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Microcephaly, epilepsy, and diabetes syndrome 1(MEDS1)

MedGen UID:: 988370
•Concept ID:: CN305347
•: Disease or Syndrome

Synonym:	MEDS1

Gene (location): Gene(s) directly associated with this condition or phenotype.	IER3IP1 (18q21.1)

Monarch Initiative:	MONDO:0031481
OMIM®:	614231

Definition

Microcephaly, epilepsy, and diabetes syndrome-1 (MEDS1) is an autosomal recessive neurodevelopmental disorder characterized by microcephaly, simplified gyral pattern, severe epilepsy, and infantile diabetes (summary by Poulton et al., 2011). Genetic Heterogeneity of Microcephaly, Epilepsy, and Diabetes Syndrome MEDS2 (619278) is caused by mutation in the YIPF5 gene (611483) on chromosome 5q31. [from OMIM]

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVMicrocephaly, epilepsy, and diabetes syndrome
- CROGVMicrocephaly, epilepsy, and diabetes syndrome 1
- CROGVMicrocephaly, epilepsy, and diabetes syndrome 2

Cerebral malformation with epilepsy
- Microcephaly, epilepsy, and diabetes syndrome
  - Microcephaly, epilepsy, and diabetes syndrome 1

Recent clinical studies

Etiology

De Novo and Bi-allelic Pathogenic Variants in NARS1 Cause Neurodevelopmental Delay Due to Toxic Gain-of-Function and Partial Loss-of-Function Effects.

Manole A, Efthymiou S, O'Connor E, Mendes MI, Jennings M, Maroofian R, Davagnanam I, Mankad K, Lopez MR, Salpietro V, Harripaul R, Badalato L, Walia J, Francklyn CS, Athanasiou-Fragkouli A, Sullivan R, Desai S, Baranano K, Zafar F, Rana N, Ilyas M, Horga A, Kara M, Mattioli F, Goldenberg A, Griffin H, Piton A, Henderson LB, Kara B, Aslanger AD, Raaphorst J, Pfundt R, Portier R, Shinawi M, Kirby A, Christensen KM, Wang L, Rosti RO, Paracha SA, Sarwar MT, Jenkins D; SYNAPS Study Group, Ahmed J, Santoni FA, Ranza E, Iwaszkiewicz J, Cytrynbaum C, Weksberg R, Wentzensen IM, Guillen Sacoto MJ, Si Y, Telegrafi A, Andrews MV, Baldridge D, Gabriel H, Mohr J, Oehl-Jaschkowitz B, Debard S, Senger B, Fischer F, van Ravenwaaij C, Fock AJM, Stevens SJC, Bähler J, Nasar A, Mantovani JF, Manzur A, Sarkozy A, Smith DEC, Salomons GS, Ahmed ZM, Riazuddin S, Riazuddin S, Usmani MA, Seibt A, Ansar M, Antonarakis SE, Vincent JB, Ayub M, Grimmel M, Jelsig AM, Hjortshøj TD, Karstensen HG, Hummel M, Haack TB, Jamshidi Y, Distelmaier F, Horvath R, Gleeson JG, Becker H, Mandel JL, Koolen DA, Houlden H
Am J Hum Genet 2020 Aug 6;107(2):311-324. Epub 2020 Jul 31 doi: 10.1016/j.ajhg.2020.06.016. PMID: 32738225 Free PMC Article

Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases.

Perenthaler E, Nikoncuk A, Yousefi S, Berdowski WM, Alsagob M, Capo I, van der Linde HC, van den Berg P, Jacobs EH, Putar D, Ghazvini M, Aronica E, van IJcken WFJ, de Valk WG, Medici-van den Herik E, van Slegtenhorst M, Brick L, Kozenko M, Kohler JN, Bernstein JA, Monaghan KG, Begtrup A, Torene R, Al Futaisi A, Al Murshedi F, Mani R, Al Azri F, Kamsteeg EJ, Mojarrad M, Eslahi A, Khazaei Z, Darmiyan FM, Doosti M, Karimiani EG, Vandrovcova J, Zafar F, Rana N, Kandaswamy KK, Hertecant J, Bauer P, AlMuhaizea MA, Salih MA, Aldosary M, Almass R, Al-Quait L, Qubbaj W, Coskun S, Alahmadi KO, Hamad MHA, Alwadaee S, Awartani K, Dababo AM, Almohanna F, Colak D, Dehghani M, Mehrjardi MYV, Gunel M, Ercan-Sencicek AG, Passi GR, Cheema HA, Efthymiou S, Houlden H, Bertoli-Avella AM, Brooks AS, Retterer K, Maroofian R, Kaya N, van Ham TJ, Barakat TS
Acta Neuropathol 2020 Mar;139(3):415-442. Epub 2019 Dec 9 doi: 10.1007/s00401-019-02109-6. PMID: 31820119 Free PMC Article

See all (2)

