and dominant inheritance of platyspondylic skeletal dysplasia, Torrance-Luton type. Pediat. Radiol. 33: 786-790, 2003. [PubMed: 12961049] [Full Text: https://doi.org/10.1007/s00247-003-1055-x]
Nishimura, G., Nakashima, E., Mabuchi, A., Shimamoto, K., Shimamoto, T., Shimao, Y., Nagai, T., Yamaguchi, T., Kosaki, R., Ohashi, H., Makita, Y., Ikegawa, S. Identification of COL2A1 mutations in platyspondylic skeletal dysplasia, Torrance type. J. Med. Genet. 41: 75-79, 2004. [PubMed: 14729840] [Full Text: https://doi.org/10.1136/jmg.2003.013722]
Omran, H., Uhl, M., Brandis, M., Wilff, G. Survival and dominant transmission of 'lethal' platyspondylic dwarfism of the 'West coast' types. J. Pediat. 136: 411-413, 2000. [PubMed: 10700704] [Full Text: https://doi.org/10.1067/mpd.2000.103443]
Winter, R. M., Thompson, E. M. Lethal, neonatal, short-limbed platyspondylic dwarfism: a further variant? Hum. Genet. 61: 269-272, 1982. [PubMed: 7173874] [Full Text: https://doi.org/10.1007/BF00296459]
Zankl, A., Neumann, L., Ignatius, J., Nikkels, P., Schrander-Stumpel, C., Mortier, G., Omran, H., Wright, M., Hilbert, K., Bonafe, L., Spranger, J., Zabel, B., Superti-Furga, A. Dominant negative mutations in the C-propeptide of COL2A1 cause platyspondylic lethal skeletal dysplasia, Torrance type, and define a novel subfamily within the type 2 collagenopathies. Am. J. Med. Genet. 133A: 61-67, 2005. [PubMed: 15643621] [Full Text: https://doi.org/10.1002/ajmg.a.30531]