Identification of COL2A1 mutations in platyspondylic skeletal dysplasia, Torrance type

Platyspondylic lethal skeletal dysplasias (PLSDs) are a heterogeneous group of chondrodysplasias characterised by severe platyspondyly and limb shortening. The most common form of PLSD is thanatophoric dysplasia (TD), which has been divided into two types, TD1 (MIM 187600) and TD2 (MIM 187610). Three other types of PLSD, or TD variants have been distinguished from TD, the San Diego (PLSD-SD; MIM 270230), Torrance (PLSD-T; MIM 151210), and Luton (PLSD-L; MIM 151210) types.1,2 PLSD-L is now considered to be a mild phenotypic variant of PLSD-T. Mutations in the fibroblast growth factor receptor 3 ( FGFR3 ) gene were identified in TD and PLSD-SD,3 but not in PLSD-T and PLSD-L.3,4 PLSD-T is a common subtype of PLSD.2 The radiological characteristics include wafer-like vertebral bodies, severe hypoplasia of the lower ilia, extremely short long bones with ragged metaphyses, and bowing of the radius. Its chondro-osseous histology is characterised by hypercellularity with slightly large chondrocytes in the resting cartilage and normal columnisation with incorporation of cartilage into bone at the chondro-osseous junction.1,2 These radiological and histological findings of the disorder can be used to discriminate it from other lethal or semilethal skeletal dysplasias including TD. Perinatal death is generally considered to be inevitable in PLSD-T. Recently, however, non-lethal phenotypes of the disorder with better ossified vertebral bodies have been proposed, based on the observations of two affected families. One family included an affected mother who survived to adulthood and her affected daughter who died soon after birth,5,6 and the other family included an affected mother and her son, both of whom are living.4 These observations raise the question of whether PLSD-T represents a single entity with a wide clinical spectrum or a heterogeneous group of disorders with superficial radiological similarities. Here we describe two examples of …