Dysequilibrium syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Dysequilibrium syndrome (DES) is a group of disorders that are characterized by abnormal brain development, which causes intellectual disabilities and problems with balance and coordination (ataxia). The specific signs and symptoms and the severity of the condition can vary among affected individuals.

In people with DES, the part of the brain that coordinates movement (cerebellum) may be unusually small and underdeveloped (cerebellar hypoplasia). This can lead to ataxia that is present from birth and typically does not worsen over time. Additional brain abnormalities may include further loss of tissue (atrophy) in the cerebellum; fewer folds and grooves (gyri) on the surface of the brain; and a small brainstem, which is the area of the brain that connects the brain to the spinal cord.

Children with DES may have low muscle tone (hypotonia) and delayed development of motor skills such as walking. Some affected individuals learn to walk later in childhood, while others are never able to walk independently.

Additional features of DES may include intellectual disabilities that can vary from mild to profound; rapid, involuntary eye movements (nystagmus); and eyes that do not look in the same direction (strabismus). People with DES may also have difficulty speaking (dysarthria) or be unable to speak. Flat feet (pes planus), seizures, and short stature have been reported in some people with DES.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Certain variants (also called mutations) in one of several genes cause DES. There are at least four types of DES, each with a different genetic cause. Variants in the VLDLR gene cause a form of DES called type 1, also sometimes called VLDLR-related cerebellar hypoplasia. This is the most common form of DES.

The VLDLR gene provides instructions for making a protein called a very low-density lipoprotein (VLDL) receptor. This protein plays a critical role in guiding developing nerve cells to the appropriate locations in the brain. Many of the variants in the VLDLR gene that are associated with DES type 1 prevent cells from producing any functional VLDL receptor protein. Without this protein, developing nerve cells cannot reach the parts of the brain where they are needed. This impairs brain development, which leads to the intellectual disabilities and ataxia seen in people with this condition.

Variants in different genes cause the other types of DES and are each responsible for a small percentage of cases.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

DES 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

The exact prevalence of DES is unknown, but more than 75 cases have been reported in the medical literature.

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.

Ataxia · Very frequent (99-80%)

Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).

Gait disturbance · Very frequent (99-80%)

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

Hyperreflexia · Very frequent (99-80%)

Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.

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 · Very frequent (99-80%)

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Abnormality of movement · Frequent (79-30%)

An abnormality of movement with a neurological basis characterized by changes in coordination and speed of voluntary movements.

Cerebral palsy · Frequent (79-30%)

Cerebral palsy describes a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication, and behavior, by epilepsy, and by secondary musculoskeletal problems.

Seizure · Frequent (79-30%)

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

Other findings in the same source

From: Orphanet

Additional reported features include Short stature (Frequent (79-30%)); Skeletal muscle atrophy (Frequent (79-30%)); Strabismus (Frequent (79-30%)); Abnormality of the eye (Occasional (29-5%)); Abnormality of vision (Occasional (29-5%)); Cataract (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 Dysequilibrium syndrome 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 Dysequilibrium syndrome. 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.