169:, 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
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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).
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262:(the formation of bone), particularly in the spine, hips, and limbs where osteogenesis begins with the formation of cartilage, which is then calcified and transformed into bone. We do not yet fully understand the normal function of COMP protein, though it is believed to play a part in cellular growth, division and
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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
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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
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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
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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
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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
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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
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Nearly 60 mutations in the COMP gene have been identified in individuals with pseudoachondroplasia. However, the mutation responsible for the most common allele is a deletion of one codon within a very short triplet repeat (GAC), in which the 469th amino acid, an aspartic acid, is deleted (OMIM
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Exact diagnosis remains widely built on precise history taking, with the characteristic clinical and radiographic skeletal features. Genetic diagnosis is based on DNA sequencing. Because plasma COMP levels are significantly reduced in patients with COMP mutations, such as pseudoachondroplasia,
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Pseudoachondroplasia. Leg radiographs depicting dysplastic distal femoral and proximal tibial epiphyses, and distal femoral metaphyseal broadening, cupping, irregularities (white arrows) and radiolucent areas especially medially. Note the metaphyseal line of ossification of the proximal tibias
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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
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Radiographic findings of the pelvis and hips found in
Perthes disease should not be confused with pseudochondroplasia. Patients with Perthes disease may present with unilateral hip affection. Besides bilateral hip affection are usually asymmetric. In contrast patients with pseudochondroplasia
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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
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Accurate assessment of plain radiographic findings remains an important contributor to diagnosis of pseudoachondroplasia. It is noteworthy that vertebral radiographic abnormalities tend to resolve over time. Epiphyseal abnormalities tend to run a progressive course. Patients usually suffer
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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).
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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).
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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
579:"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"
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Metaphyseal broadening, irregularity and metaphyseal line of ossification. These abnormalities that are typically encountered in proximal humerus and around the knees are collectively known as "rachitic-like
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Normal widening of the interpedicular distances caudally demonstrated on anteroposterior radiographs of the dorsolumbar region. This is an important differentiating feature between pseudoachondroplasia and
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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).
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Hypoplastic capital femoral epiphyses, broad short femoral necks, coxa vara, horizontality of acetabular roof and delayed eruption of secondary ossification center of os pubis and greater trochanter.
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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
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The COMP gene is located on chromosome 19p13.1; its precise locus is P49747. COMP contains 19 exons. The cartilage oligomeric matrix protein is 757 aa (OMIM 2008). COMP protein is found in the
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broadening of the metaphyseal ends of long bones especially around the wrists, knees and ankles. Patients with pseudoachondroplasia have normal intelligence and craniofacial features.
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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).
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due to the inhibition of skeletal growth primarily in the limbs. Though similarities in nomenclature may cause confusion, pseudoachondroplasia should not be confused with
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Together with rhizomelic limb shortening, the presence of epiphyseal-metaphyseal changes of the long bones is a distinctive radiologic feature of pseudoachondroplasia.
153:. Pseudoachondroplasia is caused by a heterozygous mutation in the gene encoding cartilage oligomeric matrix protein (COMP). Mutation in the COMP gene can also cause
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early-onset arthritis of hips and knees. Many unique skeletal radiographic abnormalities of patients with pseudoachondroplasia have been reported in the literature.
283:(blackarrows) and relative sparing of the tibial shafts. The changes around the knee are known as "rachitic-like changes". Lesions are bilateral and symmetrical.
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642:"Serum or plasma cartilage oligomeric matrix protein concentration as a diagnostic marker in pseudoachondroplasia: differential diagnosis of a family"
254:, a complex web of proteins and other molecules that form in the spaces between the cells that make up ligaments and tendons. It is also found near
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Pseudoachondroplasia (also known as PSACH, pseudoachondroplastic dysplasia, and pseudoachondroplastic spondyloepiphyseal dysplasia syndrome) is an
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157:. Despite the radioclinical similarities between pseudoachondroplasia and multiple epiphyseal dysplasia, the latter is less severe.
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714:"A systematized approach to radiographic assessment of commonly seen genetic bone diseases in children: A pictorial review"
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468:"Pseudoachondroplasia in a child: the role of anthropometric measurements and skeletal imaging in differential diagnosis"
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Oval shaped vertebrae with anterior beak originating and platyspondyly demonstrated on lateral radiographs of the spine.
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measuring plasma COMP levels has become a reliable means of diagnosing this and pathopysiologically similar disorders.
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266:(self-destruction) of cells, as well as participating in the regulation of cell movement and attachment (OMIM 2008).
