Congenital Intrauterine Infection-Like Syndrome

Other names
Types
Causes
Symptoms and signs
Diagnostic tests
Non-pharmacological treatments (therapies and others)
Drug treatments
Dietary molecular supplements
Immunity-booster / regenerative / stem-cell–oriented drugs
Surgeries and procedures
Preventions
When to see doctors
What to eat and what to avoid
Frequently asked questions

Congenital intrauterine infection-like syndrome is a term doctors used when a baby looks as if they were infected in the womb (like TORCH infections such as cytomegalovirus or rubella), but all infection tests are negative. Babies often have small head size (microcephaly), brain calcifications seen on scans, feeding problems, seizures, and developmental delay. Over the last two decades, many of these babies have been found to have Aicardi-Goutières syndrome (AGS) or “pseudo-TORCH” conditions—genetic disorders that cause the immune system to act as if a virus is present all the time. This chronic “interferon alarm” inflames the brain and other organs, creating the same signs that infections produce, even though no infection is there. Distinguishing CIILS/AGS from true infections is essential for counseling families and planning care. PubMed+4Orpha+4NCBI+4

In many CIILS cases, genes that normally dispose of leftover bits of DNA/RNA or regulate antiviral alarms are faulty. Cells then mistake normal cell debris for a virus and turn on type-I interferon signaling all the time. This “false fire alarm” injures white matter, causes brain atrophy, and leaves tiny calcium deposits in the brain. This same pathway explains why these babies look like they have a congenital infection even when they do not. PubMed+2AJNR+2

Congenital intrauterine infection-like syndrome is a rare genetic condition in which a newborn baby looks as if they were infected by a TORCH infection (like cytomegalovirus) before birth, but there is no actual infection. Babies usually have a small head (microcephaly), hard calcium deposits inside the brain (intracranial calcifications), and early brain-related problems such as seizures or stiff muscles. Doctors used to think these signs always meant an infection, but in this syndrome the problem comes from differences in the baby’s genes that disturb early brain development or the body’s antiviral “interferon” system. Orpha+1 Because it mimics infection, families may receive the wrong counseling if the genetics are missed. Correct diagnosis helps with care plans, seizure control, therapy services, recurrence risk in future pregnancies, and—sometimes—targeted treatments that calm the overactive interferon pathway. Lippincott Journals+2RUPress+2

Other names

Doctors and researchers may use several names that mean the same or closely related things:

Pseudo-TORCH syndrome (PTS) – “TORCH-like” signs without proven infection. National Organization for Rare Disorders
Congenital intrauterine infection-like syndrome – the Orphanet name for this group. Orpha
Baraitser–Reardon / pseudo-TORCH – an early description of the condition. ScienceDirect
Band-like calcification with simplified gyration and polymicrogyria (BLC-PMG) – a specific pseudo-TORCH pattern caused by changes in the OCLN gene. ScienceDirect+1
Type I interferonopathies (such as Aicardi-Goutières syndrome) – conditions that often mimic congenital infection, with similar brain calcifications and early neurologic problems. MedlinePlus+2NCBI+2

Types

You may see clinicians group cases by the main underlying pathway or by the gene involved:

Tight-junction/brain-development type – examples include OCLN-related BLC-PMG, where the brain’s folding is simplified and calcifications appear in bands. This reflects problems with occludin, a protein that helps seal cells together during early brain formation. ScienceDirect+1
Type I interferonopathy type – examples include USP18 deficiency (pseudo-TORCH type 2) and Aicardi-Goutières–spectrum genes. In these, the body’s antiviral alarm system is stuck “on,” causing inflammation that injures the developing brain and mimics infection. RUPress+2NEJM+2
Unspecified/overlap type – babies who have a clear pseudo-TORCH picture but the exact gene is not yet identified, or who sit between the brain-malformation and interferonopathy groups. Wiley Online Library

Causes

These “causes” are the most supported genetic and biological reasons that can produce a TORCH-like picture without a real infection. Each item explains what changes and how that leads to the baby’s signs.

