Clinical Guidance

In its most characteristic form, Aicardi-Goutires syndrome (AGS) can be considered an early-onset encephalopathy associated with significant intellectual and physical disability. Pregnancy, delivery, and the neonatal period are normal in approximately 80% of infants with Aicardi-Goutires syndrome (AGS) . However, brain calcifications can be identified in utero and 20% of cases, mainly those caused by biallelic pathogenic variants in TREX1, present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture reminiscent of congenital infection. All other affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development.

Source: GeneReviews — "Aicardi-Goutires Syndrome"

Differential Diagnosis

Calcification of the basal ganglia is a nonspecific finding seen in many diseases. However, in the context of an early-onset encephalopathy, conditions to consider include the following:

• TORCH congenital infections are the most common conditions in the differential and the most important to rule out because misdiagnosis would result in erroneous counseling as to risk of recurrence.

Note: Other congenital infections, such as those associated with Zika and HIV, should also be considered in the differential diagnosis.

Source: GeneReviews — "Aicardi-Goutires Syndrome"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with Aicardi-Goutires syndrome (AGS), the following evaluations are recommended:

• Developmental assessment

• Assessment of feeding and nutritional status

• Ophthalmologic examination

• EEG to evaluate for seizures, if suspected

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

The following are appropriate:

• Chest physiotherapy and vigorous treatment of respiratory complications

• Attention to diet and method of feeding to assure adequate caloric intake

• Management of seizures using standard protocols

Surveillance

Surveillance includes the following:

• Monitoring for signs of diabetes insipidus in the neonatal period

• Assessment for glaucoma at least for the first few years of life

• Monitoring of the spine for the development of scoliosis

• Monitoring for signs of insulin-dependent diabetes mellitus and hypothyroidism

Evaluation of Relatives at Risk

See for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Research into the role of immunosuppressive agents in the treatment of AGS is ongoing . Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Other

Corticosteroids can lower the CSF concentration of interferon [PG Barth 2003, personal communication]; the clinical benefit of such t...

Source: GeneReviews — "Aicardi-Goutires Syndrome"

Therapies Under Investigation

Research into the role of immunosuppressive agents in the treatment of AGS is ongoing . Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Aicardi-Goutires Syndrome"