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Disease Profile

Welander distal myopathy, Swedish type

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Adult

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ICD-10

G71.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Welander distal myopathy; WDM; Distal myopathy, Swedish type

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 603

Definition
A rare distal myopathy characterized by weakness in the distal upper extremities, usually finger and wrist extensors which later progresses to all hand muscles and distal lower extremity, primarily in toe and ankle extensors.

Epidemiology
Distal myopathy, Welander type (WDM) prevalence is unknown. The condition is mainly restricted to a geographical area around the Baltic Sea especially in Finland and Sweden (mid-eastern region), where the estimated prevalence is 1/10,000. However, some patients have been reported in the United Kingdom.

Clinical description
WDM is a late adult-onset disorder (onset between 40 and 60 years) characterized by initial weakness of index finger extensors followed by extension weakness in the other fingers. Weakness slowly progresses to all hand and lower leg muscles. In the lower limb, the anterior tibial muscle and toe extensors are typically affected leading to walking difficulties and steppage gait. Proximal limb muscles are only rarely involved. Muscle stretch reflexes are preserved (except ankle reflexes which may be lost later in the disease). Cardiac muscle involvement has not been observed. Rare homozygotes individuals show an earlier onset and proximal muscle involvement with faster progression.

Etiology
WDM is caused by a missense change (c.1362G>A; p.E384K) in TIA1 gene (2p13) which encodes nucleolysin TIA1 isoform p40, a key component of stress granules (SGs). Under conditions of cellular stress or metabolic changes, nucleolysin TIA1 isoform p40 promotes messenger ribonucleoprotein (mRNP) complexes to assemble in SGs to repress translation. The mutation leads to reduced dynamics of the SGs and abnormal autophagic processing with rimmed vacuolar pathology. In addition, the WDM phenotype has been reported in patients with a digenic combination of a SQSTM1 mutation and TIA1-N357S variant.

Diagnostic methods
Diagnosis relies on molecular genetic testing. Additional examinations include muscle biopsy of distal muscles showing dystrophic features and prominent rimmed vacuoles. Sensory examination is usually normal, although some deficits on quantitative temperature and vibration testing have been described. The serum creatine kinase (CK) level is usually normal or slightly elevated. Needle electromyography (EMG) shows small brief 'myopathic' motor units, although a mixed 'myopathic-neuropathic' pattern may be observed. Fibrillations and complex repetitive discharges are often, but not invariably, present. Muscle magnetic resonance imaging shows considerable involvement of posterior calf muscles besides fatty degenerative changes in the anterior compartment.

Differential diagnosis
Differential diagnosis includes sporadic inclusion body myositis (sIBM), MATR3 distal myopathy, and muscle filaminopathy.

Genetic counseling
WDM is inherited as an autosomal dominant trait. Where one parent is affected, there is a 50% risk of disease transmission to offspring. Penetrance is 100% by age 75 years.

Management and treatment
Management is mainly symptomatic and includes the help of an occupational and a physical therapists and practical tools for finger and hand weakness. Foot drop and wrist weakness may be helped by orthoses.

Prognosis
The progression is benign and life expectancy is normal although the fine motor hand skills are usually lost. Homozygotes exhibit earlier onset, faster progression, and patients become wheelchair-bound by the age of 50 years.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Distal upper limb muscle weakness
0008959
EMG: myopathic abnormalities
0003458
Foot dorsiflexor weakness
Foot drop
0009027
Intrinsic hand muscle atrophy
0008954
Weakness of long finger extensor muscles
0009077
30%-79% of people have these symptoms
Clumsiness
0002312
Difficulty walking
Difficulty in walking
0002355
Mildly elevated creatine kinase
0008180
Rimmed vacuoles
0003805
Steppage gait
High stepping
0003376
Percent of people who have these symptoms is not available through HPO
Adult onset
Symptoms begin in adulthood
0003581
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Distal amyotrophy
Distal muscle wasting
0003693
Distal muscle weakness
Weakness of outermost muscles
0002460
Slow progression
Signs and symptoms worsen slowly with time
0003677

Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

  • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The Muscular Dystrophy Association has developed a resource called "Facts About Myopathies" that discusses commonly asked questions regarding myopathies. Click on the link above to view this information page.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Welander distal myopathy, Swedish type. Click on the link to view a sample search on this topic.