The predominant finding of pseudoachondroplasia is irregularity of all long bone metaphyses and epiphyses. The patient was also noted to have genu varum on the right and genu valgum on the left, along with a prominent lumbar lordosis and a mild dextroscoliosis of the thoracic spine. These radiographic findings, in conjunction with the clinical information, are characteristic of pseudoachondroplasia.
DiscussionPseudoachondroplasia is part of the osteochondrodysplasias, a group of disorders characterized by bone and cartilage maldevelopment. Currently, there are >150 distinct conditions described as skeletal dysplasias, and each of these disorders is believed to have a unique genetic etiology. This genetic basis, if present, would result in each disorder having a distinct prevalence, prognosis, and treatment possibility. Although each disorder is thought to be unique, the majority share similar clinical and radiographic features.1 This illustrates the importance of both a good history and physical examination as well as a radiographic knowledge of skeletal dysplasias.
Individuals with pseudoachondroplasia (PSACH) develop short-limbed dwarfism with notable features of joint laxity, early onset degenerative joint disease, metaphyseal and epiphyseal maldevelopment, and vertebral malformations. Pseudoachondroplasia is a type of skeletal osteochondrodysplasia that presents between 2 and 4 years of age. Overall, osteochondrodysplasia has a prevalence of approximately 4 per million and is generally described as a group of disorders with autosomal dominant genetic transmission and with relatively frequent sporadic cases.2
With the aid of an adequate physical examination and history, the diagnosis of pseudoachondroplasia is delineated from other skeletal dysplasias by radiographic findings. The key physical examination features include normal facial appearance and intelligence. The adult height ranges from 82 to 130 cm with a mean height of approximately 118 cm. There is marked shortening of the limbs with limited elbow extension. Patients are also noted to have deformities secondary to osteoarthritis and joint laxity, including cervical spine instability, genu valgum, genu varum, and genu recurvatum. Deformities of the back may include scoliosis, lumbar lordosis, and thoracolumbar kyphosis. Of importance, the first physical examination finding noted by parents or physicians is a disturbance of gait or a deformity of the legs at approximately 2 years of age. The shortened body habitus and extremities then become apparent.
The radiographic features include a normal skull and variable vertebral findings. There may be a persistent oval shape to the vertebral bodies during childhood. Anterior "beaking," platyspondyly, triangular outline, odontoid dysplasia, and disc space widening may also be present. Some relatively less affected patients may have rather normal spines. The long bones are dramatically shortened, have flared metaphyses, and have small epiphyses that appear flared and irregular (Figure 1). These manifestations are most notable in the hands and feet, but may also be seen proximally. In addition to their dysplastic appearance, the development of the epiphyses is also delayed. The acetabulum is usually poorly formed and reveals a widened triradiate cartilage (Figure 2). As with other epiphyses, the capital femoral epiphyses appear late and are small. One finding very characteristic of PSACH is the medial beaking seen in the medial portions of the proximal femoral neck (Figure 2). The maturation in the pelvis is delayed at the triradiate cartilage and ischiopubic ramus. The hands and wrists show delayed maturation, and there is shortening and widening of the phalanges, metacarpals, and metatarsals (Figure 3).
Pseudoachondroplasia appears to develop secondarily to a mutation within the genes encoding for cartilage oligomeric matrix protein (COMP) on chromosome 19 and is most closely related to multiple epiphyseal dysplasia (MED/EDM1), a disorder also characterized by a mutation of the COMP.3 Cartilage oligomeric matrix protein is found in the extracellular matrix of cartilage, tendon, and ligament and, along with type IX collagen, is a key structural component of the cartilage extracellular matrix. These 2 components play a major role in collagen fibrillogenesis, homeostasis, and tissue development. The COMP expressed in tendon and colocalizing with collagen type I may explain the joint laxity seen in PSACH, but that is only a hypothesis at present.4,5
The differential diagnosis for this radiographic appearance in the context of the clinical findings includes achondroplasia, MED, spondyloepiphyseal dysplasia congenita, diastrophic dwarfism, and metatrophic dwarfism. Patients with achondroplasia have a large head with a prominent frontal region and a depressed bridge of the nose. The key differentiating point is that the epiphyses of patients with achondroplasia are normal. The pelvis is square with small sciatic notches but the "trident" feature of the hands in achondroplasia is not seen in PSACH.