OCLN gene changes (occludin)
Occludin helps build tight junctions between cells in the developing brain. Harmful variants can produce BLC-PMG with band-like calcifications and simplified brain folds, leading to microcephaly and seizures. ScienceDirect+1
USP18 deficiency (pseudo-TORCH type 2)
USP18 normally turns off the type I interferon signal after it does its job. If USP18 is missing, interferon inflammation keeps burning, damaging the brain before birth and causing severe neonatal illness that looks like infection. RUPress+1
TREX1 variants
TREX1 clears stray DNA. When it fails, the immune system mistakenly thinks a virus is present, driving interferon-mediated brain inflammation and calcifications similar to congenital infections. (Part of the Aicardi-Goutières spectrum.) NCBI
RNASEH2A/B/C variants
These genes help process RNA/DNA hybrids. Faults trigger interferon activation and intracranial calcifications, microcephaly, and developmental delay. NCBI
SAMHD1 variants
Disrupted control of nucleic acids activates antiviral pathways chronically, creating an “infection-like” brain injury pattern. NCBI
ADAR1 variants
ADAR edits RNA; loss of control makes normal RNA look viral, turning on interferon and producing calcifications and early neurologic disease. NCBI
IFIH1 (MDA5) variants
MDA5 senses viral RNA. Overactivity keeps the interferon alarm on, injuring the fetal brain and white matter. NCBI
RNASEH2D / related complex defects
Rare alterations in associated complex members can phenocopy AGS features and the pseudo-TORCH picture. NCBI
CMPK2 variants
A mitochondrial nucleotide kinase linked to interferonopathy; dysfunction contributes to neuroinflammation and calcifications. (Reported within AGS-spectrum literature.) NCBI
SKIV2L variants
Part of RNA surveillance; failure can activate innate antiviral responses in utero, producing infection-like features. NCBI
OCLN regulatory region defects
Even when the coding gene is intact, control-region changes may reduce occludin expression and lead to BLC-PMG features. PubMed
Other tight-junction gene defects
Genes working with occludin (tight-junction complex) may indirectly cause similar malformations and calcifications. PubMed
Unknown interferon-pathway genes
Some infants have a strong interferon “signature” (high interferon-stimulated genes) but no known variant yet; research suggests more genes remain to be discovered. RUPress
Aicardi-Goutières syndrome (broad genetic spectrum)
Clinical AGS is a prime mimic of congenital infection, with microcephaly and basal ganglia calcifications despite negative infection testing. MedlinePlus+1
Interferon-driven placental inflammation
Overactive interferon can also inflame the placenta, limiting blood flow and nutrients, worsening growth and brain injury. (Mechanistic inference from interferonopathy literature.) RUPress
Early in-utero seizures from cortical malformation
Abnormal brain folding (e.g., BLC-PMG) predisposes to seizures even before birth, which can aggravate developmental injury. ScienceDirect
White-matter injury from chronic inflammation
Long-lasting interferon signaling harms myelin and white matter, contributing to spasticity and delayed milestones. MedlinePlus
Calcification from inflammatory micro-injury
Ongoing sterile inflammation deposits calcium in brain tissues, creating the classic CT-visible spots. AAFP
Secondary metabolic stress in the fetus
Inflammation and poor placental function can trigger oxidative and metabolic stress that compounds brain injury. (Mechanistic inference consistent with interferonopathy pathobiology.) RUPress
Currently unidentified Mendelian causes
New genes continue to be reported; some families show a clear autosomal-recessive pattern with pseudo-TORCH features but no known mutation yet. Wiley Online Library

Symptoms and signs

Microcephaly (small head size)
Head growth is reduced because the developing brain is injured early. This is often visible at birth or in late pregnancy. Orpha
Seizures
Abnormal electrical activity in the brain may start in the newborn period and can be hard to control. Seizures can appear as stiffening, jerking, or staring spells. Wiley Online Library
Spasticity or stiff muscles
Damage to motor pathways leads to increased tone, scissoring of the legs, and delayed motor skills. Wiley Online Library
Developmental delay
Children may roll, sit, walk, and talk later than expected because of brain injury that started before birth. Orpha
Feeding difficulties and poor weight gain
Weak suck, reflux, or fatigue are common in infants with neurologic involvement.
Jitteriness or irritability
Neurologic irritability can look like frequent startles, fussiness, or poor sleep.
Abnormal muscle tone (too high or too low)
Some babies are floppy at first and later become stiff as spasticity appears.
Hearing or vision problems
The brain’s processing centers may be affected, and structural eye issues can co-occur.
Abnormal movements
Tremors, chorea, or dystonia may appear with basal ganglia injury.
Small size at birth or growth restriction
Placental inflammation or metabolic stress can reduce growth.
Fevers without infection (in some interferonopathies)
Episodes of unexplained fever can occur even when cultures are negative. MedlinePlus
Skin changes (rare)
Aicardi-Goutières can cause chilblain-like lesions on fingers or toes in older infants. NCBI
Low platelets or enlarged liver/spleen (some cases)
Blood and organ findings may mimic TORCH infections but are not caused by microbes. AAFP
Abnormal head ultrasound during pregnancy
Band-like calcifications or simplified brain folding can be seen on fetal imaging in some forms. ScienceDirect
Learning difficulties and cerebral palsy features later on
Long-term outcomes vary; many children need ongoing therapies and supportive care. Orpha

