Autosomal recessive centronuclear myopathy

Alternate names

Myopathy, centronuclear, autosomal recessive; Myopathy, Centronuclear, 2; AR-CNM

Definition

Autosomal recessive centronuclear myopathy (AR-CNM) is a type of centronuclear myopathy, which is a group of rare, inherited conditions that affect the muscles.

Epidemiology

Centronuclear myopathy is a rare condition; its exact prevalence is unknown.

Cause

Most cases of AR-CNM are caused by changes (mutations) in the BIN1 gene; however, some affected families are reported to have mutations in the SPEG, TTN, or RYR1 genes.

Inheritance

Autosomal recessive inheritance, a 25% chance

The condition is inherited in an autosomal recessive manner.

Signs and symptoms

• In AR-CNM, specifically, affected people generally begin showing signs and symptoms during infancy or early childhood.
• The features of the condition can vary but may include progressive muscle weakness, foot abnormalities, high-arched palate, scoliosis, ptosis, mild to severe breathing problems, delayed motor milestones and cardiomyopathy (less commonly).

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

• Difficulty climbing stairs(Difficulty walking up stairs)
• Difficulty running
• Generalized amyotrophy(Diffuse skeletal muscle wasting)
• Generalized hypotonia(Decreased muscle tone)
• Gowers sign
• High palate(Elevated palate)
• Motor delay
• Progressive muscle weakness
• Respiratory insufficiency(Respiratory impairment)
• Retrognathia(Receding chin)
• Waddling gait('Waddling' gait)

5%-29% of people have these symptoms

• Abnormal heart valve morphology
• Areflexia(Absent tendon reflexes)
• Bifid uvula
• Centrally nucleated skeletal muscle fibers
• Delayed speech and language development(Deficiency of speech development)
• Dysarthria(Difficulty articulating speech)
• Dysphonia(Inability to produce voice sounds)
• EMG: decremental response of compound muscle action potential to repetitive nerve stimulation0003403
• Facial diplegia
• Hip contracture
• Hyperlordosis(Prominent swayback)
• Intellectual disability, mild(Mental retardation, borderline-mild)
• Left ventricular hypertrophy
• Long face(Elongation of face)
• Long fingers
• Narrow mouth(Small mouth)
• Ophthalmoplegia(Eye muscle paralysis)
• Pes cavus(High-arched foot)
• Protruding ear(Prominent ear)
• Respiratory insufficiency due to muscle weakness(Decreased lung function due to weak breathing muscles)
• Scapular winging(Winged shoulder blade)
• Talipes equinovarus(Club feet)
• Type 1 muscle fiber predominance

Diagnosis

Molecular Genetics Tests

• Deletion/duplication analysis
• Sequence analysis of the entire coding region
• Mutation scanning of the entire coding region
• Targeted variant analysis

Treatment

Treatment is based on the signs and symptoms present in each person and may include physical and/or occupational therapy and assistive devices to help with mobility, eating and/or breathing.

NIH genetic and rare disease info

• NIH info on Autosomal recessive centronuclear myopathy

Autosomal recessive centronuclear myopathy is a rare disease.