Fukuyama congenital muscular dystrophy

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Fukuyama congenital muscular dystrophy is an inherited condition that predominantly affects the muscles, brain, and eyes. Congenital muscular dystrophies are a group of genetic conditions that cause muscle weakness and muscle wasting (atrophy) beginning early in life. The signs and symptoms of Fukuyama congenital muscular dystrophy can vary from mild to severe.

Fukuyama congenital muscular dystrophy affects the skeletal muscles, which are the muscles the body uses for movement. The signs and symptoms of the disorder typically begin in early infancy and include a weak cry, difficulty feeding, and weak muscle tone (hypotonia). Weakness of the facial muscles often leads to a distinctive facial appearance including droopy eyelids (ptosis) and an open mouth. In childhood, muscle weakness and joint deformities (contractures) restrict movement and interfere with the development of motor skills such as sitting, standing, and walking. Children with mild Fukuyama congenital muscular dystrophy may be able to stand or walk on their own, while those with severe signs and symptoms may not be able to sit without support.

Fukuyama congenital muscular dystrophy also impairs brain development. People with this condition often have a brain abnormality called cobblestone lissencephaly, in which the surface of the brain has a bumpy, irregular appearance (like that of cobblestones). These irregularities in the structure of the brain lead to delays in the development of motor skills and speech and moderate to severe intellectual disabilities. Social skills are less severely impaired. More than half of all affected children experience seizures.

In some people with Fukuyama congenital muscular dystrophy, vision is impaired. They may also have increased pressure in the eye (glaucoma) or abnormalities in the specialized light-sensitive tissue that lines the back of the eye (retina).

Individuals with Fukuyama congenital muscular dystrophy often develop heart problems in adolescence. These heart problems worsen over time. Severely affected individuals may also develop swallowing difficulties that can lead to a bacterial lung infection called aspiration pneumonia. The serious medical problems associated with Fukuyama congenital muscular dystrophy can shorten the life expectancy of someone with this condition.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Fukuyama congenital muscular dystrophy is caused by variants (also called mutations) in the FKTN gene. This gene provides instructions for making an enzyme called fukutin. Fukutin modifies another protein called alpha-dystroglycan. This modification is necessary for alpha-dystroglycan to function. Alpha-dystroglycan anchors cells to the extracellular matrix, which is the network of molecules that forms in the spaces between cells and provides structural support. In skeletal muscles, alpha-dystroglycan helps stabilize and protect muscle fibers. In the brain, alpha-dystroglycan helps direct the movement (migration) of nerve cells (neurons) during early development.

The most common variant in the FKTN gene reduces the amount of fukutin produced within cells. This impairs the cell's ability to produce functional alpha-dystroglycan. Without enough functional alpha-dystroglycan to stabilize muscle cells, muscle fibers become damaged as they repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to progressive weakness and atrophy of the skeletal muscles.

The lack of functional alpha-dystroglycan also impairs the migration of neurons during the early development of the brain. This leads to the cobblestone lissencephaly seen in children with Fukuyama congenital muscular dystrophy.

Because Fukuyama congenital muscular dystrophy involves problems with alpha-dystroglycan, the condition belongs to a group of disorders called dystroglycanopathies.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Fukuyama congenital muscular dystrophy is more common among people of Japanese ancestry. It is estimated to affect 1 in 25,000 to 50,000 infants born in Japan.

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.

Delayed speech and language development · Very frequent (99-80%)

A degree of language development that is significantly below the norm for a child of a specified age.

EMG abnormality · Very frequent (99-80%)

Abnormal results of investigations using electromyography (EMG).

Flexion contracture · Very frequent (99-80%)

A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.

Gait disturbance · Very frequent (99-80%)

The term gait disturbance can refer to any disruption of the ability to walk.

Global developmental delay · Very frequent (99-80%)

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

Hypoglycosylation of alpha-dystroglycan · Very frequent (99-80%)

A reduction in the degree of glycosylation of alpha-dystroglycan in muscle tissue.

Hypotonia · Very frequent (99-80%)

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

Intellectual disability, severe · Very frequent (99-80%)

Severe intellectual disability (ID) is defined as a type of ID characterized by severely sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 20-34.

Other findings in the same source

From: Orphanet

Additional reported features include Mask-like facies (Very frequent (99-80%)); Muscular dystrophy (Very frequent (99-80%)); Myopathy (Very frequent (99-80%)); Plagiocephaly (Very frequent (99-80%)); Type II lissencephaly (Very frequent (99-80%)); Brachycephaly (Frequent (79-30%)); Camptodactyly of finger (Frequent (79-30%)); EEG abnormality (Frequent (79-30%)); Hydrocephalus (Frequent (79-30%)); Myopia (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Fukuyama congenital muscular dystrophy is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

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

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.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Fukuyama congenital muscular dystrophy. 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.