Orthopaedic Disorders in Myotonic Dystrophy

NewsBot · Dec 3, 2013

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Orthopaedic Disorders in Myotonic Dystrophy Type 1: descriptive clinical study of 21 patients.
Schilling L, Forst R, Forst J, Fujak A.
BMC Musculoskelet Disord. 2013 Dec 1;14(1):338.

BACKGROUND:
Myotonic Dystrophy Type 1 (DM1) is the most common form of hereditary myopathy presenting in adults. This autosomal-dominant systemic disorder is caused by a CTG repeat, demonstrating various symptoms. A mild, classic and congenital form can be distinguished. Often the quality of life is reduced by orthopaedic problems, such as muscle weakness, contractures, foot or spinal deformities, which limit patients' mobility.The aim of our study was to gather information about the orthopaedic impairments in patients with DM1 in order to improve the medical care of patients, affected by this rare disease.
METHODS:
A retrospective clinical study was carried out including 21 patients (11 male and 10 female), all diagnosed with DM1 by genetic testing. All patients were seen during our special consultations for neuromuscular diseases, during which patients were interviewed and examined. We also reviewed surgery reports of our hospitalized patients.
RESULTS:
We observed several orthopaedic impairments: spinal deformities (scoliosis, hyperkyphosis, rigid spine), contractures (of the upper extremities and the lower extremities), foot deformities (equinus deformity, club foot, pes cavus, pes planovalgus, pes cavovarus, claw toes) and fractures.Five patients were affected by pulmonary diseases (obstructive airway diseases, restrictive lung dysfunctions). Twelve patients were affected by cardiac disorders (congenital heart defects, valvular heart defects, conduction disturbances, pulmonary hypertension, cardiomyopathy).Our patients received conservative therapy (physiotherapy, logopaedic therapy, ergotherapy) and we prescribed orthopaedic technical devices (orthopaedic custom-made shoes, insoles, lower and upper leg orthoses, wheelchair, Rehab Buggy). We performed surgery for spinal and foot deformities: the scoliosis of one patient was stabilized and seven patients underwent surgery for correction of foot deformities.
CONCLUSIONS:
An orthopaedic involvement in DM1 patients should not be underestimated. The most common orthopaedic impairments are contractures, foot deformities and spinal deformities. Contractures are typically located distally in the lower extremities, but can also occur in the hip or shoulder joints. Foot deformities could be treated with orthopaedic custom-made shoes, orthoses or insoles. Surgery is indicated for severe foot deformities or contractures.
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Admin2 · Dec 3, 2013

Myotonic dystrophy

Genetic disorder that impairs muscle function

Medical condition

Myotonic dystrophy (DM) is a type of muscular dystrophy, a group of genetic disorders that cause progressive muscle loss and weakness.^[1] In DM, muscles are often unable to relax after contraction.^[1] Other manifestations may include cataracts, intellectual disability and heart conduction problems.^[1]^[2] In men, there may be early balding and an inability to father children.^[1] While myotonic dystrophy can occur at any age, onset is typically in the 20s and 30s.^[1]
Myotonic dystrophy is caused by a genetic mutation in one of two genes. Mutation of the DMPK gene causes myotonic dystrophy type 1 (DM1). Mutation of CNBP gene causes type 2 (DM2).^[1] DM is typically inherited, following an autosomal dominant inheritance pattern,^[1] and it generally worsens with each generation.^[1] A type of DM1 may be apparent at birth.^[1] DM2 is generally milder.^[1] Diagnosis is confirmed by genetic testing.^[2]
There is no cure.^[3] Treatments may include braces or wheelchairs, pacemakers and non-invasive positive pressure ventilation.^[2] The medications mexiletine or carbamazepine can help relax muscles.^[2] Pain, if it occurs, may be treated with tricyclic antidepressants and nonsteroidal anti-inflammatory drugs (NSAIDs).^[2]
Myotonic dystrophy affects about 1 in 2,100 people,^[4] a number that was long estimated to be much lower (often cited as 1 in 8,000), reflecting that not all patients have immediate symptoms and, once they do have symptoms, the long time it typically takes to get to the right diagnosis.^[1] It is the most common form of muscular dystrophy that begins in adulthood.^[1] It was first described in 1909, with the underlying cause of type 1 determined in 1992.^[2]

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v "myotonic dystrophy". GHR. 11 October 2016. Archived from the original on 18 October 2016. Retrieved 16 October 2016.

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j Meola, G; Cardani, R (April 2015). "Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and molecular pathomechanisms". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1852 (4): 594–606. doi:10.1016/j.bbadis.2014.05.019. PMID 24882752.

^ Klein, AF; Dastidar, S; Furling, D; Chuah, MK (2015). "Therapeutic Approaches for Dominant Muscle Diseases: Highlight on Myotonic Dystrophy". Current Gene Therapy. 15 (4): 329–37. doi:10.2174/1566523215666150630120537. PMID 26122101.

^ Johnson, N. (2021). "Population-Based Prevalence of Myotonic Dystrophy Type 1 Using Genetic Analysis of Statewide Blood Screening Program". Neurology. 96 (7): e1045–e1053. doi:10.1212/WNL.0000000000011425. PMC 8055332. PMID 33472919.