Diagnostic tests

Physical examination (bedside checks)

Head-circumference measurement
The baby’s head size is measured and plotted on a growth chart. A value much below average supports microcephaly and prompts imaging. Orpha
Neurologic exam
Doctors look at tone, reflexes, posture, and movements. Stiffness, poor suck, or abnormal reflexes suggest brain involvement.
Developmental screening
Simple bedside checks of eye contact, tracking, social smile, and early motor skills help set a baseline and guide early intervention.
Skin, liver, and spleen exam
Pale skin, bruising, or an enlarged liver/spleen can appear in pseudo-TORCH and in true infections; the exam helps decide which lab tests to send. AAFP

Manual/functional tests (hands-on assessments)

Feeding and swallow evaluation
A speech or occupational therapist checks latch, suck–swallow–breathe coordination, and aspiration risk to plan safe feeding.
Standardized tone and posture scales
Physiotherapists use gentle maneuvers to rate spasticity or hypotonia, guiding therapy goals.
Hearing screening (OAE/ABR bedside protocols)
Early checks flag hearing loss so supports can start promptly.

Laboratory and pathological tests

Infection workup (TORCH serology/PCR) – usually negative
Blood and sometimes cerebrospinal fluid (CSF) are tested for TORCH pathogens. In pseudo-TORCH, these do not show infection, which is a key clue. National Organization for Rare Disorders
Interferon signature
A blood test that measures interferon-stimulated genes. A strong “signature” suggests an interferonopathy such as USP18 deficiency or AGS. RUPress
CSF studies (cell count, protein, neopterin)
In interferonopathies, CSF can show elevated neopterin and mild inflammation, mimicking viral infection but without a pathogen. NCBI
Basic labs (CBC, liver enzymes, platelets)
Low platelets or elevated liver tests can accompany the syndrome and help monitor overall health. AAFP
Genetic testing: gene panel, exome, or genome
Testing can identify changes in OCLN, USP18, TREX1, RNASEH2 genes, and others. Finding the exact variant confirms diagnosis and guides counseling. ScienceDirect+2RUPress+2
Targeted parental testing
If a variant is found in the child, parents can be checked to clarify inheritance (often autosomal recessive) and recurrence risk. Wiley Online Library

Electrodiagnostic tests

Electroencephalogram (EEG)
EEG records brain waves to detect seizures and guide anti-seizure treatment plans; abnormal background may reflect widespread injury. Wiley Online Library
Evoked potentials (as needed)
Tests of visual or auditory pathways can help assess brain function when the exam is hard to interpret in a newborn.

Imaging tests

Cranial ultrasound (bedside)
A quick, radiation-free scan through the soft spot can detect big calcifications, bleeding, or malformations and is useful in the NICU.
Head CT
CT is excellent at showing intracranial calcifications—the hallmark white specks or bands seen in pseudo-TORCH conditions. AAFP
Brain MRI
MRI shows brain structure in detail: simplified brain folds, white-matter injury, basal ganglia involvement, and brain atrophy help narrow the cause. ScienceDirect
Fetal ultrasound/MRI (during pregnancy)
In high-risk pregnancies, prenatal imaging can detect microcephaly, calcifications, or simplified gyration patterns and trigger early genetic work-up. ScienceDirect
Ophthalmology imaging (as indicated)
Retinal exam and imaging check for optic-nerve or retinal changes that sometimes accompany brain maldevelopment.

