Multiple epiphyseal dysplasia
Multiple epiphyseal dysplasia | |
---|---|
Specialty | Medical genetics |
Duration | Lifelong |
Multiple epiphyseal dysplasia (MED), also known as Fairbank's disease, is a rare
Signs and symptoms
Children with autosomal dominant MED experience
By adulthood, people with MED are of short stature or in the low range of normal and have short limbs relative to their trunks. Frequently, movement becomes limited at the major joints, especially at the elbows and hips. However, loose knee and finger joints can occur. Signs of osteoarthritis usually begin in early adulthood.[3]
Children with recessive MED experience joint pain, particularly of the hips and knees, and commonly have deformities of the hands, feet, knees, or
Genetics
Multiple epiphyseal dysplasia (MED) encompasses a spectrum of skeletal disorders, in which are inherited in an autosomal dominant form. However, there is an autosomal recessive form.[4]
Associated genes include
Types include:
Type | OMIM | Gene |
---|---|---|
EDM1 | 132400 | COMP |
EDM2 | 600204 | COL9A2
|
EDM3 | 600969 | COL9A3
|
EDM4 | 226900 | DTDST
|
EDM5 | 607078 | MATN3
|
EDM6 | 120210 | COL9A1
|
In the
The
- Level 1: COMP (exons 10–15) and MATN3 (exon 2)
- Level 2: COMP (exons 8 & 9 and 16–19)
- Level 3: COL9A1 (exon 8), COL9A2 and COL9A3 (exon 3)
All those genes are involved in the production of the extracellular matrix (ECM). The role of COMP gene remains unclear. It is a noncollagenous protein of the ECM.[12] Mutations in this gene can cause the pseudoachondroplasia (PSACH). It should play a role in the structural integrity of cartilage by its interaction with other extracellular matrix proteins and can be part of the interaction of the chondrocytes with the matrix and it is also a potent suppressor of apoptosis in chondrocytes. Another role is maintaining a vascular smooth muscle cells contractile under physiological or pathological stimuli.[13]
Since 2003, the European Skeletal Dysplasia Network has used an online system to diagnose cases referred to the network before mutation analysis to study the mutations causing PSACH or MED.[14]
In the
Diagnosis
Diagnosis should be based on the clinical and radiographic findings and a genetic analysis can be assessed.[17]
Treatment
Symptomatic individuals should be seen by an orthopedist to assess the possibility of treatment (physiotherapy for muscular strengthening, cautious use of analgesic medications such as nonsteroidal anti-inflammatory drugs). Although there is no cure, surgery is sometimes used to relieve symptoms.[18] Surgery may be necessary to treat misalignment of the hip (osteotomy of the pelvis or the collum femoris) and, in some cases, malformation (e.g., genu varum or genu valgum).[19] In some cases, total hip replacement may be necessary. However, surgery is not always necessary or appropriate.[20]
Sports involving joint overload are to be avoided, while swimming or cycling are strongly suggested.[21] Cycling has to be avoided in people having ligamentous laxity.
