RNAse T2-deficient leukoencephalopathy
RNAse T2-deficient leukoencephalopathy is a rare genetic disorder characterized by neurological problems that emerge in infancy and abnormalities in the brain's white matter.
Overview
People with RNAse T2-deficient leukoencephalopathy experience neurological issues that typically become apparent during infancy and generally do not worsen over time. Most affected individuals have severe intellectual disability, muscle stiffness (spasticity), and delays in developing motor skills such as sitting, crawling, and walking. Many do not learn to walk, and most do not develop the ability to speak.
Other neurological features may include:
- Sensorineural deafness (hearing loss caused by inner ear abnormalities)
- Seizures
- Athetosis (involuntary writhing movements of the hands)
- Dystonia (uncontrolled muscle tensing)
- Nystagmus (involuntary eye movements)
Some affected individuals also exhibit unusual facial features, sometimes described as a "doll-like face."
Causes & Brain Abnormalities
The neurological problems are caused by leukoencephalopathy, an abnormality of the brain's white matter. White matter consists of nerve fibers covered by myelin, a fatty substance that insulates fibers and promotes rapid nerve impulse transmission. In this disorder, myelin is not produced in sufficient amounts, leading to patchy white matter abnormalities (lesions). Additionally, individuals may have cysts in the brain and enlarged fluid-filled cavities (ventricles). An abnormally small head and brain size (microcephaly) often occurs.
The condition is caused by variants in the RNASET2 gene, which provides instructions for making the protein ribonuclease T2. This protein is abundant in the brain and helps break down RNA. While its exact role is not fully understood, it is believed to be involved in blood vessel development (angiogenesis) and tumor suppression.
Inheritance
This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have variants. Parents of an affected individual typically carry one copy of the altered gene but do not show signs or symptoms of the condition.
Frequency
The prevalence is unknown, with about 50 people described in medical literature. Only about a quarter of these cases have been confirmed to have the specific genetic change associated with the disorder, suggesting other genetic or external factors may cause a similar pattern of symptoms.