Last updated:
11/5/2025
Years published: 2025
NORD gratefully acknowledges Nicole Litt and Joe Katakowski, PhD, RTW Foundation, Lenny’s Cure for CONDSIAS and Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for the preparation of this report.
Stress-Induced Childhood-Onset Neurodegeneration with Variable Ataxia and Seizures (CONDSIAS) is a very rare inherited disorder. Symptoms usually begin in childhood and include movement problems (ataxia), seizures, developmental regression (loss of previously learned skills) and hearing loss. The disorder is caused by changes (variants) in the ADPRS (ADPRHL2) gene. It is passed down in an autosomal recessive pattern, meaning an affected child inherits two ADPRS gene variants, one from each parent. There is no cure at this time. Current treatment focuses on managing symptoms.¹
People with CONDSIAS may have:1,2,3
Symptom onset and severity vary widely. Symptoms of early-onset forms typically begin before age two with developmental delays and epilepsy. Symptoms of later-onset forms begin during or after childhood with movement issues or behavioral disturbances, sometimes without seizures and generally with better prognosis. Symptoms often get worse over time. Stressful events such as fever or illness may trigger a worsening of symptoms.¹
CONDSIAS is caused by changes (variants) in the ADPRS (ADPRHL2) gene, which provides instructions for making an enzyme called ARH3. This enzyme plays a key role in protecting cells under stress by removing harmful chemical tags known as ADP-ribose from proteins and DNA. When ARH3 is missing or not working correctly, these tags build up and interfere with normal cell function, especially in nerve cells of the brain. This buildup can disrupt the way genes are regulated and how cells repair DNA damage, leading to cellular dysfunction. Because brain cells are particularly sensitive to this type of damage, especially during early development, symptoms often begin in childhood. As time goes on, the continued buildup of damage may also affect mature brain cells, which helps explain the progressive nature of the disease.1
Current theories about loss-of-function gene variants show that when cells are under stress, they have higher levels of ADP-ribose than normal cells. This suggests that the DNA damage repair process controlled by ARH3 doesn’t work properly in CONDSIAS.1
Inheritance
CONDSIAS follows an autosomal recessive inheritance pattern. Recessive genetic disorders occur when an individual inherits a disease-causing gene variant from each parent. If an individual receives one normal gene and one disease-causing gene variant, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the gene variant and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
CONDSIAS is extremely rare, with only a small number of cases reported worldwide.1-5
The exact prevalence is unknown.
A diagnosis of CONDSIAS may be suspected based on clinical history such as childhood onset of ataxia, seizures, regression of speech or movement.¹
Genetic testing that shows two disease-causing variants in the ADPRS (ADPRHL2) gene confirms the diagnosis.¹
There is currently no cure for CONDSIAS.¹ Management is supportive and depends on the specific problems that the affected person has. It may include:
• Anti-seizure medicines to control seizures
• Physical therapy to improve movement and strength
• Speech therapy to help with communication
• Hearing aids or cochlear implants for hearing loss
In one reported case, the authors highlighted some treatment options that have being used in individual cases. Among these, the antibiotic doxycycline emerged as a promising treatment and showed improvement in the patient’s symptoms.4 This is still experimental and not an approved treatment.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
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https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
http://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
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