Full Report

Format

Full Report
Summary (Text)
Summary (XML)

Send to:

Choose Destination

File
Clipboard
Collections

Aicardi-Goutieres syndrome 8(AGS8)

MedGen UID:: 1790409
•Concept ID:: C5551352
•: Disease or Syndrome

Synonyms:	AGS8; AICARDI-GOUTIERES SYNDROME 8

Gene (location): Gene(s) directly associated with this condition or phenotype.	LSM11 (5q33.3)

Monarch Initiative:	MONDO:0030361
OMIM®:	619486

Definition

Aicardi-Goutieres syndrome-8 (AGS8) is a type I interferonopathy characterized by severe developmental delay and progressive neurologic deterioration ending in premature death. Brain imaging shows diffusely abnormal white matter, severe cerebral atrophy, and intracranial calcification (Uggenti et al., 2020). For a general phenotypic description and discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750). [from OMIM]

Clinical features

From HPO

Hypoplastic male external genitalia

MedGen UID:: 338952
•Concept ID:: C1852534
•: Finding

Underdevelopment of part or all of the male external reproductive organs (which include the penis, the scrotum and the urethra).

See: Feature record | Search on this feature

Seizure

MedGen UID:: 20693
•Concept ID:: C0036572
•: Sign or Symptom

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

See: Feature record | Search on this feature

CSF pleocytosis

MedGen UID:: 56247
•Concept ID:: C0151857
•: Disease or Syndrome

An increased white blood cell count in the cerebrospinal fluid.

See: Feature record | Search on this feature

Cerebral atrophy

MedGen UID:: 116012
•Concept ID:: C0235946
•: Disease or Syndrome

Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.

See: Feature record | Search on this feature

Abnormal cerebral white matter morphology

MedGen UID:: 181756
•Concept ID:: C0948163
•: Pathologic Function

An abnormality of the cerebral white matter.

See: Feature record | Search on this feature

Severe global developmental delay

MedGen UID:: 332436
•Concept ID:: C1837397
•: Finding

A severe delay in the achievement of motor or mental milestones in the domains of development of a child.

See: Feature record | Search on this feature

Irritability

MedGen UID:: 397841
•Concept ID:: C2700617
•: Mental Process

A proneness to anger, i.e., a tendency to become easily bothered or annoyed.

See: Search on this feature

Basal ganglia calcification

MedGen UID:: 234651
•Concept ID:: C1389280
•: Pathologic Function

The presence of calcium deposition affecting one or more structures of the basal ganglia.

See: Feature record | Search on this feature

Nystagmus

MedGen UID:: 45166
•Concept ID:: C0028738
•: Disease or Syndrome

Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

See: Feature record | Search on this feature

Show all Hide all

Abnormality of the eye
- Nystagmus
Abnormality of the genitourinary system
- Hypoplastic male external genitalia
Abnormality of the musculoskeletal system
- Basal ganglia calcification
Abnormality of the nervous system

Professional guidelines

PubMed

Monogenic interferon-mediated diseases: novel phenotype and genotype characteristics from a Saudi population.

Al-Saleem A, Alansari S, Almuhaizea M, Al-Mayouf SM
Clin Exp Rheumatol 2024 Nov;42(11):2295-2302. Epub 2024 Jul 5 doi: 10.55563/clinexprheumatol/aa6drm. PMID: 38976295

Systematic analysis of genotype-phenotype variability in siblings with Aicardi Goutières Syndrome (AGS).

de Barcelos IP, Woidill S, Gavazzi F, Modesti NB, Sevagamoorthy A, Vanderver A, Adang L
Mol Genet Metab 2024 May;142(1):108346. Epub 2024 Feb 13 doi: 10.1016/j.ymgme.2024.108346. PMID: 38368708 Free PMC Article

Evaluation of X-Linked Adrenoleukodystrophy Newborn Screening in North Carolina.

Lee S, Clinard K, Young SP, Rehder CW, Fan Z, Calikoglu AS, Bali DS, Bailey DB Jr, Gehtland LM, Millington DS, Patel HS, Beckloff SE, Zimmerman SJ, Powell CM, Taylor JL
JAMA Netw Open 2020 Jan 3;3(1):e1920356. doi: 10.1001/jamanetworkopen.2019.20356. PMID: 32003821 Free PMC Article

See all (3)

Recent clinical studies

Etiology

Systemic complications of Aicardi Goutières syndrome using real-world data.

Peixoto de Barcelos I, Jan AK, Modesti N, Woidill S, Gavazzi F, Isaacs D, D'Aiello R, Sevagamoorthy A, Charlton L, Pizzino A, Schmidt J, van Haren K, Keller S, Eichler F, Emrick LT, Fraser JL, Shults J, Vanderver A, Adang LA
Mol Genet Metab 2024 Sep-Oct;143(1-2):108578. Epub 2024 Sep 15 doi: 10.1016/j.ymgme.2024.108578. PMID: 39332260

Nonverbal Cognitive Skills in Children With Aicardi Goutières Syndrome.