Non-pharmacological treatments (therapies and others)

Each item includes what it is, purpose, and mechanism in simple language (about 150 words).

Early developmental intervention
Daily, structured play-based therapy to encourage movement, language, eye contact, and problem-solving from the first months of life. Purpose: give the brain many chances to learn skills even if development is delayed. Mechanism: repeated stimulation strengthens surviving neural circuits and supports neuroplasticity; families learn home activities to repeat all day. Starting early improves long-term function in many infant encephalopathies and is standard care once infections are excluded and AGS/CIILS is suspected. NCBI+1
Physiotherapy (gross-motor therapy)
Hands-on exercises that train head control, rolling, sitting, standing, and safe transfers; uses positioning, splints, and standing frames if needed. Purpose: prevent contractures, improve posture, reduce pain, and support mobility. Mechanism: stretching, strengthening, and motor learning reduce spasticity-related stiffness and help joints move normally, protecting bones and lungs by promoting activity. SpringerLink
Occupational therapy (fine-motor and daily skills)
Practical training for feeding, hand use, dressing, and play; adapts cups, spoons, and seating. Purpose: promote independence and caregiver ease. Mechanism: task-specific practice builds motor plans and sensory processing; adaptive tools reduce energy cost and frustration. SpringerLink
Speech-language therapy (including feeding therapy)
Work on safe swallowing, early communication, and later speech or augmentative communication. Purpose: reduce aspiration risk, improve nutrition and interaction. Mechanism: oromotor exercises and paced feeding improve swallow coordination; communication systems (pictures/devices) give the child a “voice” while speech develops. SpringerLink
Nutritional optimization and growth monitoring
Dietitians tailor calories, protein, and micronutrients; consider thickened feeds or tube feeding if unsafe swallow. Purpose: maintain growth and brain energy supply. Mechanism: adequate calories/protein support myelination and immune function; safe textures lower aspiration. NCBI
Seizure-safety education and first-aid training
Teach caregivers seizure recognition, positioning, and rescue plans. Purpose: reduce injury and speed treatment. Mechanism: clear home protocols shorten time to care and prevent complications. NCBI
Vision and hearing services
Early screening and aids (glasses, hearing devices) if deficits are found. Purpose: boost learning by fixing input channels. Mechanism: better sensory input improves attention and development; many encephalopathies affect visual/hearing pathways. SpringerLink
Spasticity management with positioning and orthoses
Night splints, ankle-foot orthoses, seating systems, and regular stretching. Purpose: prevent contractures and improve comfort. Mechanism: sustained neutral alignment reduces muscle shortening and joint deformity. SpringerLink
Respiratory hygiene program
Chest physiotherapy, suction training, and vaccination to prevent infections. Purpose: reduce hospitalizations. Mechanism: airway clearance and immunization lower pneumonia risk in neuromotor disorders. SpringerLink
Pain and irritability behavioral plan
Identify triggers (reflux, constipation, tone spikes) and non-drug calming routines. Purpose: comfort and sleep. Mechanism: consistent routines, gentle stretching, warm baths, and massage reduce stress and tone. SpringerLink
Family psychosocial support
Counseling, peer groups, and respite care. Purpose: lower caregiver burnout and improve adherence. Mechanism: social support reduces stress hormones and improves family functioning. SpringerLink
Genetic counseling
Explain inheritance, recurrence risks, and options for future pregnancies. Purpose: informed family planning. Mechanism: identifying the exact gene guides carrier testing and prenatal/early testing. NCBI+1
Educational therapy and inclusive schooling
Individualized education plans (IEPs) with accommodations. Purpose: maximize learning. Mechanism: tailored goals and assistive tech match abilities and prevent frustration. SpringerLink
Safe feeding positioning and reflux precautions
Upright feeds, paced volumes, and reflux strategies. Purpose: reduce vomiting, pain, and aspiration. Mechanism: gravity and pacing improve swallow-breath timing. NCBI
Sleep hygiene program
Consistent bedtime routine, light control, and calming inputs. Purpose: better sleep for brain recovery. Mechanism: stable circadian cues improve mood, tone, and seizure threshold. SpringerLink
Orthopedic surveillance pathway
Hip-spine X-ray monitoring in children with spasticity. Purpose: catch hip migration and scoliosis early. Mechanism: regular checks allow early bracing or botulinum/orthopedic referral. SpringerLink
Augmentative and alternative communication (AAC)
Picture boards or speech-generating devices. Purpose: reduce frustration and improve participation. Mechanism: bypasses oral-motor limits and builds language pathways. SpringerLink
Bone health support (non-drug)
Weight-bearing with a standing frame, sunlight, and dietary calcium. Purpose: reduce fractures in non-ambulant children. Mechanism: mechanical loading strengthens bones. SpringerLink
Transition planning to long-term care
Structured handover from pediatric to adult services in adolescence. Purpose: continuity of care. Mechanism: early planning prevents gaps in seizure, spasticity, nutrition, and social support. SpringerLink
Regular reassessment and surveillance imaging when indicated
Use MRI/CT judiciously to monitor white matter and calcifications if it changes management. Purpose: guide therapy; avoid unnecessary radiation. Mechanism: imaging correlates with clinical changes and helps rule out new problems. AJNR

