Distal myopathy

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Distal myopathy
Other namesDistal muscular dystrophy
Body Diagram.png
Red depicts the preferentially affected areas in distal myopathy.
Specialty Neurology, neuromuscular medicine
Symptoms Weakness of hands and/or feet
Complications Cardiomyopathy
Usual onsetVariable
TypesClassic, myofibrillar myopathy, other
CausesGenetic mutation of various genes
Diagnostic method Genetic testing, muscle biopsy

Distal myopathy is a group of rare genetic disorders that cause muscle damage and weakness, predominantly in the hands and/or feet. Mutation of many different genes can be causative. Many types involve dysferlin. [1]


Signs and symptoms

All of the different types affect different regions of the extremities and can show up as early as 5 years of age to as late as 50 years old. Distal myopathy has slow progress therefore the patient may not know that they have it until they are in their late 40s or 50s.[ citation needed ]

Miyoshi myopathy affects the posterior muscles of the lower leg, more so than the anterior muscles of the lower leg. [2] [3]


DYSF 4ihb pdb.png

The cause of this myopathy is very hard to determine because it can be a mutation in any of at least eight genes and not all are known yet. These mutations can be inherited from one parent, autosomal dominant, or from both parents, autosomal recessive. There are eight known types of distal myopathy.[ citation needed ]


Classic distal muscular dystrophies
TypeEponymInheritance OMIM GeneLocusGene also implicated in:
Late adult-onset type 1 [4] WelanderAD [5] 604454 TIA1 [6] 2p13 [7]
Late adult-onset type 2a [5] - Finnish (tibial)UddAD [5] 600334 TTN [5] 2q31.2
Late adult-onset type 2b [5] Markesbery–GriggsAD [8] ZASP [5] 10q23.2
Early adult-onset type 1 [4] NonakaAR [5] 605820 GNE [5] 9p13.3
Early adult-onset type 2 [4] MiyoshiAR [5] 254130 DYSF [5] 2p13.3-p13.1 limb-girdle muscular dystrophy type 2B. [9]
Distal myopathy with anterior tibial onset (DMAT) [10] [11] 606768 DMAT can be considered a variant of Miyoshi.
Early adult-onset type 3 [4] Laing (Gower)AD [5] 160500 MYH7 [5] 14q11.2
AD = autosomal dominant; AR = autosomal recessive
Myofibrillar myopathies classifiable as distal myopathy
TypeEponymInheritance OMIM GeneLocusGene also implicated in:
Desmin — adult onset (MFM1) [5]

Hereditary inclusion-body myositis type 1 [5]

αB-crystallin — early - mid adult (MFM2) [5] AD
ZASP— late adult (MFM4) [5] AD
Scapuloperoneal [5] AD
MFM = myofibrillary myopathy; AD = autosomal dominant; AR = autosomal recessive
Other distal muscular dystrophies
TypeEponymInheritance OMIM GeneLocusGene also implicated in:
Distal myopathy with vocal cord and pharyngeal weakness [4] AD [5] 606070 MATR3 [5] 5q31 [5] Amyotrophic lateral sclerosis 21 (ALS21). One study suggests that all cases are ALS, justifying reclassification. [12]


In terms of diagnosis, Vocal cord and pharyngeal distal myopathy should be assessed via serum CK levels, as well as muscle biopsy of the individual suspected of being afflicted with this condition [13]


As of 2011, no disease modifying treatments are known. [8] Foot drop can be managed with ankle-foot orthoses or surgical tendon transfer, [8] in which the tibialis posterior muscle is repurposed to function as a tibialis anterior muscle. In select types of distal myopathy, evaluation of the heart may be indicated. [8] Scoliosis and contractures can be surgically managed. [8]

Related Research Articles

Muscular dystrophy Genetic disorder

Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affected, the degree of weakness, how fast they worsen, and when symptoms begin. Some types are also associated with problems in other organs.

Limb–girdle muscular dystrophy Medical condition

Limb–girdle muscular dystrophy (LGMD) is a genetically heterogeneous group of rare muscular dystrophies that share a set of clinical characteristics. It is characterised by progressive muscle wasting which affects predominantly hip and shoulder muscles. LGMD usually has an autosomal pattern of inheritance. It currently has no known cure or treatment.

Myotonia is a symptom of a small handful of certain neuromuscular disorders characterized by delayed relaxation of the skeletal muscles after voluntary contraction or electrical stimulation.

Spinal muscular atrophies Group of disorders

Spinal muscular atrophies (SMAs) are a genetically and clinically heterogeneous group of rare debilitating disorders characterised by the degeneration of lower motor neurons and subsequent atrophy (wasting) of various muscle groups in the body. While some SMAs lead to early infant death, other diseases of this group permit normal adult life with only mild weakness.

