(Aicardi-Goutieres syndrome, microcephaly-intracranial calcifications syndrome, pseudo-TORCH, Cree encephalitis)

Very rare. Autosomal recessive or dominant transmission of a mutation in one of the genes described below.

Identified types:

• AGS1[MIM 225 750]: mutation of the TREX1 gene (3p21.31) (35 %)coding for a 3' → 5' exonuclease (Cree encephalitis)
• AGS2 [MIM 610 181]: mutation of the RNASEH2B gene (13q14.3)(45 %)
• AGS3 [MIM 610 329] : mutation of the RNASEH2C gene (11q13.1) (15 %)
• AGS4 [MIM 610 333] : mutation of the RNASEH2A gene (19p13.13) (<  5 %)
• AGS5 [MIM 612 952] : mutation of the SAMHD1 gene (20q11.23) (≈ 10 %)
• AGS6 [MIM 615 010] : mutation of the ADAR1 gene (1q21.3)
• AGS7 [MIM 615 845] : mutation of the IFIH1 gene (2q24)
• AGS8 [MIM 619 486]: mutation of the LSM11 gene (5q33)
• AGS9 [MIM 619 487] : mutation of the RNU7-1 gene (12q13)

The mutations in the TREX1  (25 %), RNASEH2C (14 %) and RNASEH2A (4 %) genes produce a severe phenotype while the mutations in the RNASEH2B gene (45 %) are responsible for less severe forms.

Encephalopathy, characterized by hypsarrhythmia (flexion spasms)  with a typical EEG tracing, a complex cerebral malformation (including agenesis or hypoplasia of the corpus callosum), a chorioretinopathy (qualified as lacunar) and profound mental retardation. 

Clinical presentation: 

-        cerebral calcifications, 

-        leukodystrophy, 

-        cerebral atrophy,

-        progressive microcephaly, 

-        chronic lymphocytosis and increased levels of interferon alpha (alpha - INF) and neopterin in the CSF. 

-        sometimes vertebral anomalies, hepatosplenomegaly and thrombopenia

-        the facial morphology is particular: prominent jaw, upturned nose. 

Different forms:

-        neonatal form (20 %) : the clinical picture suggests a severe neonatal infection  (TORCH type)  with anemia, thrombocytopenia, microcephaly. The mortality is high.

-        infantile form (80 %): after a period of normal development, onset of a subacute encephalopathy, progressing to refractory epilepsy with mental and motor regression, severe spasticity,  microcephaly,  blindness. It is an inflammatory process caused by a dysregulation of the interferon production. In addition, an auto-inflammatory process can lead to diabetes, hypothyroidism, cardiomyopathy, frostbite-like skin lesions (pernio) or disseminated erythematous lupus. Severe forms usually result in death, generally before 10 years of age.

Anesthetic implications: 

Refractory epilepsy, profound mental retardation, cerebral malformations. Endocrinologic evaluation and echocardiography. Risk of difficult mask ventilation and intubation. Difficult peripheral venous access caused by the limb contractures. Prevention of hypothermia.

References : 

-         Gooden CK, Pate VA, Kavee R. 
Anesthetic management of a child with Aicardi syndrome. 
Pediatr Anesth 2005; 15: 172-3.

-         Mayhew J. 
Anesthesia in a child with Aicardi syndrome . 
Pediatr Anesth 2007; 17: 1223. 

-        Salik I, Catanzaro DO, Abramowicz A.
Novel manifestation of Aicardi-Goutières syndrome : temporomandibular joint ankylosis.
J Clin Anesth 2019 ; 56 :58-9.

-        Swenson Schalkwyk AK, Agarwal R.
Anesthesia for a patient with Aicardi-Goutières syndrome : a first case report.
A&A Practice 2021 ;15 : e1410

Updated: Octobre 2021