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Distal nebulin myopathy
Distal nebulin myopathy is a rare, slowly progressive, autosomal recessive distal myopathy characterized by early onset of predominantly distal muscle weakness and atrophy affecting lower leg extensor muscles, finger extensors and neck flexors. Muscle histology does not always show nemaline rods.
ORPHA:399103Classification level: Disorder
- Nebulin-related early-onset distal myopathy
- Prevalence: <1 / 1 000 000
- Inheritance: -
- Age of onset: Infancy, Adolescent, Childhood, Adult
- ICD-10: G71.0
- OMIM: -
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
To date, the disease has been described in 13 patients from five unrelated Finnish families and four non-Finnish families.
Distal nebulin myopathy manifests initially, in early childhood or young adulthood, by foot drop, but the first symptoms can be seen as early as one year of age. The most severely affected muscles include the ankle dorsiflexors, the finger extensors and the neck flexors. Patients are usually not able to walk on their heels and later in the disease course, there is a mild proximal muscle involvement. Additional features include early-onset moderate facial weakness and mild respiratory problems, such as shortness of breath on strenuous exercise (although only one patient presenting decreased vital capacity has been reported). Cardiac muscle is usually not affected, however cardiomyopathy has been described in one patient.
Distal nebulin myopathy is caused by biallelic mutations (with at least one of them being missense mutation) in the gene NEB (2q22) which encodes the protein nebulin. The latter is expressed in the thin filaments of striated muscle and is required for the proper assembly of the thin filaments, for the maintenance of their lengths and for their contractile function.
Diagnosis is based on clinical, muscle histology and laboratory examinations. Muscle histology shows a marked fiber size variation, presence of hypertrophic fibers with internal nuclei, and variably abundant nemaline rods. CK levels are normal or slightly increased. Diagnosis is confirmed by genetic screening of NEB.
Differential diagnosis includes other distal myopathies, especially Laing distal myopathy.
Transmission is autosomal recessive and genetic counseling is recommended for at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% chance of having an affected child.
Management and treatment
Currently no specific treatment is available. Management is mainly symptomatic and includes the help of an occupational and a physical therapists. Foot drop may be aided by orthoses. Occasional monitoring of respiratory function is recommended.
Prognosis is good with patients typically remaining ambulant although proximal weakness may occur at the later stages.