Signs and symptoms of pseudoachondroplasia (PSACH) arise because of mutations in the COMP gene that codes for a family of proteins essential for numerous physiological processes in the extracellular matrix of chondrocytes and other soft tissue cells [1]. These mutations lead to premature death of chondrocytes during bone growth, resulting in the transformation of cartilage into bone and subsequent impairment in musculoskeletal growth [1]. Unlike many disorders of insufficient growth in which symptoms present from birth, pseudoachondroplasia (PSACH) is distinguished by a slightly delayed onset of symptoms, as newborns and infants suffering from this condition do not exhibit any signs until early childhood [1] [2]. Short stature, often severe enough to be termed dwarfism, appears during the second year of life, along with various musculoskeletal abnormalities [1] [2] [3]. Deceleration of linear growth, lower extremity bowing and a waddling gait, all lead to rhizomelic dwarfism, while the adult heights range between 82-130 cm with shortening of limbs [1] [4] [5]. In addition, joint changes include profound laxity, pain and a significant reduction in mobility due to osteoarthritis, a cardinal feature of PSACH that affects all joints, particularly the shoulders, elbows, and hips [1]. In fact, severe joint pain and degenerative osteoarthritis in PSACH frequently require hip replacement [1]. Brachydactyly, a knock knee, lumbar lordosis, scoliosis, ulnar deviation of the hands are other notable signs of this genetic disease [1] [6]. Normal head circumference and size, the absence of facial changes and preserved mental growth are important characteristics of PSACH, as craniofacial and intellectual abnormalities are more common in other similar disorders (for eg. achondroplasia) [1] [6].

• Short Stature

  Mutations in exon 13 (encoding the seventh calmodulin-like repeat) have been associated with severe short stature (-6 SD) in PSACH. We examined an Inuit boy with PSACH and severe short stature. [ncbi.nlm.nih.gov]

  Short stature, often severe enough to be termed dwarfism, appears during the second year of life, along with various musculoskeletal abnormalities. [symptoma.com]

• Short Finger

  Despite the radioclinical similarities between pseudoachondroplasia and multiple epiphyseal dysplasia, the latter is less severe. [3] Signs and symptoms [ edit ] Disproportionate short stature, deformity of the lower limbs, short fingers, and ligamentous [en.wikipedia.org]

• Difficulty Walking

  They often have difficulty walking (waddling gait) or have a deformed thoracic cavity and sternum; the thoracic cavity sticks out dramatically in the front of the torso. [aqppt.org]

• Lordosis

  With age, her rhizomelic dwarfism became increasingly visible, and since completed 15 months of age, when she started to walk, the disease was complicated with genu varum, lumbar lordosis and abnormal gait. [ncbi.nlm.nih.gov]

  The case of the current report also had lumbar lordosis ( Figure 1 ). Lumbar lordosis is observed in around 50% of affected individuals ( 4 ). [comprped.com]

  As the growth rate slows, the trunk appears long with lumbar lordosis and rhizomelic shortening of the limbs. Final adult height is 80-130cm. A height curve is available for individuals with pseudoachondroplasia. [web.archive.org]

  Spinal abnormalities are common and include abnormal curvature of the spine like exaggerated lumbar lordosis, kyphosis, and mild to moderate scoliosis. [boneandspine.com]

  Brachydactyly, a knock knee, lumbar lordosis, scoliosis, ulnar deviation of the hands are other notable signs of this genetic disease. [symptoma.com]

• Genu Valgum

  Legs are malaligned with a variety of knee deformities noted, including bow-legs (genu varum), knock-knees (genu valgum), and windswept deformities (bow-leg on one side and knock-knee on the other side). [web.archive.org]

  […] pseu·do·a·chon·dro·pla·si·a ( sū'dō-ă-kon'drō-plā'sē-ă ), A skeletal dysplasia characterized by short-limb dwarfism with leg deformities associated with genu varum or genu valgum and ligamentous laxity, allowing the joints to telescope; normal appearing [medical-dictionary.thefreedictionary.com]

  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. [appliedradiology.com]

  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 [en.wikipedia.org]

• Short Arm

  The disease genes in families with PSACH and MED have been localized to an 800 kilobase interval on the short arm of chromosome 19. Recently the gene for cartilage oligomeric matrix protein (COMP) was localized to chromosome 19p13.1. [ncbi.nlm.nih.gov]

  This process is due to mutations in the gene cause COMP, located on the short arm of chromosome 19 (19p13.1). This gene encodes a protein that is essential for normal cartilage development and for conversion to bone. [ivami.com]

  Characteristic features of pseudoachondroplasia include short arms and legs, a waddling walk, early-onset joint pain (osteoarthritis), and a limited range of motion at the elbows and hips. [sumerdoc.blogspot.com]

  Other characteristic features of pseudoachondroplasia include short arms and legs; a waddling walk; joint pain in childhood that progresses to a joint disease known as osteoarthritis ; an unusually large range of joint movement ( hyperextensibility ) [ghr.nlm.nih.gov]

  Symptoms of pseudoachondroplasia include short arms and legs that do not become apparent until the child is age 3 to 5, bowed legs, scoliosis (curved spine), joint pain, limited range of motion of the joints and other symptoms. [nicklauschildrens.org]

• Brachydactyly

  A 2.75-year-old Chinese boy presented with typical clinical features of pseudoachondroplasia, including disproportionate short-limb short stature, brachydactyly, genu varus and waddling gait. [ncbi.nlm.nih.gov]