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EL-Sobky, TA; Shawky, RM; Sakr, HM; Elsayed, SM; Elsayed, NS; Ragheb, SG; Gamal, R (15 November 2017).
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Jackson GC, Mittaz-Crettol L, Taylor JA, Mortier GR, Spranger J, Zabel B; et al. (2012).
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and other physical deformities for both affected individuals and their families (OMIM 2008).
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Radiographic lesions of the appendicular skeleton are typically bilateral and symmetric.
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Other causes of genu valgum (knock knees) or genu varum (bow legs) such as rickets
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The references used may be made clearer with a different or consistent style of
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Tufan AC, Satiroglu-Tufan NL, Jackson GC, Semerci CN, Solak S, Yagci B (2007).
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Dysplastic/hypoplastic epiphyses especially of shoulders and around the knees.
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OMIM: Online
Mendelian Inheritance in Man. “Pseudoachondroplasia, PSACH”
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Dwarfism: Medical and
Psychosocial Aspects of Profound Short Stature
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Odontoid hypoplasia may occur resulting in cervical instability.
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258:(cartilage-forming cells). Chondrocytes play a vital role in
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typically exhibit bilateral and symmetric hip involvement.
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is an inherited disorder of bone growth. It is a genetic
531:"Pseudoachondroplasia: report on a South African family"
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The
Egyptian Journal of Radiology and Nuclear Medicine
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466:Gamal R, Elsayed SM, EL-Sobky TA, Elabd HS (2017).
759:. The Johns Hopkins University Press. p. 39.
559:: CS1 maint: DOI inactive as of September 2024 (
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220:Pseudoachondroplasia is inherited in an
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224:manner, though one case of a very rare
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1043:Spondyloepiphyseal dysplasia congenita
397:type IX collagen (Hetch et al. 1995).
353:Spondyloepiphyseal dysplasia congenita
1324:Ullrich congenital muscular dystrophy
1168:Ullrich congenital muscular dystrophy
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1405:Congenital stromal corneal dystrophy
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1289:Otospondylomegaepiphyseal dysplasia
1268:Schmid metaphyseal chondrodysplasia
134:or arising lower limb deformities.
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535:South African Journal of Radiology
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1284:Weissenbacher–Zweymüller syndrome
1193:Epidermolysis bullosa dystrophica
1048:Spondyloepimetaphyseal dysplasia,
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141:that results in mild to severely
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1384:Junctional epidermolysis bullosa
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1389:Laryngoonychocutaneous syndrome
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1467:Scleroprotein and ECM diseases
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1246:Multiple epiphyseal dysplasia
529:Moosa S, Nishimura G (2013).
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340:Multiple epiphyseal dysplasia
155:multiple epiphyseal dysplasia
1472:Autosomal dominant disorders
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718:J Musculoskelet Surg Res
981:Osteogenesis imperfecta
731:10.4103/jmsr.jmsr_28_17
659:10.1038/sj.ejhg.5201882
436:Genetics Home Reference
1296:Type XI collagenopathy
1132:Ehlers–Danlos syndrome
1083:Ehlers–Danlos syndrome
1063:Type II collagenopathy
992:Ehlers–Danlos syndrome
549:(inactive 2024-09-12).
432:"pseudoachondroplasia"
329:Differential diagnosis
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1415:Urbach–Wiethe disease
1252:(types 2, 3, & 6)
1094:Sack–Barabas syndrome
998:(types 1, 2, & 7)
345:Mucopolysaccharidosis
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139:osteochondrodysplasia
292:Skeletal radiography
252:extracellular matrix
210:Pseudoachondroplasia
198:Pseudoachondroplasia
186:Pseudoachondroplasia
124:Pseudoachondroplasia
90:Pseudoachondroplasia
226:autosomal recessive
1346:Bullous pemphigoid
1017:Hypochondrogenesis
866:External resources
595:10.1002/humu.21611
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222:autosomal dominant
161:Signs and symptoms
151:skeletal dysplasia
128:autosomal dominant
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1038:Marshall syndrome
1033:Stickler syndrome
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652:(10): 1023–1028.
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165:Disproportionate
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441:2017-09-27
418:References
54:footnoting
1440:see also
906:GeneTests
724:(2): 25.
363:Treatment
311:changes".
274:Diagnosis
264:apoptosis
111:Specialty
1330:(type 2)
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947:collagen
875:Orphanet
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412:Dwarfism
401:See also
216:Genetics
50:citation
1376:Laminin
951:laminin
604:3272220
384:History
270:2008).
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