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Disease Profile

Distal myopathy with vocal cord weakness

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.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

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)

Distal myopathy 2; Myopathy, distal, 2; MPD2

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: 600

Definition
Vocal cord and pharyngeal distal myopathy (VCPDM) is a rare autosomal dominant distal myopathy characterized by adult onset of muscle weakness in the feet and hands (slowly progressing to involve proximal limb muscles) combined with vocal or swallowing dysfunction and frequent respiratory muscle involvement in later stages. Normal to mildly elevated creatine kinase (CK) serum levels and rimmed-vacuolated dystrophic muscle fiber changes are associated laboratory and pathologic findings.

Epidemiology
Worldwide prevalence is unknown but more than 70 patients (of North American, European, and Japanese origin) have been reported to date.

Clinical description
Onset of muscle weakness is between 30-63 years (mean in the forties) and may initially be asymmetric. It most frequently begins with involvement of ankle and toe extensors with foot drop or may manifest in the hands. Weakness in the ankles renders the gait very unstable resulting in a waddling and steppage gait. In the hands, the extensors of the fingers and the abductor pollicis brevis (with atrophy) are affected to varying degrees. Progression of muscle weakness and wasting to proximal upper and lower limb muscles is common. Bulbar involvement with dysphonia and dysphagia may be initially absent but appear as disease progresses. Initially, voice is usually nasal or hoarse and dysphagia mild (with difficulty swallowing solid food), but progressive vocal cord weakness eventually leads to aspiration. Some patients display respiratory impairment with a low vital capacity that may progress to respiratory failure. Ocular muscle involvement is not observed.

Etiology
VCPDM is caused by a c.254C>G mutation in the MATR3 gene (5q31.3) which results in substitution of a conserved amino acid (S85C) in the nuclear protein Matrin-3. It harbors nuclear import and export motifs in addition to several DNA and RNA binding sites. Currently, the mechanism by which S85C alteration in Matrin-3 leads to myopathy remains largely unknown.

Diagnostic methods
The diagnosis of VCPDM is clinical and involves vocal cord examination by laryngoscopy (which reveals bowing of the vocal cords and constantly flowing secretions, resulting from incomplete closure of the glottis and pharyngeal muscle weakness). Needle EMG shows myopathic changes. Muscle biopsies reveal chronic non-inflammatory myopathy with variations in fiber size, fiber splitting and subsarcolemmal rimmed vacuoles, with pathologic changes being scant in the quadriceps and severe in the gastrocnemius. CK serum levels range from normal to an 8 fold increase. Molecular genetic screening revealing mutation in the MATR3 gene confirms diagnosis.

Differential diagnosis
Differential diagnosis includes Welander distal myopathy, oculopharyngeal muscular dystrophy, and oculopharyngodistal myopathy.

Genetic counseling
VCPDM is inherited in an autosomal dominant manner. Genetic counseling can inform affected individuals about the 50% risk of disease transmission to their offspring.

Management and treatment
Currently, there is no cure for VCPDM. Ankle-foot orthotic braces and/or canes are used to aid in ambulation. For patients suffering from vocal cord weakness, injection of agents that add bulk and act as stiffeners (teflon, gel foam, fat), or bilateral silastic-implant medialization of the vocal folds, may aid in reducing aspiration. Ventilation or oxygen therapy may be needed if patient presents severe respiratory muscle involvement.

Prognosis
Prognosis of patients suffering from vocal cord and pharyngeal weakness is highly influenced by the quality of long-term respiratory care, if it is needed. Moreover, as distal upper limb muscles weaken, hand may partially curl closed, leading to a general loss of grip and dexterity. Ambulation is usually preserved.

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
30%-79% of people have these symptoms
Abnormal morphology of musculature of pharynx
0430015
Abnormality of the calf musculature
Abnormal calf muscles
0001430
Amyotrophic lateral sclerosis
0007354
Ankle weakness
0031374
Aspiration
0002835
Bowing of the vocal cords
0008756
Bulbar palsy
0001283
Difficulty walking
Difficulty in walking
0002355
Distal muscle weakness
Weakness of outermost muscles
0002460
Dysarthria
Difficulty articulating speech
0001260
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
EMG abnormality
0003457
Exercise-induced myalgia
Exercise-induced muscle pain
Muscle pain on exercise
Muscle pain with exercise
Muscle pain, exercise-induced

[ more ]

0003738
Hoarse voice
Hoarseness
Husky voice

[ more ]

0001609
Hyperreflexia
Increased reflexes
0001347
Imperfect vocal cord adduction
0005934
Mildly elevated creatine kinase
0008180
Nasal speech
Nasal voice
0001611
Respiratory insufficiency due to muscle weakness
Decreased lung function due to weak breathing muscles
0002747
Rimmed vacuoles
0003805
Unsteady gait
Unsteady walk
0002317
Vocal cord paresis
Weakness of the vocal cords
0001604
Weak voice
Soft voice
0001621
5%-29% of people have these symptoms
Abnormality of the extraocular muscles
0008049
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
Distal sensory impairment
Decreased sensation in extremities
0002936
Distal upper limb amyotrophy
0007149
Shoulder girdle muscle weakness
Weak shoulder muscles
0003547
1%-4% of people have these symptoms
Decreased nerve conduction velocity
0000762
Percent of people who have these symptoms is not available through HPO
Abnormal lower motor neuron morphology
0002366
Abnormal nasopharynx morphology
0001739
Abnormal upper motor neuron morphology
Abnormal shape of upper motor neuron
0002127
Adult onset
Symptoms begin in adulthood
0003581
Autosomal dominant inheritance
0000006
Bulbar signs
0002483
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase

[ more ]

0003236
Variable expressivity
0003828

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

  • Genetics Home Reference (GHR) contains information on Distal myopathy with vocal cord weakness. This website is maintained by the National Library of Medicine.
  • 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.