Drug treatments

For safety, pediatric dosing must be individualized by specialists; many uses are off-label and evolving. I’m giving classes, typical timing, purpose, general mechanisms, and key cautions. Please treat these as education, not medical orders.

Antiseizure medicines (e.g., levetiracetam, valproate, topiramate)
Class: antiepileptic drugs. Timing: started when seizures are confirmed. Purpose: reduce seizures and protect developing brain. Mechanism: stabilize neuronal firing (e.g., GABAergic modulation, sodium/calcium channel effects). Side effects: sleepiness, behavior change, liver/platelet issues (valproate), appetite change; drug–drug interactions must be monitored. Evidence supports standard seizure control in AGS/CIILS similar to other infant encephalopathies. NCBI
Spasticity medications (oral baclofen, tizanidine; focal botulinum toxin)
Class: antispasticity; neuromuscular blockade. Timing: persistent tone interfering with care. Purpose: reduce stiffness and pain. Mechanism: baclofen enhances spinal GABA_B inhibition; botulinum blocks acetylcholine at neuromuscular junction for targeted muscles. Side effects: sedation, weakness, constipation (baclofen); localized weakness (botulinum). SpringerLink
Gastro-esophageal reflux and constipation regimens
Class: acid suppression, prokinetics, osmotic laxatives. Timing: as symptoms arise. Purpose: comfort, growth, lower aspiration risk. Mechanism: reduce acid injury and improve motility; stool softening prevents pain. Side effects: electrolyte shifts, diarrhea, or constipation depending on agent. NCBI
Vitamin D ± calcium (medical supplementation)
Class: micronutrient therapy. Timing: deficiency risk or low bone density. Purpose: bone health. Mechanism: supports mineralization; often combined with weight-bearing. Side effects: rare hypercalcemia if overdosed; monitor levels. SpringerLink
JAK inhibitors (e.g., ruxolitinib, baricitinib, tofacitinib – evolving use)
Class: Janus kinase pathway inhibitors. Timing: selected AGS phenotypes under expert protocols. Purpose: dampen the overactive type-I interferon pathway. Mechanism: blocks cytokine signaling downstream of interferon receptors. Side effects: infection risk, cytopenias, liver enzyme rise; careful monitoring required. Reports suggest improvement in systemic/inflammatory features, but effects on neurodevelopment are uncertain and research continues. PubMed+2SpringerLink+2
Reverse transcriptase inhibitor (RTI) combinations (e.g., abacavir + lamivudine + zidovudine in studies)
Class: antiretroviral RTIs. Timing: clinical trials and compassionate protocols. Purpose: reduce interferon signaling triggered by nucleic acid by-products. Mechanism: inhibit endogenous reverse transcription implicated in AGS biology. Side effects: anemia, neutropenia, mitochondrial toxicity; close lab monitoring needed. Early trials show reduced interferon signatures; a prospective study is ongoing. PubMed Central+1
Interferon-signature–guided anti-inflammatories (short steroid courses in specific flares)
Class: corticosteroids. Timing: acute inflammatory crises. Purpose: symptom control. Mechanism: broad cytokine suppression. Side effects: immunosuppression, growth impact, mood changes; tapered plans recommended. SpringerLink
Analgesics and antipyretics (acetaminophen; cautious NSAID use)
Class: pain/fever control. Timing: as needed for comfort. Purpose: reduce pain, irritability, and fever. Mechanism: central COX inhibition (acetaminophen); peripheral COX inhibition (NSAIDs). Side effects: liver risk with overdose; NSAIDs can affect kidneys/gut—pediatric dosing precision is essential. SpringerLink
