Leukoencephalopathy with calcifications and cysts

What it is

From: Orphanet

A rare genetic cerebral small vessel disease characterized by leukoencephalopathy and cerebral calcification and cysts due to diffuse cerebral microangiopathy resulting in microcystic and macrocystic parenchymal degeneration. The condition can present at any age from early childhood to late adulthood and manifests as a progressive cerebral degeneration. Symptoms are variable, but restricted to the central nervous systems, and include, among others, slowing of cognitive performance, seizures, and movement disorder with a combination of pyramidal, extrapyramidal, and cerebellar features.

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.

Cerebral calcification · Very frequent (99-80%)

The presence of calcium deposition within the cerebrum.

Intracranial cystic lesion · Very frequent (99-80%)

A cystic lesion originating within the brain.

Leukoencephalopathy · Very frequent (99-80%)

This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells.

Abnormal pyramidal sign · Frequent (79-30%)

Functional neurological abnormalities related to dysfunction of the pyramidal tract.

Ataxia · Frequent (79-30%)

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).

Basal ganglia calcification · Frequent (79-30%)

The presence of calcium deposition affecting one or more structures of the basal ganglia.

Cognitive impairment · Frequent (79-30%)

Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.

Dense calcifications in the cerebellar dentate nucleus · Frequent (79-30%)

Pathological deposition of calcium salts in the dentate nucleus of the cerebellum.

Emotional lability · Frequent (79-30%)

Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.

Intracerebral periventricular calcifications · Frequent (79-30%)

The presence of calcium deposition in the cerebral white matter surrounding the cerebral ventricles.

Mental deterioration · Frequent (79-30%)

Loss of previously present mental abilities, generally in adults.

Rosenthal fibers · Frequent (79-30%)

Thick, elongated, worm-like or corkscrew eosinophilic bundle that are found on H&E staining of the brain in the presence of long standing gliosis, occasional tumors, and some metabolic disorders.

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.

Subcortical white matter calcifications · Frequent (79-30%)

Other findings in the same source

From: Orphanet

Additional reported features include Cerebral hemorrhage (Occasional (29-5%)); Dysarthria (Occasional (29-5%)); Dystonia (Occasional (29-5%)); Focal motor seizure (Occasional (29-5%)); Gait disturbance (Occasional (29-5%)); Global developmental delay (Occasional (29-5%)); Increased intracranial pressure (Occasional (29-5%)); Posterior fossa cyst (Occasional (29-5%)); Spasticity (Occasional (29-5%)); Stroke (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Adolescent; Adult; Childhood; Infancy

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Reported case(s): 50.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Leukoencephalopathy with calcifications and cysts 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 Leukoencephalopathy with calcifications and cysts. 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.