Multiple epiphyseal dysplasia is characterized by a near normal pelvis with some scalloping of the acetabular margin. The enlargement of the triradiate cartilage and the poorly formed acetabulae are not seen in this disorder. The patients, however, will also have grossly abnormal epiphyses and premature osteoarthritis, as in PSACH. Spondyloepiphyseal dysplasia congenita, on the other hand, is typified by hip joints that are affected disproportionately in relation to the more distal portion of the lower extremities. In fact, the periphery of the limbs is closer to normal as compared with PSACH. Individuals with diastrophic dwarfism have joint contractures and scoliosis from birth or early infancy. Scoliosis usually presents later and is not always evident in those with PSACH.
Patients with metatrophic dwarfism are classically described as having "dumbbell-shaped" long bones and flattened vertebrae in infancy. There is also substantially less epiphyseal involvement as compared with those with PSACH.
The natural history of pseudoachondroplasia involves progressive degrees of morbidity. Patients with PSACH usually present at 2 to 4 years of age with abnormal gait or extremities and are subsequently noted to have a shortened stature and disproportionately shortened limbs. One study with a limited number of patients noted that although 25% of PSACH patients complained of tingling of limbs, no extraskeletal complications are attributed to this disorder.6 The authors also noted that 75% of patients with genu varum, genu valgum, or genu recurvatum underwent surgical correction. Given the epiphyseal dysplasia and the thin articular cartilage, these individuals are predisposed to early onset and severe degenerative joint disease. Joint replacement is a common procedure that often alleviates much of the morbidity associated with the joint manifestations of PSACH, and patients often undergo this procedure in their early-to mid-thirties. In addition to occurring in the hips, early degenerative joint disease frequently occurs in the lower limbs, shoulders, elbows, ankles, and feet.
Pseudoachondroplasia is a rare autosomal disorder with relatively frequent sporadic cases. Individuals have a normal life span and intelligence, and there are no known extraskeletal manifestations related to PSACH. The most prominent feature of this disease relates to the morbidity from early degenerative joint disease, and individuals with PSACH very often undergo joint replacement surgery for degenerative joint disease. Research is ongoing to understand the genetics and the biology of this disorder, but recent advances may link the mutation of the COMP most closely with forms of MED. Early recognition of this disease is important to facilitate early therapy related to the joint manifestations. With new treatment advancements derived from genetic information, it may soon be important to identify these patients so that they may receive direct COMP-altering therapy to correct this disorder at the gene or protein synthesis level.
- Kornblum M, Stanitski DF. Spinal manifestations of skeletal dysplasia. Orthop Clin North Am.1999;30:501-520.
- Wynne-Davies R, Hall CM, Apley AG.Atlas of Skeletal Dysplasias. New York, NY: Churchill Livingstone; 1985:239-242.
- Hecht JT, Montufar-Solis D, Decker G, et al. Retention of cartilage oligomeric matrix protein (COMP) and cell death in redifferentiated pseudoachondroplasia chondrocytes. Matrix Biol.1998;17: 625-633.
- Holden P, Meadows RS, Chapman KL, et al. Cartilage oligomeric matrix protein interacts with type IX collagen, and disruptions to these interactions identify a pathogenetic mechanism in a bone dysplasia family. J Biol Chem. 2001;276:6046-6055.
- Briggs MD, Hoffman SM, King LM, et al. Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene. Nat Genet.1995;10:330-336.
- McKeand J, Rotta J, Hecht JT. Natural history of pseudoachondroplasia. Am J Med Genet. 1996;63:406-410.