Gavazzi F, Vaia Y, Woidill S, Formanowski B, Peixoto de Barcelos I, Sevagamoorthy A, Modesti NB, Charlton L, Cusack SV, Vincent A, D'Aiello R, Jawad A, Galli J, Varesio C, Fazzi E, Orcesi S, Glanzman AM, Lorch S, DeMauro SB, Guez-Barber D, Waldman AT, Vanderver A, Adang LA
Neurology 2024 Jul 9;103(1):e209541. Epub 2024 Jun 10 doi: 10.1212/WNL.0000000000209541. PMID: 38857477 Free PMC Article

Characterization of Fine Motor and Visual Motor Skills in Aicardi-Goutières Syndrome.

Cusack SV, Gavazzi F, de Barcelos IP, Modesti NB, Woidill S, Formanowski B, DeMauro SB, Lorch S, Vincent A, Jawad AF, Estilow T, Glanzman AM, Vanderver A, Adang LA
J Child Neurol 2024 Mar;39(3-4):147-154. Epub 2024 Mar 27 doi: 10.1177/08830738241241786. PMID: 38532733 Free PMC Article

Computational Insights into the Structural Dynamics of MDA5 Variants Associated with Aicardi-Goutières Syndrome and Singleton-Merten Syndrome.

Gosu V, Sasidharan S, Saudagar P, Lee HK, Shin D
Biomolecules 2021 Aug 21;11(8) doi: 10.3390/biom11081251. PMID: 34439917 Free PMC Article

Late-Onset Aicardi-Goutières Syndrome: A Characterization of Presenting Clinical Features.

Piccoli C, Bronner N, Gavazzi F, Dubbs H, De Simone M, De Giorgis V, Orcesi S, Fazzi E, Galli J, Masnada S, Tonduti D, Varesio C, Vanderver A, Vossough A, Adang L
Pediatr Neurol 2021 Feb;115:1-6. Epub 2020 Nov 2 doi: 10.1016/j.pediatrneurol.2020.10.012. PMID: 33307271 Free PMC Article

See all (20)

Diagnosis

Intracerebral large artery disease in Aicardi-Goutières syndrome with TREX1 mutation: a case report.

Wu CC, Peng SS, Lee WT
Neurol Sci 2020 Nov;41(11):3353-3356. Epub 2020 Jun 10 doi: 10.1007/s10072-020-04516-0. PMID: 32524323

Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.

de Jesus AA, Hou Y, Brooks S, Malle L, Biancotto A, Huang Y, Calvo KR, Marrero B, Moir S, Oler AJ, Deng Z, Montealegre Sanchez GA, Ahmed A, Allenspach E, Arabshahi B, Behrens E, Benseler S, Bezrodnik L, Bout-Tabaku S, Brescia AC, Brown D, Burnham JM, Caldirola MS, Carrasco R, Chan AY, Cimaz R, Dancey P, Dare J, DeGuzman M, Dimitriades V, Ferguson I, Ferguson P, Finn L, Gattorno M, Grom AA, Hanson EP, Hashkes PJ, Hedrich CM, Herzog R, Horneff G, Jerath R, Kessler E, Kim H, Kingsbury DJ, Laxer RM, Lee PY, Lee-Kirsch MA, Lewandowski L, Li S, Lilleby V, Mammadova V, Moorthy LN, Nasrullayeva G, O'Neil KM, Onel K, Ozen S, Pan N, Pillet P, Piotto DG, Punaro MG, Reiff A, Reinhardt A, Rider LG, Rivas-Chacon R, Ronis T, Rösen-Wolff A, Roth J, Ruth NM, Rygg M, Schmeling H, Schulert G, Scott C, Seminario G, Shulman A, Sivaraman V, Son MB, Stepanovskiy Y, Stringer E, Taber S, Terreri MT, Tifft C, Torgerson T, Tosi L, Van Royen-Kerkhof A, Wampler Muskardin T, Canna SW, Goldbach-Mansky R
J Clin Invest 2020 Apr 1;130(4):1669-1682. doi: 10.1172/JCI129301. PMID: 31874111 Free PMC Article

Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.

Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GM, Gornall HL, Oojageer A, Anderson B, Pizzino A, Helman G, Abdel-Hamid MS, Abdel-Salam GM, Ackroyd S, Aeby A, Agosta G, Albin C, Allon-Shalev S, Arellano M, Ariaudo G, Aswani V, Babul-Hirji R, Baildam EM, Bahi-Buisson N, Bailey KM, Barnerias C, Barth M, Battini R, Beresford MW, Bernard G, Bianchi M, Billette de Villemeur T, Blair EM, Bloom M, Burlina AB, Carpanelli ML, Carvalho DR, Castro-Gago M, Cavallini A, Cereda C, Chandler KE, Chitayat DA, Collins AE, Sierra Corcoles C, Cordeiro NJ, Crichiutti G, Dabydeen L, Dale RC, D'Arrigo S, De Goede CG, De Laet C, De Waele LM, Denzler I, Desguerre I, Devriendt K, Di Rocco M, Fahey MC, Fazzi E, Ferrie CD, Figueiredo A, Gener B, Goizet C, Gowrinathan NR, Gowrishankar K, Hanrahan D, Isidor B, Kara B, Khan N, King MD, Kirk EP, Kumar R, Lagae L, Landrieu P, Lauffer H, Laugel V, La Piana R, Lim MJ, Lin JP, Linnankivi T, Mackay MT, Marom DR, Marques Lourenço C, McKee SA, Moroni I, Morton JE, Moutard ML, Murray K, Nabbout R, Nampoothiri S, Nunez-Enamorado N, Oades PJ, Olivieri I, Ostergaard JR, Pérez-Dueñas B, Prendiville JS, Ramesh V, Rasmussen M, Régal L, Ricci F, Rio M, Rodriguez D, Roubertie A, Salvatici E, Segers KA, Sinha GP, Soler D, Spiegel R, Stödberg TI, Straussberg R, Swoboda KJ, Suri M, Tacke U, Tan TY, te Water Naude J, Wee Teik K, Thomas MM, Till M, Tonduti D, Valente EM, Van Coster RN, van der Knaap MS, Vassallo G, Vijzelaar R, Vogt J, Wallace GB, Wassmer E, Webb HJ, Whitehouse WP, Whitney RN, Zaki MS, Zuberi SM, Livingston JH, Rozenberg F, Lebon P, Vanderver A, Orcesi S, Rice GI
Am J Med Genet A 2015 Feb;167A(2):296-312. Epub 2015 Jan 16 doi: 10.1002/ajmg.a.36887. PMID: 25604658 Free PMC Article

Aicardi-Goutières syndrome (AGS).

Stephenson JB
Eur J Paediatr Neurol 2008 Sep;12(5):355-8. Epub 2008 Mar 14 doi: 10.1016/j.ejpn.2007.11.010. PMID: 18343173

Clinical and molecular phenotype of Aicardi-Goutieres syndrome.

Rice G, Patrick T, Parmar R, Taylor CF, Aeby A, Aicardi J, Artuch R, Montalto SA, Bacino CA, Barroso B, Baxter P, Benko WS, Bergmann C, Bertini E, Biancheri R, Blair EM, Blau N, Bonthron DT, Briggs T, Brueton LA, Brunner HG, Burke CJ, Carr IM, Carvalho DR, Chandler KE, Christen HJ, Corry PC, Cowan FM, Cox H, D'Arrigo S, Dean J, De Laet C, De Praeter C, Dery C, Ferrie CD, Flintoff K, Frints SG, Garcia-Cazorla A, Gener B, Goizet C, Goutieres F, Green AJ, Guet A, Hamel BC, Hayward BE, Heiberg A, Hennekam RC, Husson M, Jackson AP, Jayatunga R, Jiang YH, Kant SG, Kao A, King MD, Kingston HM, Klepper J, van der Knaap MS, Kornberg AJ, Kotzot D, Kratzer W, Lacombe D, Lagae L, Landrieu PG, Lanzi G, Leitch A, Lim MJ, Livingston JH, Lourenco CM, Lyall EG, Lynch SA, Lyons MJ, Marom D, McClure JP, McWilliam R, Melancon SB, Mewasingh LD, Moutard ML, Nischal KK, Ostergaard JR, Prendiville J, Rasmussen M, Rogers RC, Roland D, Rosser EM, Rostasy K, Roubertie A, Sanchis A, Schiffmann R, Scholl-Burgi S, Seal S, Shalev SA, Corcoles CS, Sinha GP, Soler D, Spiegel R, Stephenson JB, Tacke U, Tan TY, Till M, Tolmie JL, Tomlin P, Vagnarelli F, Valente EM, Van Coster RN, Van der Aa N, Vanderver A, Vles JS, Voit T, Wassmer E, Weschke B, Whiteford ML, Willemsen MA, Zankl A, Zuberi SM, Orcesi S, Fazzi E, Lebon P, Crow YJ
Am J Hum Genet 2007 Oct;81(4):713-25. Epub 2007 Sep 4 doi: 10.1086/521373. PMID: 17846997 Free PMC Article

See all (30)

Therapy

Systemic complications of Aicardi Goutières syndrome using real-world data.