  Brachydactyly, a knock knee, lumbar lordosis, scoliosis, ulnar deviation of the hands are other notable signs of this genetic disease. [symptoma.com]

  Definition A skeletal dysplasia usually manifesting in the second year of life and characterized by moderate to severe disproportionate short stature, deformity of the lower limbs, brachydactyly, ligamentous laxity, and degenerative joint disease. [uniprot.org]

• Arthralgia

  Esra Döğer, Aysun Bideci, Öznur Boyunağa, Aylin Kılınç Uğurlu, Emine Demet Akbaş, Orhun Çamurdan & Peyami Cinaz Aim: Pseudoacondroplasia is a short extremity dwarfism characterized by lifelong arthralgia and early onset osteoarthritis. [abstracts.eurospe.org]

  Osteoarthritis in early adulthood is a universal finding usually developing into chronic joint pain (arthralgia). The hips, ankles, shoulder, elbows and wrists are particularly affected. [rarediseases.org]

• Distractibility

  Distraction osteogenesis was used in 20 segments and acute deformity correction was done in six segments. External fixation was applied to all segments. [ncbi.nlm.nih.gov]

• Waddling Gait

  A characteristic waddling gait is seen due to hip involvement. [web.archive.org]

  A 5-year-old boy was admitted to the hospital with failure to thrive since he was 2 years old, with weakness in his legs and a waddling gait. He has normal mental development. His parents are normal phenotypically and are unrelated. [ncbi.nlm.nih.gov]

  Even though waddling gait is present, yet, is less consistent when compared to pseudoachondroplasia. The spine is usually normal ( 4, 5 ). [comprped.com]

• Abnormal Gait

  With age, her rhizomelic dwarfism became increasingly visible, and since completed 15 months of age, when she started to walk, the disease was complicated with genu varum, lumbar lordosis and abnormal gait. [ncbi.nlm.nih.gov]

  By this point the abnormal gait is present and measurements show the short stature to suggest pseudoachondroplasia. Diagnosis is typically made between 1 and 4 years of age. Disease-specific charts should be used to monitor growth. [web.archive.org]

  By this point the abnormal gait is present and measurements suggest pseudoachondroplasia. Diagnosis is typically made between 1 and 4 years of age and is based on clinical examination and characteristic X-ray appearances. [nemours.org]

  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. [appliedradiology.com]

• Cervical Cord Compression

  Death is usually secondary to respiratory compromise or from cervical cord compression by a very small foramen magnum. [ommbid.mhmedical.com]

  Cervical cord compression myelopathy is a complication of this condition. [genedx.com]

• Vertigo

  At 26 years of age he complained of pain in the knees, swallowing difficulties, and vertigo. Renal ultrasonographic examination showed a large cortical cyst of the right kidney and smaller cysts in both kidney. [ncbi.nlm.nih.gov]

The diagnosis of PSACH is difficult to make at birth and during infancy due to the absence of typical features, but when signs of short stature and accompanying joint-related symptoms appear, a detailed workup is necessary to determine the underlying cause [6]. Firstly, a thorough patient history is necessary, primarily to assess the appearance of symptoms and their course. A family history, however, may be vital, as autosomal dominant (but also recessive) patterns of inheritance have been assumed, but because many mutations arise de novo (sporadically), the absence of a positive family history should not rule out PSACH from the differential diagnosis [2] [6]. Physical examination of the child can provide sufficient details to form valid clinical suspicion, in which case radiographic studies should be advised. Plain radiography of all bones in the body must be carried out, as prominent shortening of the proximal segments of long bones (the humerus and femur are predominantly affected), flared and irregular metaphyses, flattened femoral heads, incomplete formation of the acetabulum, a widened pubic symphysis, kyphoscoliosis and a normal radiography of the skull are notable features on X-ray [1] [6]. When clinical and radiologic findings point to PSACH as a probable cause, genetic studies are indicated, when mutations in the COMP gene, mapped on chromosome 4q35, are identified through molecular analysis [2] [6].

1. Posey KL, Alcorn JL, Hecht JT. Pseudoachondroplasia/COMP — translating from the bench to the bedside. Matrix biology : journal of the International Society for Matrix Biology. 2014;0:167-173.
2. Jackson GC, Mittaz-Crettol L, Taylor JA, et al. Pseudoachondroplasia and Multiple Epiphyseal Dysplasia: A 7-Year Comprehensive Analysis of the Known Disease Genes Identify Novel and Recurrent Mutations and Provides an Accurate Assessment of Their Relative Contribution. Hum Mutat. 2012;33(1):144-157.
3. Kennedy J, Jackson G, Ramsden S, et al. COMP mutation screening as an aid for the clinical diagnosis and counselling of patients with a suspected diagnosis of pseudoachondroplasia or multiple epiphyseal dysplasia. European journal of human genetics : Eur J Hum Genet. 2005;13(5):547-555.
4. Elliott AM, Bocangel P, Reed MH, Greenberg CR. A novel COMP mutation in an Inuit patient with pseudoachondroplasia and severe short stature. Genet Mol Res. 2010;9(3):1785-1790.
5. Tandon A, Bhargava SK, Goel S, Bhatt S. Pseudoachondroplasia: A rare cause of rhizomelic dwarfism. Indian Journal of Orthopaedics. 2008;42(4):477-479.
6. Radlović V, Smoljanić Z, Radlović N, et al. Pseudoachondroplasia: a case report. Srp Arh Celok Lek. 2013;141(9-10):676-699.