Weight control is suggested.[22] [citation needed]
The use of crutches, other deambulatory aids or wheelchair is useful to prevent hip pain.[23] Pain in the hand while writing can be avoided using a pen with wide grip.[24]
History
Multiple epiphyseal dysplasia was described separately by Seved Ribbing and Harold Arthur Thomas Fairbank in the 1930s.[3]
In 1994, Ralph Oehlmann's group mapped MED to the peri-centromeric region of chromosome 19, using genetic linkage analysis.[25] Michael Briggs' group mapped PSACH to the same area.[26] COMP gene was firstly linked to MED and PSACH in 1995.[27] In 1995, the group led by Knowlton did a "high-resolution genetic and physical mapping of multiple epiphyseal dysplasia and pseudoachondroplasia mutations at chromosome 19p13.1-p12."[28]
Research on COMP led to mouse models of the pathology of MED. In 2002, Svensson's group generated a COMP-null mouse to study the COMP protein in vivo. These mice showed no anatomical, histological, or even ultrastructural abnormalities and none of the clinical signs of PSACH or MED. Lack of COMP was not compensated for by any other protein in the thrombospondin family. This study confirmed that the disease is not caused by reduced expression of COMP.[29]
In 2007, Piròg-Garcia's group generated another mouse model carrying a mutation previously found in a human patient. With this new model, they were able to demonstrate that reduced cell proliferation and increased apoptosis are significant pathological mechanisms involved in MED and PSACH.[30] In 2010, this mouse model allowed a new insight into myopathy and tendinopathy, which are often associated with PSACH and MED. These patients show increased skeletal muscle stress, as indicated by the increase in myofibers with central nuclei. Myopathy in the mutant mouse results from underlying tendinopathy, because the transmission of forces is altered from the normal state. There is a higher proportion of larger diameter fibrils of collagen, but the cross-sectional area of whole mutant tendons was also significantly less than that of the wild-type tendons causing joint laxity and stiffness, easy tiring and weakness. This study is important because those diseases are often mistaken for neurological problems, since the doctor can detect a muscle weakness. This includes many painful and useless clinical neurological examination before the correct diagnosis. In this work, the researchers suggest to the pediatric doctor to perform x-rays before starting the neurological assessment, to exclude the dysplasia.[31]
COL9A1 mutation was discovered in 2001.[32]
Culture
Prominent people with this condition
- Danny DeVito, American actor, producer, and director[33][34]
- Robert Reich,[35] former United States Secretary of Labor under President Bill Clinton from 1993 to 1997
- David Wetherill, British Paralympian table tennis athlete[36]
References
- S2CID 79825711.
- ISBN 978-88-299-1502-6.
- ^ S2CID 7728788.
- ^ "Multiple Epiphyseal Dysplasia (MED) – Pediatrics – Orthobullets".
- ^ "COL9A1 collagen type IX alpha 1 [ Homo sapiens (human) ]".
- ^ "COL9A2 collagen type IX alpha 2 [ Homo sapiens (human) ]".
- ^ "COL9A3 collagen type IX alpha 3".
- ^ "COMP cartilage oligomeric matrix protein [ Homo sapiens (human) ]".
- ^ "MATN3 matrilin 3 [ Homo sapiens (human) ]".
- from the original on May 3, 2014. Retrieved May 3, 2014.
- S2CID 37593399.
- PMID 7325960.
- ^ "GeneCards".
- PMID 21922596.
- ^ "MATN3 review".
- ^ "SLC26A2 solute carrier family 26".
- ^ Pagon RA, Bird TD, Dolan CR, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
- PMID 18498631.
- ISBN 978-0-7216-0378-0.)
{{cite book}}
: CS1 maint: multiple names: authors list (link - PMID 15887789. Archived from the original(PDF) on 2018-12-07. Retrieved 2009-02-15.
- ISBN 978-3-13-140561-6.
- PMID 19236692.
- ISBN 978-0-443-08650-2.
- ISBN 978-1-84882-610-6. Retrieved May 3, 2014.
- PMID 8279467.
- PMID 8307576.
- S2CID 43867448.
- PMID 7490089.
- PMID 12024046.
- PMID 17588960.
- PMID 19808781.
- PMID 11565064.
- ^ Jenkins, Mark (26 September 2013). "For Richer And For Poorer, But What Of That Vanishing Middle?". NPR. Retrieved 5 October 2015.
- ^ Joseph, Pat (2013-09-10). "Lights, Camera, Economics Robert Reich brings his message to the big screen". Berkeley. Retrieved 5 October 2015.
- ^ Leibovitch, Mark (March 14, 2002). "The True Measure of a Man". The Washington Post. Archived from the original on April 23, 2003. Retrieved November 8, 2008.
- ^ David Wetherill; Parasport Archived 2012-12-24 at archive.today