Distal myopathy with vocal cord weakness

Alternate names

Distal myopathy 2; Myopathy, distal, 2; MPD2

Definition

Distal myopathy 2 is a condition characterized by weakness of specific muscles that begins in adulthood. It is a form of muscular dystrophy that specifically involves muscles in the throat, lower legs, and forearms.

Epidemiology

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

Cause

• A mutation in the MATR3 gene has been identified in people with distal myopathy 2.
• This gene provides instructions for making a protein called matrin 3, which is found in the nucleus of the cell as part of the nuclear matrix. The nuclear matrix is a network of proteins that provides structural support for the nucleus and aids in several important nuclear functions.
• The function of the matrin 3 protein is unknown.
• This protein can attach to (bind) RNA, which is a chemical cousin of DNA.
• Some studies indicate that matrin 3 binds and stabilizes a type of RNA called messenger RNA (mRNA), which provides the genetic blueprint for proteins. Matrin 3 may also bind certain abnormal RNAs that might lead to nonfunctional or harmful proteins, thereby blocking the formation of such proteins.
• Other studies suggest that the matrin 3 protein may be involved in cell survival.

Gene mutations

• The MATR3 gene mutation identified in people with distal myopathy 2 changes a single protein building block (amino acid) in the matrin 3 protein.
• The effect of this mutation on the function of the protein is unknown, although one study suggests that the mutation may change the location of the protein in the nucleus.
• Researchers are working to determine how this gene mutation leads to the signs and symptoms of distal myopathy 2.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Distal myopathy 2 is inherited in an autosomal dominant pattern, which means one copy of the altered MATR3 gene in each cell is sufficient to cause the disorder.

Onset

Onset of muscle weakness is between 30-63 years (mean in the forties) and may initially be asymmetric.

Signs and symptoms

• 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.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

30%-79% of people have these symptoms

• Abnormal morphology of musculature of pharynx
• Abnormality of the calf musculature(Abnormal calf muscles)
• Amyotrophic lateral sclerosis
• Ankle weakness
• Aspiration
• Bowing of the vocal cords
• Bulbar palsy
• Difficulty walking(Difficulty in walking)
• Distal muscle weakness(Weakness of outermost muscles)
• Dysarthria(Difficulty articulating speech)
• Dysphagia(Poor swallowing)
• EMG abnormality
• Exercise-induced myalgia(Exercise-induced muscle pain)
• Hoarse voice(Hoarseness)
• Hyperreflexia(Increased reflexes)
• Imperfect vocal cord adduction
• Mildly elevated creatine kinase
• Nasal speech(Nasal voice)
• Respiratory insufficiency due to muscle weakness(Decreased lung function due to weak breathing muscles)
• Rimmed vacuoles
• Unsteady gait(Unsteady walk)
• Vocal cord paresis(Weakness of the vocal cords)
• Weak voice(Soft voice)

5%-29% of people have these symptoms

• Abnormality of the extraocular muscles
• Dementia(Dementia, progressive)
• Distal sensory impairment(Decreased sensation in extremities)
• Distal upper limb amyotrophy
• Shoulder girdle muscle weakness(Weak shoulder muscles)

1%-4% of people have these symptoms

• Decreased nerve conduction velocity

Diagnosis

• 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.

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.

NIH genetic and rare disease info

• NIH info on Distal myopathy with vocal cord weakness

Distal myopathy with vocal cord weakness is a rare disease.

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