Congenital fiber type disproportion

Alternate names

Congenital fiber-type disproportion myopathy; Myopathy, congenital with fiber-type disproportion; CFTDM; Fiber-type disproportion myopathy, congenital

Definition

Congenital fiber type disproportion is a type of congenital myopathy. Congenital myopathy refers to a group of muscle disorders that appear at birth or in infancy.

Histopathology of congental muscle fibre dysproportion showing predominance of type 1 fibres which appear to be atrophic (yellow arrows) and few type 2 fibres. ATPase staining (pH 4) of a muscle biopsy.

Epidemiology

Congenital fiber-type disproportion is thought to be a rare condition, although its prevalence is unknown.

Cause

• Mutations in multiple genes can cause congenital fiber-type disproportion.
• Mutations in the TPM3, RYR1 and ACTA1 genes cause 35 to 50 percent of cases, while mutations in other genes, some known and some unidentified, are responsible for the remaining cases.
• The genes that cause congenital fiber-type disproportion provide instructions for making proteins that are involved in the tensing of muscle fibers (muscle contraction).
• Changes in these proteins lead to impaired muscle contraction, resulting in muscle weakness.
• Skeletal muscle is made up of two types of muscle fibers: type I (slow twitch fibers) and type II (fast twitch fibers).
• Normally, type I and type II fibers are the same size.
• In people with congenital fiber-type disproportion, type I skeletal muscle fibers are significantly smaller than type II skeletal muscle fibers.
• It is unclear whether the small type I skeletal muscle fibers lead to muscle weakness or are caused by muscle weakness in people with congenital fiber-type disproportion.

Inheritance

• Congenital fiber-type disproportion can have multiple inheritance patterns.
• When this condition is caused by mutations in the ACTA1 gene, it usually occurs in an autosomal dominant pattern. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder.
• Most other cases of congenital fiber-type disproportion, including those caused by mutations in the RYR1 gene, have an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
• When this condition is caused by mutations in the TPM3 gene, it can occur in either an autosomal dominant or autosomal recessive pattern.
• In rare cases, this condition can be inherited in an X-linked pattern, although the gene or genes associated with X-linked congenital fiber-type disproportion have not been identified.
• A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males or may cause no symptoms at all.
• A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
• It is estimated that 40 percent of individuals with congenital fiber-type disproportion have an affected relative.

Signs and symptoms

Early signs and symptoms of congenital fiber type disproportion include floppiness, limb and facial weakness, and breathing problems.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Generalized muscle weakness
• Muscular hypotonia(Low or weak muscle tone)
• Reduced tendon reflexes

30%-79% of people have these symptoms

• Ankle flexion contracture
• Decreased fetal movement(Less than 10 fetal movements in 12 hours)
• EMG: myopathic abnormalities
• Failure to thrive(Faltering weight)
• Fatigable weakness of bulbar muscles
• High palate(Elevated palate)
• Hip contracture
• Joint laxity(Joint instability)
• Long face(Elongation of face)
• Mildly elevated creatine kinase
• Motor delay
• Pectus excavatum(Funnel chest)
• Poor suck(Poor sucking)
• Recurrent respiratory infections(Frequent respiratory infections)
• Reduced vital capacity
• Respiratory insufficiency due to muscle weakness(Decreased lung function due to weak breathing muscles)
• Tented upper lip vermilion
• Type 1 muscle fiber atrophy
• Waddling gait('Waddling' gait)
• Weak cry

5%-29% of people have these symptoms

• Calf muscle hypertrophy(Increased size of calf muscles)
• Congenital hip dislocation(Dislocated hip since birth)
• Elbow flexion contracture(Contractures of elbows)
• Flexion contracture of finger
• Hyperlordosis(Prominent swayback)
• Knee flexion contracture
• Kyphoscoliosis
• Micrognathia(Little lower jaw)
• Ophthalmoplegia(Eye muscle paralysis)
• Polyhydramnios(High levels of amniotic fluid)
• Ptosis(Drooping upper eyelid)
• Pulmonary hypoplasia(Small lung)
• Scapular winging(Winged shoulder blade)
• Short stature(Decreased body height)
• Talipes equinovarus(Club feet)

1%-4% of people have these symptoms

• Cryptorchidism(Undescended testes)
• Dilated cardiomyopathy(Stretched and thinned heart muscle)
• Intellectual disability(Mental deficiency)
• Limb joint contracture(Limb contractures)
• Scoliosis

Diagnosis

• Diagnosis is based on a combination of clinical presentation and morphologic features observed on skeletal muscle histology.
• The pathologic and clinical manifestations of CFTD overlap with other neuromuscular and non-neuromuscular diseases that must be ruled out prior to making a diagnosis of CFTD.

Treatment

• Currently we are not aware of new therpies, drugs, supplements, or vitamins to cure or effectively treat congenital fiber-type disproportion.
• Supportive treatment may involve orthopedic treatments, as well as physical, occupational or speech therapy.

NIH genetic and rare disease info

• NIH info on Congenital fiber type disproportion

Congenital fiber type disproportion is a rare disease.

Congenital fiber type disproportion Resources
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