Pseudoachondroplasia is an inherited disorder of bone growth.^[1] It is a genetic autosomal dominant disorder. It is generally not discovered until 2–3 years of age, since growth is normal at first. Pseudoachondroplasia is usually first detected by a drop of linear growth in contrast to peers, a waddling gait or arising lower limb deformities.^[2]

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Pseudoachondroplasia
Pseudoachondroplasia. Shoulders and Humeri. Note the dysplastic proximal humeral epiphyses, metaphyseal broadening, irregularity and metaphyseal line of ossification. These changes are collectively known as "rachitic-like changes". Lesions are bilateral and symmetrical.
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Pseudoachondroplasia (also known as PSACH, pseudoachondroplastic dysplasia, and pseudoachondroplastic spondyloepiphyseal dysplasia syndrome) is an osteochondrodysplasia that results in mild to severely short stature due to the inhibition of skeletal growth primarily in the limbs.^[2] Though similarities in nomenclature may cause confusion, pseudoachondroplasia should not be confused with achondroplasia, which is a clinically and genetically distinct skeletal dysplasia. Pseudoachondroplasia is caused by a heterozygous mutation in the gene encoding cartilage oligomeric matrix protein (COMP). Mutation in the COMP gene can also cause multiple epiphyseal dysplasia. Despite the radioclinical similarities between pseudoachondroplasia and multiple epiphyseal dysplasia, the latter is less severe.^[3]

Disproportionate short stature, deformity of the lower limbs, short fingers, and ligamentous laxity give pseudoachondroplasia its distinctive features. The average height of adult males with the condition is around 120 centimeters (3 ft, 11 in), while adult females are typically around 116 cm (3 ft, 9in). Affected individuals are not noticeably short at birth. Patients with pseudoachondroplasia present with gait abnormalities, lower limb deformity, or a retarded growth rate that characteristically appear at age 2–3 years. Disproportionate short stature is characterized by shortening of proximal limb segments (humeri and femora) also called rhizomelic shortening. Other known clinical features include, genu valgum/varum, brachydactyly (short fingers), supple flexion deformity of the hips, knees, hyperlordosis of lumbar spine, rocker bottom feet and broadening of the metaphyseal ends of long bones especially around the wrists, knees and ankles. Patients with pseudoachondroplasia have normal intelligence and craniofacial features.^[2][4][5]

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Pseudoachondroplasia is inherited in an autosomal dominant manner, though one case of a very rare autosomal recessive form has been documented. The offspring of affected individuals are at 50% risk of inheriting the mutant allele. Prenatal testing by molecular genetic examination is available if the disease-causing mutation has been identified in an affected family member (Hecht et al. 1995).

COMP is an extracellular calcium binding protein directly involved in chondrocyte migration and proliferation. It is observed at a high frequency in chondrocytes in developing bone and tendon. In pseudochondroplasia, COMP is not secreted, but instead collects in the chondrocytes, ultimately poisoning and killing them. Though some chondrocytes do manage to survive, growth is significantly reduced, resulting in the characteristically short limbs and seemingly unaffected face and torso of those inflicted with the disorder (OMIM 2008). Mutations in COMP result in a phenotypic spectrum that varies from pseudochondroplasia (at the most extreme end) to multiple epiphyseal dysplasia or MED (a genetically similar, though milder skeletal dysplasia).^[5]

Studies conducted by Hetch et al. suggest that type IX collagen, a collagen active specifically in the construction of cartilage, plays a key role in pseudoachondroplasia. The researchers found that IX collagen was amassed within the pseudoachondroplasia chondrocytes. This discovery suggests that the pathogenesis of pseudoachondroplasia involves the interactions of the mutant COMP gene products with specific cartilage components, such as type IX collagen, and that it is not solely the result of the effects of mutant molecules on the production and secretion of COMP (OMIM 2008).

Exact diagnosis remains widely built on precise history taking, with the characteristic clinical and radiographic skeletal features.^[2][4] Genetic diagnosis is based on DNA sequencing. Because plasma COMP levels are significantly reduced in patients with COMP mutations, such as pseudoachondroplasia, measuring plasma COMP levels has become a reliable means of diagnosing this and pathopysiologically similar disorders.^[6]

There is currently no cure for pseudoachondroplasia. However, management of the various health problems that result from the disorder includes medications such as analgesics (painkillers) for joint discomfort, osteotomy for lower limb deformities, and the surgical treatment of scoliosis. Prevention of some related health problems includes physical therapy to preserve joint flexibility and regular examinations to detect degenerative joint disease and neurological manifestations (particularly spinal cord compression). Additionally, healthcare providers recommend treatment for psychosocial issues related to short stature and other physical deformities for both affected individuals and their families (OMIM 2008).

Pseudoachondroplasia is one of the most common skeletal dysplasias affecting all racial groups. However, no precise incidence figures are currently available (Suri et al. 2004).

In 1995 the gene responsible for Pseudoachondroplasia was identified by a research team led by Dr. Jacqueline Hecht of The University of Texas-Houston, Health Science Center. This discovery additionally shed light on the COMP protein, which the team recognized as somehow involved in skeletal growth and height determination (Hetch et al. 1995).^[8]

In 1997, Hetch and her colleagues from the Research Department at Shriners Hospital for Children in Portland, Oregon conducted further research, which led to their discovery that the intracellular fate of mutant COMP is determined by the environment of individual chondrocytes, contrary to the previous notion that COMP activities leading to Pseudoachondroplasia were determined by structural effects of the mutation on COMP; this meant that COMP activities are cell-specific (Hetch et al. 1995).

Hetch et al. also discovered type IX collagen accumulated within the Pseudoachondroplasia chondrocytes. This discovery indicated the pathogenesis of Pseudoachondroplasia results from the interactions of the products of the mutant COMP allele with certain “cartilage components,” particularly with type IX collagen (Hetch et al. 1995).

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