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IEMbase 0776: IFIH1-related MDA5 superactivity

Scope

Field Value
IEMbase ID 776
Nosology 16.3.08.01
Nosology code IEM0033
Gene IFIH1
External IDs OMIM:615846; ORPHA:85191
Generated mapping AMBIGUOUS; Aicardi_Goutieres_Syndrome and subtype Aicardi-Goutieres syndrome 7
Candidate DisMech targets Aicardi_Goutieres_Syndrome.yaml subtype Aicardi-Goutieres syndrome 7
Review date 2026-07-08

IEMbase phenotype signal

IEMbase labels this autosomal dominant record as IFIH1-related MDA5 superactivity, with alternate name Aicardi-Goutieres syndrome type 7. The source signal includes cognitive dysfunction, dystonia, seizures, hepatosplenomegaly, sterile pyrexia, sleep disturbance, chilblains, feeding difficulty, intracerebral calcifications, cerebral atrophy, leukodystrophy, microcephaly, spasticity, exaggerated startle, irritability, and an optional isolated spastic paraparesis row. Laboratory rows include transaminases, CSF neopterin, CSF lymphocytes, CSF interferon-alpha, interferon-stimulated gene signature, autoantibodies, platelets, and neonatal C26:0 fatty acid.

DisMech phenotype coverage

Aicardi_Goutieres_Syndrome.yaml has an explicit Aicardi-Goutieres syndrome 7 subtype with IFIH1 and MONDO:0014367. The local AGS entry captures heterozygous IFIH1 gain-of-function, abnormal MDA5 sensing, type I interferon signaling, and the broad shared AGS phenotype set: neurodevelopmental impairment, regression, spasticity, dystonia, seizures, microcephaly, leukodystrophy, cerebral calcification, brain atrophy, chilblains, fevers, hepatosplenomegaly, CSF lymphocytosis, increased CSF interferon-alpha, and autoimmunity.

Concordance and completeness

Judgement: exact subtype coverage; generated ambiguity reflects local disease-level and subtype-level matches.

The gene, dominant inheritance, OMIM identity, subtype identity, and core interferonopathy phenotype are concordant. IEMbase adds several explicit phenotype prompts that are not independently represented in the local phenotype list, especially isolated spastic paraparesis, feeding difficulty, sleep disturbance, startle response, and CSF neopterin.

Curation actions

  • Treat Aicardi_Goutieres_Syndrome.yaml subtype Aicardi-Goutieres syndrome 7 as exact local coverage for IEMbase 0776.
  • Preserve IFIH1 gain-of-function and autosomal dominant inheritance as subtype-specific distinguishing features.
  • Review isolated spastic paraparesis and CSF neopterin as possible completeness additions before changing the KB.