Dystrophin Rod-shaped cytoplasmic protein

Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex (DAPC). Many muscle proteins, such as α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan, colocalize with dystrophin at the costamere. It has a molecular weight of 427 kDa

Nemaline myopathy is a congenital, often hereditary neuromuscular disorder with many symptoms that can occur such as muscle weakness, hypoventilation, swallowing dysfunction, and impaired speech ability. The severity of these symptoms varies and can change throughout one's life to some extent. The prevalence is estimated at 1 in 50,000 live births. It is the most common non-dystrophic myopathy.

Facioscapulohumeral muscular dystrophy Medical condition

Facioscapulohumeral muscular dystrophy (FSHD) is a type of muscular dystrophy, a group of heritable diseases that cause degeneration of muscle and progressive weakness. Per the name, FSHD tends to sequentially weaken the muscles of the face, those that position the scapula, and those overlying the humerus bone of the upper arm. These areas can be spared, and muscles of other areas usually are affected, especially those of the chest, spine, abdomen, and shin. Almost any skeletal muscle can be affected in severe disease. Abnormally positioned, or winged, scapulas are common, as is the inability to lift the foot, known as foot drop. The two sides of the body are often affected unequally. Weakness typically manifests at ages 15 – 30 years. FSHD can also cause hearing loss and blood vessel abnormalities in the back of the eye.

Dysferlin Protein encoded by the DYSF gene in humans

Dysferlin also known as dystrophy-associated fer-1-like protein is a protein that in humans is encoded by the DYSF gene.

Zaspopathy Medical condition

Zaspopathy, also called ZASP-related myofibril myopathy, is a novel autosomal dominant form of progressive muscular dystrophy, first described in 2005.

Neuromuscular disease Medical condition

A neuromuscular disease is any disease affecting the peripheral nervous system (PNS), the neuromuscular junction, or skeletal muscle, all of which are components of the motor unit. Damage to any of these structures can cause muscle atrophy and weakness. Issues with sensation can also occur.

Congenital muscular dystrophy Medical condition

Congenital muscular dystrophies are autosomal recessively-inherited muscle diseases. They are a group of heterogeneous disorders characterized by muscle weakness which is present at birth and the different changes on muscle biopsy that ranges from myopathic to overtly dystrophic due to the age at which the biopsy takes place.

Caveolin 3

Caveolin-3 is a protein that in humans is encoded by the CAV3 gene. Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites.

The dystrophin-associated protein complex, also known as the dystrophin-associated glycoprotein complex is a multiprotein complex that includes dystrophin and the dystrophin-associated proteins. It is one of the two protein complexes that make up the costamere in striated muscle cells. The other complex is the integrin-vinculin-talin complex.


Myotilin is a protein that in humans is encoded by the MYOT gene. Myotilin also known as TTID is a muscle protein that is found within the Z-disc of sarcomeres.

Ullrich congenital muscular dystrophy Medical condition

Ullrich congenital muscular dystrophy is a form of congenital muscular dystrophy. It is associated with variants of type VI collagen, it is commonly associated with muscle weakness and respiratory problems, though cardiac issues are not associated with this type of CMD. It is named after Otto Ullrich, who is also known for the Ullrich-Turner syndrome.


Anoctamin 5 (ANO5) is a protein that in humans is encoded by the ANO5 gene.

Ferlins Protein family

Ferlins are an ancient protein family involved in vesicle fusion and membrane trafficking. Ferlins are distinguished by their multiple tandem C2 domains, and sometimes a FerA and a DysF domain. Mutations in ferlins can cause human diseases such as muscular dystrophy and deafness. Abnormalities in expression of myoferlin, a human ferlin protein, is also directly associated with higher mortality rate and tumor recurrence in several types of cancer, including pancreatic, colorectal, breast, cervical, stomach, ovarian, cervical, thyroid, endometrial, and oropharyngeal squamous cell carcinoma. In other animals, ferlin mutations can cause infertility.

Muscle–eye–brain disease Medical condition

Muscle–eye–brain (MEB) disease, also known as muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A3 (MDDGA3), is a kind of rare congenital muscular dystrophy (CMD), largely characterized by hypotonia at birth. Patients have muscular dystrophy, central nervous system abnormalities and ocular abnormalities. The condition is degenerative.

Lisa Welander Swedish neurologist

Lisa Welander was a Swedish neurologist, and was Sweden's first professor of neurology, taking up her professorship at Umeå University from 1964–75.


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