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NewsBot · Jan 2, 2014

Press release:
Scripps Florida Scientists Uncover Most Detailed Picture Yet of Muscular Dystrophy Defect then Design Targeted New Drug Candidates

JUPITER, FL, January 2, 2014 – Scientists from the Florida campus of The Scripps Research Institute have revealed an atomic-level view of a genetic defect that causes a form of muscular dystrophy, myotonic dystrophy type 2, and have used this information to design drug candidates with potential to counter those defects—and reverse the disease.

“This the first time the structure of the RNA defect that causes this disease has been determined,” said TSRI Associate Professor Matthew Disney, who led the study. “Based on these results, we designed compounds that, even in small amounts, significantly improve disease-associated defects in treated cells.”

Myotonic dystrophy type 2 is a relatively rare form of muscular dystrophy that is somewhat milder than myotonic dystrophy type 1, the most common adult-onset form of the disease.

Both types of myotonic dystrophy are inherited disorders that involve progressive muscle wasting and weakness, and both are caused by a type of genetic defect known as a “RNA repeat expansion,” a series of nucleotides repeated more times than normal in an individual’s genetic code. The repeat binds to the protein MBNL1, rendering it inactive and resulting in RNA splicing abnormalities—which lead to the disease.

Many other researchers had tried to find the atomic-level structure of the myotonic dystrophy 2 repeat, but had run into technical difficulties. In a technique called X-ray crystallography, which is used to find detailed structural information, scientists manipulate a molecule so that a crystal forms. This crystal is then placed in a beam of X-rays, which diffract when they strike the atoms in the crystal. Based on the pattern of diffraction, scientists can then reconstruct the shape of the original molecule.

Prior to the new research, which was published in an advance, online issue of the journal ACS Chemical Biology, scientists had not been able to crystallize the problematic RNA. The Scripps Florida team spent several years on the problem and succeeded in engineering the RNA to have crystal contacts in different positions. This allowed the RNA to be crystallized—and its structure to be revealed.

Using information about the RNA’s structure and movement, the scientists were able to design molecules to improve RNA function.

The new findings were confirmed using sophisticated computational models that show precisely how the small molecules interact with and alter the RNA structure over time. Those predictive models matched what the scientists found in the study—that these new compounds bind to the repeat structure in a predictable and easily reproducible way, attacking the cause of the disease.

“We used a bottom-up approach, by first understanding how the small components of the RNA structure interact with small molecules,” said Jessica Childs-Disney of TSRI, who was first author of the paper with Ilyas Yildirim of Northwestern University. “The fact that our compounds improve the defects shows that our unconventional approach works.”

In addition to Disney, Childs-Disney and Yildirim authors of the study, “Myotonic Dystrophy Type 2 RNA: Structural Studies and Designed Small Molecules that Modulate RNA Function,” include Jeremy Lohman, Lirui Guan, Tuan Tran, and HaJeung Park of TSRI; Partha Sarkar of the University of Texas Medical Branch and George C. Schatz of Northwestern University. For more information on the study, see http://pubs.acs.org/doi/abs/10.1021/cb4007387
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NewsBot · Nov 2, 2018

Ankle Strength Impairments in Myotonic Dystrophy Type 1: A Five-Year Follow-up.
Hébert LJ et al
J Neuromuscul Dis. 2018;5(3):321-330. doi: 10.3233/JND-180311.

BACKGROUND:
In Myotonic Dystrophy type 1 (DM1) patients, ankle muscles are affected early and this impairment is reported to be a good biological marker for longitudinal studies.

OBJECTIVE:
To characterize the ankle dorsiflexion (DF) and eversion (EV) maximal isometric muscle strength changes in adult DM1 patients over 5 years using a standardized handheld dynamometer protocol and the Myoankle method, compare the changes measured with both methods and to the standard error of measurement, and verify the relationship between ankle muscle strength and gait performance.

METHODS:
The maximal isometric muscle strength of ankle DF and EV in DM1 patients from Quebec and Lyon was assessed at baseline, 18, 36 and 60 months using a handheld dynamometer (HHD) protocol and the MyoAnkle method.

RESULTS:
There was a decrease of torque in DF/EV of 36.0% /31.3% and 27.7% /35.5% for the Quebec and Lyon cohorts respectively (p≤0.01), but not in a linear way. In most cases (82.5%), the changes observed were greater than the standard error of measurement. DF torque measures taken by the two methods (HHD and MyoAnkle) were highly correlated (rp = 0.97-0.98, p < 0.001).

CONCLUSION:
Muscle strength ankle impairments are clinically meaningful in DM1 and can be accurately monitored using quantitative testing to measure the efficacy of therapeutic trials.
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Orthopaedic Disorders in Myotonic Dystrophy

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Myotonic dystrophy

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NewsBot The Admin that posts the news.

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Orthopaedic Disorders in Myotonic Dystrophy

NewsBot The Admin that posts the news.

Admin2 Administrator Staff Member

Myotonic dystrophy

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

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