Cap myopathy

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Cap myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with cap myopathy have muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body, but they are most severely affected in the muscles of the face, neck, and limbs. The muscle weakness, which begins at birth or during childhood, can worsen over time.

Affected individuals may have feeding and swallowing difficulties in infancy. They typically have delayed development of motor skills such as sitting, crawling, standing, and walking. They may fall frequently, tire easily, and have difficulty running, climbing stairs, or jumping. In some cases, the muscles used for breathing are affected, and life-threatening breathing difficulties can occur.

People with cap myopathy may have a high arch in the roof of the mouth (high-arched palate), severely drooping eyelids (ptosis), and a long face. Some affected individuals develop an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis).

The name cap myopathy comes from characteristic abnormal cap-like structures that can be seen in muscle cells when muscle tissue is viewed under a microscope. The severity of cap myopathy is related to the percentage of muscle cells that have these caps. Individuals in whom 70 to 75 percent of muscle cells have caps typically have severe breathing problems and may not survive childhood, while those in whom 10 to 30 percent of muscle cells have caps have milder symptoms and can live into adulthood.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the ACTA1, TPM2, or TPM3 genes can cause cap myopathy. These genes provide instructions for producing proteins that play important roles in skeletal muscles.

The ACTA1 gene provides instructions for making a protein called skeletal alpha (α)-actin, which is part of the actin protein family. Actin proteins are important for cell movement and the tensing of muscle fibers (muscle contraction). Thin filaments made up of actin molecules and thick filaments made up of another protein called myosin are the primary components of muscle fibers and are important for muscle contraction. Attachment (binding) and release of the overlapping thick and thin filaments allows them to move relative to each other so that the muscles can contract. The mutation in the ACTA1 gene that causes cap myopathy results in an abnormal protein that may interfere with the proper assembly of thin filaments. The cap structures in muscle cells characteristic of this disorder are composed of disorganized thin filaments.

The TPM2 and TPM3 genes provide instructions for making proteins that are members of the tropomyosin protein family. Tropomyosin proteins regulate muscle contraction by attaching to actin and controlling its binding to myosin. The specific effects of TPM2 and TPM3 gene mutations are unclear, but researchers suggest they may interfere with normal actin-myosin binding between the thin and thick filaments, impairing muscle contraction and resulting in the muscle weakness that occurs in cap myopathy.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Cap myopathy is an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases are not inherited; they result from new mutations in the gene and occur in people with no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Cap myopathy is a rare disorder that has been identified in only a small number of individuals. Its exact prevalence is unknown.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal muscle fiber morphology · Frequent (79-30%)

Any abnormality of the skeletal muscle cell. Muscle fibers are subdivided into two types. Type I fibers are fatigue-resistant and rich in oxidative enzymes (they stain light with the myosin ATPase reaction), and type II fibers are fast-contracting, fatigue-prone, and rich in glycolytic enzymes (these fibers stain darkly). Normal muscle tissue has a random distribution of type I and type II fibers.

High palate · Frequent (79-30%)

Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).

Long face · Frequent (79-30%)

Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).

Motor delay · Frequent (79-30%)

A type of Developmental delay characterized by a delay in acquiring motor skills.

Reduced tendon reflexes · Frequent (79-30%)

A reduction (hyporeflexia) or complete absence (areflexia) of the involuntary muscle contraction normally elicited by a reflex stimulus, such as tapping a deep tendon.

Aortic root aneurysm · Occasional (29-5%)

An abnormal localized widening (dilatation) of the aortic root.

Difficulty climbing stairs · Occasional (29-5%)

Reduced ability to climb stairs.

Difficulty running · Occasional (29-5%)

Reduced ability to run.

Other findings in the same source

From: Orphanet

Additional reported features include Easy fatigability (Occasional (29-5%)); Facial palsy (Occasional (29-5%)); Fatiguable weakness of proximal limb muscles (Occasional (29-5%)); Generalized amyotrophy (Occasional (29-5%)); Generalized hypotonia (Occasional (29-5%)); Gowers sign (Occasional (29-5%)); Hypernasal speech (Occasional (29-5%)); Increased variability in muscle fiber diameter (Occasional (29-5%)); Lower limb amyotrophy (Occasional (29-5%)); Lower limb muscle weakness (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Cap myopathy is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Cap myopathy. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.