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]

  If short stature is present, it is usually mild. Body proportions are normal although the fingers may be short and joint laxity is often excessive. Osteoarthritis is a major complication. [ommbid.mhmedical.com]

  The short stature becomes more prominent with age and the hands and feet appear short and wide. Joint laxity is a general feature, but predominantly affects the hands. Defective epiphyseal growth causes early arthrosis. [orpha.net]

• Disproportionate Short Stature

  Abstract Pseudoachondroplasia (PSACH) is an autosomal dominant dwarfing condition associated with disproportionate short stature, marked joint deformities, and early onset osteoarthritis. [ncbi.nlm.nih.gov]

• Short Finger

  Referral at 9 years for investigation of bilateral hip and left knee pain confirmed short stature, 107 cm (<3rd centile), with rhizomelic limb shortening, short fingers, and a waddling gait. [jmg.bmj.com]

  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

  The adult height usually ranges between 82–130 cm with marked shortening of limbs. Associated deformities include genu valgum/varus, genu reccurvatum, limited elbow extension, kyphoscoliosis or increased lumbar lordosis, and joint laxity with secondary [slideshare.net]

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

  Deformities of the back may include scoliosis, lumbar lordosis, and thoracolumbar kyphosis. [appliedradiology.com]

  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]

• Genu Valgum

  valgum, or genu recurvatum underwent surgical correction. [appliedradiology.com]

  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]

  Also found in: Acronyms, Wikipedia. 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 [medical-dictionary.thefreedictionary.com]

  Multiple other skeletal features include genu valgum, genu vara, or “windswept deformities” of the legs, limitations of elbow extension, ulnar deviation of the hand, scoliosis, and odontoid hypoplasia. Osteoarthritis and painful joints are common. [ommbid.mhmedical.com]

• 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]

• 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]

  Other 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. [rareguru.com]

  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]

  Other 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. [littlepeopledoc.com]

• Coxa Vara

  - extremities: - long bones are characterized by epiphyseal, metaphyseal, and physeal changes; - this uneven growth leads to joint incongruity and malalignment; - precocious arthritis is a major complication, as in other epiphyseal dysplasias; - coxa [wheelessonline.com]

  Clinical description Clinical manifestations may include short stature with a very short trunk and neck and shortened limbs, clubfoot, coxa vara, cleft palate, flat facial features, hypertelorism, eye abnormalities (nystagmus, congenital cataracts, glaucoma [orpha.net]

  Diagnostic Considerations Other conditions to be considered in the diagnosis include the following: Bilateral Legg-Calvé-Perthes disease - Patients with this condition may have normal stature; features of multiple epiphyseal dysplasia (MED) include coxa [emedicine.staging.medscape.com]

  Numerous diagnoses, including spondyloepiphyseal dysplasia congenita with coxa vara and Morquio's syndrome, were considered followingx ray examination. [jmg.bmj.com]

• Suggestibility

  Type II collagen was solely found in the ECM suggesting that it is processed and transported differently from other retained ECM proteins. [ncbi.nlm.nih.gov]

  The results of this study suggest that autosomal recessive inheritance is unlikely and all cases of PSACH should be studied for mutations in COMP. [scienceopen.com]

  These observations suggest that the normal function of FGFR3 is necessary for negative regulation of bone growth. [ommbid.mhmedical.com]

• Waddling Gait

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

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

  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]

  A delay in walking or an abnormal gait is often the first clinical clue. By this time, body measurements clearly reveal the disproportionate short stature. [musculoskeletalkey.com]

  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]

  The clinical features include abnormal gait, short limbs, short fingers/toes, scoliosis, bracelet sign, ankle sign and other skeletal deformities. COMP is the pathogenic gene and mutations mainly located in calmodulin-like domains. [pesquisa.bvsalud.org]

• Cervical Cord Compression

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

  cord compression 0002341 Childhood onset short-limb short stature 0011405 Delayed epiphyseal ossification 0002663 Flared femoral metaphysis 0002834 Fragmented epiphyses Fragmented end part of bone 0100168 Fragmented, irregular epiphyses Fragmented, irregular [rarediseases.info.nih.gov]

  The progress can be retarded by in taking vitamin D but finally, most of patients need surgical intervention to correct deformities and cervical stabilization procedures to alleviate neurologic symptoms and signs of cervical cord compression (Li, Song [scirp.org]

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].

Management and treatment Treatment is based on physiotherapy, management of the spinal deformation and corrective orthopedic surgery. Intensive physical activity should be avoided. [orpha.net]

Toward identifying potential treatments, drugs known to decrease cellular stress (lithium, phenylbutyric acid, and valproate) were assessed. [ncbi.nlm.nih.gov]

These tests may include: Imaging tests such as X-rays, MRIs and CT scans and EOS imaging Physical exam Genetic testing Treatment Our expert doctors will determine the best course of treatment based on multiple factors. [ortho-institute.org]

Before taking any medication, always check with a qualified professional for healthcare information, treatment advice. [rarediseases.oscar.ncsu.edu]

Prognosis The final height prognosis is variable but the short stature may be moderately severe. The documents contained in this web site are presented for information purposes only. [orpha.net]

The description and natural history of the double heterozygote phenotype may be useful in counseling families regarding risk and prognosis. [ncbi.nlm.nih.gov]

Prognosis The prognosis for most people with pseudoachondroplasia is very good. In general, they have minimal medical problems, normal IQ, and most achieve success and have a long life, regardless of their stature. [encyclopedia.com]

[…] synonyms: Pseudoachondroplasia ICD-9 756.4 Chondrodystrophy Pseudoachondroplasia Etiology / Epidemiology / Natural History Disproportionate short-limbed dwarfism and ligamentous laxity Caused by deletion or alteration of the gene coding for Cartilage [eorif.com]

Etiology The disorder is caused by small mutations or deletions in the COMP gene (19p13.1) coding for the cartilage oligomeric matrix protein. [orpha.net]

Pseudoachondroplasia and multiple epiphyseal dysplasia: New etiologic developments. Source/Author: Unger S, Hecht JT. Am J Med Genet. 2001 Winter;106(4):244-50. Abstract Discussion of the genetic etiology of MED and pseudoachondroplasia. [lpamrs.memberclicks.net]

[…] synonyms: Pseudoachondroplasia ICD-9 756.4 Chondrodystrophy Pseudoachondroplasia Etiology / Epidemiology / Natural History Disproportionate short-limbed dwarfism and ligamentous laxity Caused by deletion or alteration of the gene coding for Cartilage [eorif.com]

Summary Epidemiology Prevalence is estimated at around 1/60,000. Clinical description The disorder is usually discovered during the second year of life with the onset of slow growth and walking difficulties. [orpha.net]

Pathophysiology[edit] 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. [en.wikipedia.org]

COMP trapped in the ER builds an intracellular matrix network that may prevent the normal cellular clearance mechanisms. [ncbi.nlm.nih.gov]

We strive to maximize children’s mobility, correct deformity, and prevent future complications. [nemours.org]

Early death of the chondrocytes prevents normal bone growth and causes the short stature and bone abnormalities seen in pseudoachondroplasia. [ghr.nlm.nih.gov]

Early death of the chondrocytes prevents normal bone growth and causes the short stature and bone abnormalities seen in pseudoachondroplasia. The Gene Associated with Pseudoachondroplasia COMP 4. [encyclopedia.pub]

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.