Children With Type I Interferonopathy: Commonalities and Diversities in a Large Patient Cohort.

Haslak F, Kilic H, Sahin S, Hotaman B, Cebi NM, Yildiz M, Adrovic A, Gunalp A, Konte EK, Aslan E, Gul U, Akay N, Zindar Y, Ulug F, Guler S, Kiykim A, Aydemir S, Barut K, Saltik S, Cokugras HC, Kasapcopur O
J Rheumatol 2024 Dec 1;51(12):1208-1217. doi: 10.3899/jrheum.2024-0294. PMID: 39089832

Characterization of Fine Motor and Visual Motor Skills in Aicardi-Goutières Syndrome.

Efficacy and safety of thalidomide in children with monogenic autoinflammatory diseases: a single-center, real-world-evidence study.

Zhang C, Yu Z, Gao S, Ma M, Gou L, Wang C, Wang L, Li J, Zhong L, Zhou Y, Wang W, Song H
Pediatr Rheumatol Online J 2023 Oct 17;21(1):124. doi: 10.1186/s12969-023-00881-0. PMID: 37848905 Free PMC Article

Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.

See all (8)

Prognosis

Systemic complications of Aicardi Goutières syndrome using real-world data.

A case report of two Moroccan patients with hereditary neurological disorders and molecular modeling study on the S72L de novo PMP22 variant.

Ait El Cadi C, Dafrallah L, Amalou G, Charif M, Charoute H, Araqi-Houssaini A, Lakhiari H, Lenaers G, Barakat A
Rev Neurol (Paris) 2023 Oct;179(8):902-909. Epub 2023 Jun 7 doi: 10.1016/j.neurol.2023.01.728. PMID: 37296061

Magnetic resonance imaging of anterior temporal lobe cysts in children: discriminating special imaging features in a particular group of diseases.

Nunes RH, Pacheco FT, da Rocha AJ
Neuroradiology 2014 Jul;56(7):569-77. Epub 2014 Apr 23 doi: 10.1007/s00234-014-1356-9. PMID: 24756164

Brain damage as detected by cDNA-microarray in the spinal fluid of patients with Aicardi-Goutieres syndrome.

Izzotti A, Fazzi E, Orcesi S, Cartiglia C, Longobardi M, Capra V, Lebon P, Cama A, Pulliero A, La Piana R, Lanzi G
Neurology 2008 Aug 19;71(8):610-2. Epub 2008 Jul 2 doi: 10.1212/01.wnl.0000313934.05965.71. PMID: 18596240

Aicardi-Goutières syndrome (AGS).

Stephenson JB
Eur J Paediatr Neurol 2008 Sep;12(5):355-8. Epub 2008 Mar 14 doi: 10.1016/j.ejpn.2007.11.010. PMID: 18343173

See all (11)

Clinical prediction guides

cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing.

Uggenti C, Lepelley A, Depp M, Badrock AP, Rodero MP, El-Daher MT, Rice GI, Dhir S, Wheeler AP, Dhir A, Albawardi W, Frémond ML, Seabra L, Doig J, Blair N, Martin-Niclos MJ, Della Mina E, Rubio-Roldán A, García-Pérez JL, Sproul D, Rehwinkel J, Hertzog J, Boland-Auge A, Olaso R, Deleuze JF, Baruteau J, Brochard K, Buckley J, Cavallera V, Cereda C, De Waele LMH, Dobbie A, Doummar D, Elmslie F, Koch-Hogrebe M, Kumar R, Lamb K, Livingston JH, Majumdar A, Lorenço CM, Orcesi S, Peudenier S, Rostasy K, Salmon CA, Scott C, Tonduti D, Touati G, Valente M, van der Linden H Jr, Van Esch H, Vermelle M, Webb K, Jackson AP, Reijns MAM, Gilbert N, Crow YJ
Nat Genet 2020 Dec;52(12):1364-1372. Epub 2020 Nov 23 doi: 10.1038/s41588-020-00737-3. PMID: 33230297

Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.

RNA degradation in antiviral immunity and autoimmunity.

Rigby RE, Rehwinkel J
Trends Immunol 2015 Mar;36(3):179-88. Epub 2015 Feb 20 doi: 10.1016/j.it.2015.02.001. PMID: 25709093 Free PMC Article

Aicardi-Goutières syndrome (AGS).

Stephenson JB
Eur J Paediatr Neurol 2008 Sep;12(5):355-8. Epub 2008 Mar 14 doi: 10.1016/j.ejpn.2007.11.010. PMID: 18343173

Clinical and molecular phenotype of Aicardi-Goutieres syndrome.

See all (33)