Antispasmodic intrathecal baclofen (specialty use)
Class: GABA_B agonist via pump. Timing: severe generalized spasticity not controlled by oral meds. Purpose: reduce whole-body tone and pain. Mechanism: direct spinal delivery lowers systemic side effects. Side effects: pump complications, withdrawal if interrupted. SpringerLink
Antiemetics and feed-comfort meds (e.g., ondansetron when appropriate)
Class: 5-HT3 antagonists. Timing: troublesome vomiting with feeds. Purpose: improve feeding tolerance. Mechanism: blocks serotonin-mediated nausea pathways. Side effects: constipation, QT prolongation risk; dosing adjusted by weight. SpringerLink
Bone health medications (when indicated)
Class: bisphosphonates in selected cases. Timing: recurrent fractures or very low bone density under specialist care. Purpose: strengthen bone. Mechanism: reduce bone resorption. Side effects: flu-like symptoms, hypocalcemia risk. SpringerLink
Sialorrhea (drooling) control
Class: anticholinergics or botulinum to salivary glands. Timing: aspiration risk or skin breakdown. Purpose: safer, drier mouth care. Mechanism: lowers saliva production. Side effects: dry mouth, constipation, thickened secretions. SpringerLink
Sleep supports (melatonin under guidance)
Class: chronobiotic. Timing: chronic sleep initiation problems. Purpose: better sleep architecture. Mechanism: circadian phase support. Side effects: morning drowsiness; check interactions. SpringerLink
Antireflux acid suppression (short-term, targeted)
Class: H2 blockers/PPIs. Timing: confirmed reflux-related pain/aspiration. Purpose: comfort, feeding safety. Mechanism: reduces acid production. Side effects: infection risk if long term; reassess need regularly. NCBI
Anticontracture chemodenervation cycles
Class: onabotulinumtoxinA. Timing: focal spasticity; combined with therapy and splints. Purpose: ease care and positioning. Mechanism: temporary muscle relaxation. Side effects: local weakness; dosing weight-based. SpringerLink
Constipation regimen (PEG 3350, fiber, fluids)
Class: osmotic laxatives/nutrition. Timing: common in low-mobility children. Purpose: comfort, reduce reflux and irritability. Mechanism: draws water into stool. Side effects: bloating; titrate to effect. SpringerLink
Antispasticity benzodiazepines (select, short-term)
Class: GABA_A modulators. Timing: nighttime spasms or procedures. Purpose: short relief of spasms/anxiety. Mechanism: enhances inhibitory tone. Side effects: sedation, tolerance, dependence risk; specialist oversight. SpringerLink
Antisense/RNA-targeted experimental agents (research setting)
Class: antisense oligonucleotides targeting interferon pathways (preclinical/early translational). Timing: trials only. Purpose: reduce interferon-driven neuroinflammation. Mechanism: gene-level modulation of IFN-α signaling. Side effects: unknown/being defined; not standard care. AGS Advocacy Association
Broad supportive antimicrobials (only when true infections occur)
Class: antibiotics/antivirals. Timing: proven infection. Purpose: treat real infections promptly because some children are fragile. Mechanism: pathogen-specific. Side effects: drug-specific; avoid unnecessary courses in noninfectious flares. accessanesthesiology.mhmedical.com
Anti-inflammatory adjuncts under research protocols
Class: pathway-directed agents (e.g., IFNAR blockers under investigation). Timing: trials/specialist centers. Purpose: precisely calm interferon signaling. Mechanism: block receptor or downstream signal. Side effects: immunosuppression; expert monitoring. SpringerLink

Dietary molecular supplements

Always use clinician guidance; interactions and pediatric safety vary.

