RNAse T2-deficient leukoencephalopathy

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

RNAse T2-deficient leukoencephalopathy is a disorder that affects the brain. People with RNAse T2-deficient leukoencephalopathy have neurological problems that become apparent during infancy; the problems generally do not worsen over time (progress). Most affected individuals have severe intellectual disability; muscle stiffness (spasticity); and a delay in developing motor skills such as sitting, crawling, and walking. Some do not learn to walk, and most do not develop the ability to speak. Other neurological features that can occur in RNAse T2-deficient leukoencephalopathy include hearing loss caused by abnormalities in the inner ear (sensorineural deafness), seizures, involuntary writhing movements of the hands (athetosis), uncontrolled muscle tensing (dystonia), and involuntary eye movements (nystagmus). In addition to the neurological problems associated with this disorder, some affected individuals have unusual facial features sometimes described as a "doll-like face."

The neurological problems in this disorder are caused by abnormalities in the brain. People with this condition have leukoencephalopathy, an abnormality of the brain's white matter that can be detected with medical imaging. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In people with RNAse T2-deficient leukoencephalopathy, myelin is not made in sufficient amounts during development, leading to patchy white matter abnormalities (lesions) in the brain. In addition, individuals with RNAse T2-deficient leukoencephalopathy may have cysts in regions of the brain called the temporal lobes and enlargement of the fluid-filled cavities (ventricles) near the center of the brain. The white matter lesions are primarily concentrated around the cysts and the ventricles. An abnormally small head and brain size (microcephaly) often occurs in this disorder.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

RNAse T2-deficient leukoencephalopathy is caused by variants (also called mutations) in the RNASET2 gene. This gene provides instructions for making a protein called ribonuclease T2 (RNAse T2), which is normally abundant in the brain. Ribonucleases help break down RNA, a chemical cousin of DNA. Studies suggest that ribonuclease T2 may also be involved in other functions within cells, such as controlling the development of blood vessels (angiogenesis) and helping to suppress the growth of cancerous tumors. These potential roles of the protein are not well understood.

The RNASET2 gene variants that cause RNAse T2-deficient leukoencephalopathy result in loss of ribonuclease T2 protein function. It is unknown how loss of this protein results in brain abnormalities and neurological problems. Researchers have noted that the signs and symptoms of RNAse T2-deficient leukoencephalopathy are similar to those resulting from infection with a particular virus, called cytomegalovirus (CMV), when it is transmitted to a fetus during pregnancy (congenital CMV). They are seeking to understand how the viral infection, or the body's response to it, and the loss of ribonuclease T2 function could have similar effects on the developing brain. It is thought that both may be related to changes in angiogenesis or an immune system response to RNA that has not been properly broken down.

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 have variants. 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 prevalence of RNAse T2-deficient leukoencephalopathy is unknown. About 50 people with the signs and symptoms of this disorder have been described in the medical literature. However, only about a quarter of these individuals have been confirmed to have the same genetic change that causes RNAse T2-deficient leukoencephalopathy. Researchers suggest that additional genetic changes or other causes may also result in the same pattern of signs and symptoms (phenotype).

Which doctor should you see?

The suggested department for discussing RNAse T2-deficient leukoencephalopathy 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 RNAse T2-deficient leukoencephalopathy. 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.