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Pachygyria-intellectual disability-epilepsy syndrome

MedGen UID:
333107
Concept ID:
C1838491
Disease or Syndrome
Synonyms: Kuzniecky syndrome; PACHYGYRIA WITH IMPAIRED INTELLECTUAL DEVELOPMENT, SEIZURES, AND ARACHNOID CYSTS; Pachygyria with mental retardation and seizures; Pachygyria, mental retardation and epilepsy
SNOMED CT: Pachygyria, intellectual disability, epilepsy syndrome (763861000); Kuzniecky syndrome (763861000)
 
Monarch Initiative: MONDO:0010840
OMIM®: 600176
Orphanet: ORPHA2798

Definition

This autosomal recessive neurodevelopmental disorder is characterized by pachygyria, impaired intellectual development, seizures, and diffuse localization of arachnoid cysts. It most likely represents a neuronal migration disorder within the lissencephaly spectrum (summary by Guzel et al., 2007). [from OMIM]

Clinical features

From HPO
Arachnoid cyst
MedGen UID:
86860
Concept ID:
C0078981
Disease or Syndrome
An extra-parenchymal and intra-arachnoidal collection of fluid with a composition similar to that of cerebrospinal fluid.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Atypical absence seizure
MedGen UID:
108888
Concept ID:
C0595948
Disease or Syndrome
An atypical absence seizure is a type of generalized non-motor (absence) seizure characterized by interruption of ongoing activities and reduced responsiveness. In comparison to a typical absence seizure, changes in tone may be more pronounced, onset and/or cessation may be less abrupt, and the duration of the ictus and post-ictal recovery may be longer. Although not always available, an EEG often demonstrates slow (<3 Hz), irregular, generalized spike-wave activity.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Profound static encephalopathy
MedGen UID:
870497
Concept ID:
C4024944
Disease or Syndrome
Pachygyria
MedGen UID:
504794
Concept ID:
CN001193
Finding
Pachygyria is a malformation of cortical development with abnormally wide gyri with sulci 1,5-3 cm apart and abnormally thick cortex measuring more than 5 mm (radiological definition). See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly.
Abnormality of the skeletal system
MedGen UID:
867418
Concept ID:
C4021790
Anatomical Abnormality
An abnormality of the skeletal system.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPachygyria-intellectual disability-epilepsy syndrome
Follow this link to review classifications for Pachygyria-intellectual disability-epilepsy syndrome in Orphanet.

Professional guidelines

PubMed

van Karnebeek CD, Bowden K, Berry-Kravis E
Pediatr Neurol 2016 Dec;65:1-13. Epub 2016 Jul 26 doi: 10.1016/j.pediatrneurol.2016.07.010. PMID: 27697313
Granild Bie Mertz L, Christensen R, Vogel I, Hertz JM, Østergaard JR
Res Dev Disabil 2016 Sep;56:177-82. doi: 10.1016/j.ridd.2016.06.002. PMID: 27323320
Nizon M, Andrieux J, Rooryck C, de Blois MC, Bourel-Ponchel E, Bourgois B, Boute O, David A, Delobel B, Duban-Bedu B, Giuliano F, Goldenberg A, Grotto S, Héron D, Karmous-Benailly H, Keren B, Lacombe D, Lapierre JM, Le Caignec C, Le Galloudec E, Le Merrer M, Le Moing AG, Mathieu-Dramard M, Nusbaum S, Pichon O, Pinson L, Raoul O, Rio M, Romana S, Roubertie A, Colleaux L, Turleau C, Vekemans M, Nabbout R, Malan V
Am J Med Genet A 2015 Jan;167A(1):111-22. Epub 2014 Nov 25 doi: 10.1002/ajmg.a.36807. PMID: 25425167

Recent clinical studies

Etiology

Ebrahimi-Fakhari D
Neuropediatrics 2018 Feb;49(1):18-25. Epub 2017 Nov 7 doi: 10.1055/s-0037-1608652. PMID: 29112993
Skopkova M, Hennig F, Shin BS, Turner CE, Stanikova D, Brennerova K, Stanik J, Fischer U, Henden L, Müller U, Steinberger D, Leshinsky-Silver E, Bottani A, Kurdiova T, Ukropec J, Nyitrayova O, Kolnikova M, Klimes I, Borck G, Bahlo M, Haas SA, Kim JR, Lotspeich-Cole LE, Gasperikova D, Dever TE, Kalscheuer VM
Hum Mutat 2017 Apr;38(4):409-425. Epub 2017 Jan 23 doi: 10.1002/humu.23170. PMID: 28055140Free PMC Article
van Karnebeek CD, Bowden K, Berry-Kravis E
Pediatr Neurol 2016 Dec;65:1-13. Epub 2016 Jul 26 doi: 10.1016/j.pediatrneurol.2016.07.010. PMID: 27697313
Granild Bie Mertz L, Christensen R, Vogel I, Hertz JM, Østergaard JR
Res Dev Disabil 2016 Sep;56:177-82. doi: 10.1016/j.ridd.2016.06.002. PMID: 27323320
Leen WG, Taher M, Verbeek MM, Kamsteeg EJ, van de Warrenburg BP, Willemsen MA
J Neurol 2014 Mar;261(3):589-99. Epub 2014 Jan 12 doi: 10.1007/s00415-014-7240-z. PMID: 24413642