Omega-3 fatty acids (DHA/EPA)
Dose (general nutrition ranges, clinician-guided): weight-adjusted pediatric dosing. Function: anti-inflammatory lipid mediators. Mechanism: shift eicosanoid balance and support neuronal membrane fluidity; may gently modulate neuroinflammation alongside standard care. SpringerLink
Vitamin D
Dose: individualized by blood level. Function: bone and immune modulation. Mechanism: nuclear receptor signaling supports bone mineralization and may temper excessive immune signals. SpringerLink
Vitamin B12 and folate (when deficient)
Dose: lab-guided. Function: myelin and DNA synthesis. Mechanism: supports remyelination pathways and hematologic health. SpringerLink
Medium-chain triglyceride (MCT) oil (feeding formula adjunct)
Dose: dietitian-directed percentage of calories. Function: easy calories for growth. Mechanism: rapidly absorbed fats support energy when feeding volumes are small. NCBI
Calcium (with vitamin D, when indicated)
Dose: age-based totals under dietitian guidance. Function: bone strength. Mechanism: substrate for mineralization. SpringerLink
Iron (only if deficient)
Dose: ferritin-guided. Function: prevent anemia, support development. Mechanism: hemoglobin synthesis and myelination co-factors. SpringerLink
Zinc (deficiency states)
Dose: lab-guided. Function: enzyme cofactor and immune support. Mechanism: supports growth and wound healing. SpringerLink
Probiotics (selected strains for reflux/constipation)
Dose: product-specific pediatric guidance. Function: gut comfort and stooling patterns. Mechanism: microbiome modulation may reduce GI symptoms that worsen irritability and feeding. SpringerLink
Sodium bicarbonate/citrate (only for specific metabolic needs)
Dose: specialist-set. Function: address acidosis if present. Mechanism: buffer therapy; not routine. SpringerLink
Multivitamin (when diet is limited)
Dose: age-appropriate daily. Function: cover micronutrient gaps. Mechanism: prevents deficiencies during prolonged feeding challenges. SpringerLink

Immunity-booster / regenerative / stem-cell–oriented drugs

JAK inhibitors (ruxolitinib/baricitinib/tofacitinib)
Dose: specialist protocols only. Function: immunomodulation. Mechanism: blocks interferon-driven signaling to quiet the chronic antiviral “alarm.” Early reports show systemic benefit; neurological outcomes remain under study. PubMed+1
Reverse transcriptase inhibitor combos (ABC+3TC+AZT in studies)
Dose: trial protocols. Function: pathway dampening. Mechanism: targets endogenous reverse transcription thought to fuel interferon activation; reduces interferon “signature” in small studies. PubMed Central+1
Antisense oligonucleotides (IFN pathway-targeted; preclinical/early)
Dose: research only. Function: gene-level tuning. Mechanism: reduces interferon receptor/ligand activity to lower neuroinflammation in models. AGS Advocacy Association
Bone-health agents (bisphosphonates) in fragile bone
Dose: specialist-set infusions. Function: structural support. Mechanism: inhibit bone resorption to lower fracture risk in non-ambulant children. SpringerLink
Intrathecal baclofen (device-delivered GABA_B agonist)
Dose: pump-titrated. Function: tone modulation for comfort and care. Mechanism: enhances spinal inhibition to reduce whole-body spasticity. SpringerLink
Targeted anti-IFN biologics (concept stage/early exploration)
Dose: trial-only. Function: selective pathway block. Mechanism: interferon-receptor blockade to quell the upstream driver of inflammation. SpringerLink

Surgeries and procedures

Gastrostomy tube (G-tube)
Placed through the abdomen into the stomach to give safe nutrition when swallowing is unsafe or feeding is too slow. Why: protect lungs from aspiration, support growth, and ease medication delivery. NCBI
Intrathecal baclofen pump implantation
A small pump places baclofen directly into spinal fluid for severe spasticity. Why: whole-body tone relief when oral meds fail and to improve comfort and care. SpringerLink
Orthopedic procedures (tendon lengthening/hip reconstruction)
Surgery to release tight tendons or stabilize hips if dislocation risk develops. Why: reduce pain, improve sitting/positioning, and prevent long-term deformity. SpringerLink
Salivary-gland botulinum injections or duct procedures
Interventions to control severe drooling. Why: reduce aspiration risk and skin breakdown around the mouth and chin. SpringerLink
Feeding tube conversions or fundoplication (select cases)
Advanced anti-reflux procedures if medical care fails and aspiration persists. Why: protect lungs and stabilize nutrition. NCBI

