IllnessAicardi-Goutières syndrome, differential diagnosis

NGS +

Aicardi-Goutières syndrome is a disorder that primarily affects the brain, immune system and skin. Most newborns with the syndrome are asymptomatic; about 20% are born with hepatosplenomegaly, elevated liver enzymes, thrombocytopenia and neurologic abnormalities. This constellation is sometimes considered to reflect congenital infection. Within the first year of life, most children with Aicardi-Goutières syndrome experience an episode of severe encephalopathy lasting several months. The growth of the brain and skull slows, leading to microcephaly with inflammation and tissue damage in the central nervous system. This phase leads to permanent and severe neurological damage with mental retardation via leukodystrophy and calcification. Spasticity, dystonia and hypotonia develop in the trunk. Some patients have features of autoimmune disease resembling systemic lupus erythematosus, ~40% have chilblains. Visual disturbances, joint stiffness and oral ulcers may occur. Because of the severe neurologic problems that usually accompany, most patients do not survive childhood. Mutations in multiple genes can cause Aicardi-Goutières syndrome, and it can also have different inheritance patterns, in most cases an autosomal recessive and rarely a dominant pattern. The molecular genetic diagnostic yield reaches 99%, virtually always confirming the carefully established clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1475/

• Alias: Encephalopathy with basal ganglia calcification
• Alias: Encephalopathy with intracranial calcification + chron. lymphocytosis of cerebrospinal fluid
• Alias: Encephalopathy, familial infantile, intracranial calcification, chronic liquor lymphocytosis
• Allelic: Cerebrooculofacioskeletal syndrome 1 (ERCC6)
• Allelic: Chilblain lupus (TREX1)
• Allelic: Chilblain lupus 2 (SAMHD1)
• Allelic: De Sanctis-Cacchione syndrome (ERCC6)
• Allelic: Dyschromatosis symmetrica hereditaria (ADAR1)
• Allelic: Lung cancer, susceptibility to (ERCC6)
• Allelic: Macular degeneration, age-related, susceptibility to, 5 (ERCC6)
• Allelic: Ovarioleukodystrophy (EIF2B2, EIF2B4, EIF2B5)
• Allelic: Premature ovarian failure 11 (ERCC6)
• Allelic: Spastic paraplegia 2, XL (PLP1)
• Allelic: Systemic lupus erythematosus, susceptibility to (TREX1)
• Allelic: UV-sensitive syndrome 1 (ERCC6)
• Allelic: UV-sensitive syndrome 2 (ERCC8)
• Allelic: Vasculopathy, retinal, with cerebral leukodystrophy (TREX1)
• Aicardi-Goutieres syndrome 1, AD + AR (TREX1)
• Aicardi-Goutieres syndrome 2 (RNASEH2B)
• Aicardi-Goutieres syndrome 3 (RNASEH2C)
• Aicardi-Goutieres syndrome 4 (RNASEH2A)
• Aicardi-Goutieres syndrome 5 (SAMHD1)
• Aicardi-Goutieres syndrome 6 (ADAR1)
• Aicardi-Goutieres syndrome 7 (IFIH1)
• Alexander disease (GFAP)
• Cerebroretinal microangiopathy with calcifications + cysts (CTC1)
• Cockayne syndrome, type A (ERCC8)
• Cockayne syndrome, type B (ERCC6)
• Dyskeratosis congenita, AD 3 (TINF2)
• Dyskeratosis congenita, XL; Hoyeraal-Hreidarsson syndrome (DKC1)
• Immunodeficiency 38 (ISG15)
• Leukoencephalopathy with vanishing white matter (EIF2B1)
• Leukoencephalopathy with vanishing white matter (EIF2B2)
• Leukoencephalopathy with vanishing white matter (EIF2B3)
• Leukoencephalopathy with vanishing white matter (EIF2B4)
• Leukoencephalopathy with vanishing white matter (EIF2B5)
• Megalencephalic leukoencephalopathy with subcortical cysts (MLC1)
• Megalencephalic leukoencephalopathy with subcortical cysts 2A (HEPACAM)
• Megalencephalic leukoencephalopathy, subcort. cysts 2B, remitting, with/-out ment. retard. (HEPACAM)
• Pelizaeus-Merzbacher disease (PLP1)
• Proteasome-associated autoinflammatory syndrome 1 + digenic forms (PSMB8)
• Pseudo-TORCH syndrome 1 (OCLN)
• Revesz syndrome (TINF2)
• STING-associated vasculopathy, infantile-onset (STING1 syn. TMEM173)
• Singleton-Merten syndrome 1 (IFIH1)
• Singleton-Merten syndrome 2 (DDX58)
• Spondyloenchondrodysplasia with immune dysregulation (ACP5)