Diagnosis

Solazzi R, Fiorini E, Parrini E, Guerrini R, Bernardina BD, Nardocci N, Cantalupo G
Epileptic Disord 2021 Oct 1;23(5):745-748. doi: 10.1684/epd.2021.1328. PMID: 34583915
Scheffer IE, Nabbout R
Epilepsia 2019 Dec;60 Suppl 3:S17-S24. doi: 10.1111/epi.16386. PMID: 31904117
van Karnebeek CD, Bowden K, Berry-Kravis E
Pediatr Neurol 2016 Dec;65:1-13. Epub 2016 Jul 26 doi: 10.1016/j.pediatrneurol.2016.07.010. PMID: 27697313
Ebrahimi-Fakhari D, Saffari A, Wahlster L, Lu J, Byrne S, Hoffmann GF, Jungbluth H, Sahin M
Brain 2016 Feb;139(Pt 2):317-37. Epub 2015 Dec 29 doi: 10.1093/brain/awv371. PMID: 26715604Free PMC Article
Leen WG, Taher M, Verbeek MM, Kamsteeg EJ, van de Warrenburg BP, Willemsen MA
J Neurol 2014 Mar;261(3):589-99. Epub 2014 Jan 12 doi: 10.1007/s00415-014-7240-z. PMID: 24413642

Therapy

Banfi P, Coll M, Oliva A, Alcalde M, Striano P, Mauri M, Princiotta L, Campuzano O, Versino M, Brugada R
Gene 2020 Sep 5;754:144847. Epub 2020 Jun 9 doi: 10.1016/j.gene.2020.144847. PMID: 32531456
Hausman-Kedem M, Menascu S, Greenstein Y, Fattal-Valevski A
Epilepsy Res 2020 Jul;163:106325. Epub 2020 Apr 2 doi: 10.1016/j.eplepsyres.2020.106325. PMID: 32289570

Prognosis

Bonardi CM, Bayat A, Madsen CG, Hammer TB, Reale C, Gardella E, Marjanovic D, Beniczky S, Møller RS, Rubboli G
Epileptic Disord 2022 Jun 1;24(3):577-582. doi: 10.1684/epd.2022.1423. PMID: 35770758
Prat D, Katowitz WR, Strong A, Katowitz JA
Ophthalmic Genet 2021 Apr;42(2):186-188. Epub 2021 Jan 3 doi: 10.1080/13816810.2020.1868012. PMID: 33393407
He X, Shen H, Fu H, Feng C, Liu Z, Jin Y, Mao J
BMC Pediatr 2020 Jul 2;20(1):327. doi: 10.1186/s12887-020-02205-7. PMID: 32616040Free PMC Article
Shoubridge C, Jackson M, Grinton B, Berkovic SF, Scheffer IE, Huskins S, Thomas A, Ware T
Am J Med Genet A 2019 Aug;179(8):1483-1490. Epub 2019 May 30 doi: 10.1002/ajmg.a.61216. PMID: 31145546
Leen WG, Taher M, Verbeek MM, Kamsteeg EJ, van de Warrenburg BP, Willemsen MA
J Neurol 2014 Mar;261(3):589-99. Epub 2014 Jan 12 doi: 10.1007/s00415-014-7240-z. PMID: 24413642

Clinical prediction guides

Sleyp Y, Valenzuela I, Accogli A, Ballon K, Ben-Zeev B, Berkovic SF, Broly M, Callaerts P, Caylor RC, Charles P, Chatron N, Cohen L, Coppola A, Cordeiro D, Cuccurullo C, Cuscó I, Janette diMonda, Duran-Romaña R, Ekhilevitch N, Fernández-Alvarez P, Gordon CT, Isidor B, Keren B, Lesca G, Maljaars J, Mercimek-Andrews S, Morrow MM, Muir AM; University of Washington Center for Mendelian Genomics, Rousseau F, Salpietro V, Scheffer IE, Schnur RE, Schymkowitz J, Souche E, Steyaert J, Stolerman ES, Vengoechea J, Ville D, Washington C, Weiss K, Zaid R, Sadleir LG, Mefford HC, Peeters H
Genet Med 2022 Dec;24(12):2464-2474. Epub 2022 Oct 11 doi: 10.1016/j.gim.2022.08.020. PMID: 36214804
de Boer E, Ockeloen CW, Matalonga L, Horvath R; Solve-RD SNV-indel working group, Rodenburg RJ, Coenen MJH, Janssen M, Henssen D, Gilissen C, Steyaert W, Paramonov I; Solve-RD-DITF-ITHACA, Trimouille A, Kleefstra T, Verloes A, Vissers LELM
Eur J Hum Genet 2021 Sep;29(9):1359-1368. Epub 2021 Jun 1 doi: 10.1038/s41431-021-00900-2. PMID: 34075211Free PMC Article
Rotaru DC, Mientjes EJ, Elgersma Y
Neuroscience 2020 Oct 1;445:172-189. Epub 2020 Feb 21 doi: 10.1016/j.neuroscience.2020.02.017. PMID: 32088294
Bonanni P, Casellato S, Fabbro F, Negrin S
Am J Med Genet A 2017 Oct;173(10):2753-2757. Epub 2017 Aug 16 doi: 10.1002/ajmg.a.38373. PMID: 28815953
Rocha H, Sampaio M, Rocha R, Fernandes S, Leão M
Eur J Med Genet 2016 Sep;59(9):478-82. Epub 2016 May 31 doi: 10.1016/j.ejmg.2016.05.017. PMID: 27255693

Recent systematic reviews

Leen WG, Taher M, Verbeek MM, Kamsteeg EJ, van de Warrenburg BP, Willemsen MA
J Neurol 2014 Mar;261(3):589-99. Epub 2014 Jan 12 doi: 10.1007/s00415-014-7240-z. PMID: 24413642

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