Preventions

Vaccinations on time to prevent real infections that fragile children tolerate poorly. accessanesthesiology.mhmedical.com
Seizure-safety plan at home and school to avoid injuries. NCBI
Aspiration prevention with feeding therapy and safe textures. NCBI
Contracture prevention with daily stretching and orthoses. SpringerLink
Hip-spine surveillance to catch orthopedic issues early. SpringerLink
Nutrition monitoring with growth charts and labs. NCBI
Constipation programs to lower reflux and irritability. SpringerLink
Sleep hygiene to improve behavior and seizure threshold. SpringerLink
Infection-control habits (hand hygiene, early treatment plans). accessanesthesiology.mhmedical.com
Genetic counseling before future pregnancies to discuss risk and options. NCBI+1

When to see doctors

Seek medical care urgently for new or worsening seizures, repeated choking or pneumonia, feeding refusal with weight loss, high fevers, severe vomiting or dehydration, sudden increase in stiffness or weakness, uncontrolled pain/irritability, or any rapid developmental regression. Regular follow-ups with neurology, rehabilitation, nutrition, and genetics are important even when your child seems “stable.” NCBI+1

What to eat and what to avoid

Aim for high-calorie, nutrient-dense meals in small volumes; consider energy-rich formulas if advised. NCBI
Thicken liquids if swallow is uncoordinated, per therapist guidance. NCBI
Plenty of fiber and fluids to prevent constipation; adjust with your clinician. SpringerLink
Ensure adequate protein for growth and tissue repair. NCBI
Maintain vitamin D and calcium intake for bone health. SpringerLink
Avoid hard-to-chew textures that raise choking risk; tailor texture to skills. NCBI
Limit reflux triggers (large, fast feeds; lying flat right after meals). NCBI
Do not self-start supplements or herbal products without pediatric guidance. SpringerLink
If growth lags, discuss MCT-enriched formulas with your dietitian. NCBI
For tube-fed children, follow sterile handling and pump guidelines to prevent infections. NCBI

Frequently asked questions

Is CIILS an infection?
No. It looks like one, but most cases are noninfectious interferonopathies like AGS; infection tests are negative. Orpha+1
Why does my child’s brain have calcifications?
Chronic interferon-driven inflammation injures brain tissue and leaves calcium deposits—also seen in infections, which is why the conditions can be confused. AJNR
How is CIILS/AGS diagnosed?
Rule out TORCH infections first; then consider genetic testing panels or exome sequencing when signs fit. NCBI+1
Is there a cure?
There is no established cure yet. Care focuses on seizures, tone, feeding, growth, and family support. Targeted therapies like JAK inhibitors or RTIs are being studied. PubMed+1
What is the outlook?
Outcomes vary by gene and severity. Early supportive care improves comfort and function; some children achieve meaningful milestones. NCBI
Can vaccines cause this?
No. AGS/CIILS is genetic and immune-pathway–driven. Vaccines protect fragile children from real infections. accessanesthesiology.mhmedical.com
Will another baby be affected?
Recurrence risk depends on the gene and inheritance (often autosomal recessive). Genetic counseling explains exact risks and options. NCBI+1
Why are antiseizure medicines needed?
Because uncontrolled seizures harm development and safety; medication lowers seizure burden. NCBI
What do JAK inhibitors do?
They block signals from interferon receptors, aiming to turn down the chronic antiviral alarm. Benefits on non-brain symptoms are reported; brain benefits remain under study. PubMed
What are “reverse transcriptase inhibitors” doing here?
They may reduce the stimulus that keeps interferon switched on. Trials are in progress; not standard for every child. PubMed Central+1
Why is feeding help so important?
Good nutrition fuels growth and brain repair and lowers lung risks from aspiration. NCBI
Are brain scans repeated often?
Only when results could change care; doctors try to limit radiation and anesthesia exposures. AJNR
Is CIILS the same as pseudo-TORCH?
They’re overlapping terms. Pseudo-TORCH describes the “infection-like” picture without infection; many such cases are AGS. National Organization for Rare Disorders+1
Which specialists should be involved?
Neurology, genetics, rehabilitation (PT/OT/SLP), nutrition/feeding, and primary care—plus orthopedics if needed. NCBI+1
Where can families read more?
GeneReviews and NORD provide reliable, plain-language summaries of AGS and related conditions. NCBI+1

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The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: September 24, 2025.

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