Diagnosis

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

Maroofian R, Kaiyrzhanov R, Cali E, Zamani M, Zaki MS, Ferla M, Tortora D, Sadeghian S, Saadi SM, Abdullah U, Karimiani EG, Efthymiou S, Yeşil G, Alavi S, Al Shamsi AM, Tajsharghi H, Abdel-Hamid MS, Saadi NW, Al Mutairi F, Alabdi L, Beetz C, Ali Z, Toosi MB, Rudnik-Schöneborn S, Babaei M, Isohanni P, Muhammad J, Khan S, Al Shalan M, Hickey SE, Marom D, Elhanan E, Kurian MA, Marafi D, Saberi A, Hamid M, Spaull R, Meng L, Lalani S, Maqbool S, Rahman F, Seeger J, Palculict TB, Lau T, Murphy D, Mencacci NE, Steindl K, Begemann A, Rauch A, Akbas S, Aslanger AD, Salpietro V, Yousaf H, Ben-Shachar S, Ejeskär K, Al Aqeel AI, High FA, Armstrong-Javors AE, Zahraei SM, Seifi T, Zeighami J, Shariati G, Sedaghat A, Asl SN, Shahrooei M, Zifarelli G, Burglen L, Ravelli C, Zschocke J, Schatz UA, Ghavideldarestani M, Kamel WA, Van Esch H, Hackenberg A, Taylor JC, Al-Gazali L, Bauer P, Gleeson JJ, Alkuraya FS, Lupski JR, Galehdari H, Azizimalamiri R, Chung WK, Baig SM, Houlden H, Severino M
Brain 2023 Dec 1;146(12):5031-5043. doi: 10.1093/brain/awad257. PMID: 37517035 Free PMC Article

tRNA methyltransferase 10 homologue A (TRMT10A) mutation in a Chinese patient with diabetes, insulin resistance, intellectual deficiency and microcephaly.

Lin H, Zhou X, Chen X, Huang K, Wu W, Fu J, Li Y, Polychronakos C, Dong GP
BMJ Open Diabetes Res Care 2020 Oct;8(1) doi: 10.1136/bmjdrc-2020-001601. PMID: 33067246 Free PMC Article

Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.

Cnop M, Toivonen S, Igoillo-Esteve M, Salpea P
Mol Metab 2017 Sep;6(9):1024-1039. Epub 2017 Jul 12 doi: 10.1016/j.molmet.2017.06.001. PMID: 28951826 Free PMC Article

Microcephaly, epilepsy, and neonatal diabetes due to compound heterozygous mutations in IER3IP1: insights into the natural history of a rare disorder.

Shalev SA, Tenenbaum-Rakover Y, Horovitz Y, Paz VP, Ye H, Carmody D, Highland HM, Boerwinkle E, Hanis CL, Muzny DM, Gibbs RA, Bell GI, Philipson LH, Greeley SA
Pediatr Diabetes 2014 May;15(3):252-6. Epub 2013 Oct 21 doi: 10.1111/pedi.12086. PMID: 24138066 Free PMC Article

A community survey of neurological disorders in Saudi Arabia: the Thugbah study.

al Rajeh S, Bademosi O, Ismail H, Awada A, Dawodu A, al-Freihi H, Assuhaimi S, Borollosi M, al-Shammasi S
Neuroepidemiology 1993;12(3):164-78. doi: 10.1159/000110316. PMID: 8272177

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Therapy

A community survey of neurological disorders in Saudi Arabia: the Thugbah study.

al Rajeh S, Bademosi O, Ismail H, Awada A, Dawodu A, al-Freihi H, Assuhaimi S, Borollosi M, al-Shammasi S
Neuroepidemiology 1993;12(3):164-78. doi: 10.1159/000110316. PMID: 8272177

See all (1)

Prognosis

Further report of MEDS syndrome: Clinical and molecular delineation of a new Tunisian case.

Rjiba K, Soyah N, Kammoun M, Hadj Hmida I, Saad A, Mcelreavey K, Mougou-Zerelli S
Eur J Med Genet 2021 Sep;64(9):104285. Epub 2021 Jul 3 doi: 10.1016/j.ejmg.2021.104285. PMID: 34229114

A relatively common homozygous TRAPPC4 splicing variant is associated with an early-infantile neurodegenerative syndrome.

Ghosh SG, Scala M, Beetz C, Helman G, Stanley V, Yang X, Breuss MW, Mazaheri N, Selim L, Hadipour F, Pais L, Stutterd CA, Karageorgou V, Begtrup A, Crunk A, Juusola J, Willaert R, Flore LA, Kennelly K, Spencer C, Brown M, Trapane P, Hurst ACE, Lane Rutledge S, Goodloe DH, McDonald MT, Shashi V, Schoch K; Undiagnosed Diseases Network, Tomoum H, Zaitoun R, Hadipour Z, Galehdari H, Pagnamenta AT, Mojarrad M, Sedaghat A, Dias P, Quintas S, Eslahi A, Shariati G, Bauer P, Simons C, Houlden H, Issa MY, Zaki MS, Maroofian R, Gleeson JG
Eur J Hum Genet 2021 Feb;29(2):271-279. Epub 2020 Sep 8 doi: 10.1038/s41431-020-00717-5. PMID: 32901138 Free PMC Article

Neonatal hypoglycemia, early-onset diabetes and hypopituitarism due to the mutation in EIF2S3 gene causing MEHMO syndrome.

Stanik J, Skopkova M, Stanikova D, Brennerova K, Barak L, Ticha L, Hornova J, Klimes I, Gasperikova D
Physiol Res 2018 May 4;67(2):331-337. Epub 2018 Jan 5 doi: 10.33549/physiolres.933689. PMID: 29303605

Microcephaly, epilepsy, and neonatal diabetes due to compound heterozygous mutations in IER3IP1: insights into the natural history of a rare disorder.

Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors.

Poulton CJ, Schot R, Kia SK, Jones M, Verheijen FW, Venselaar H, de Wit MC, de Graaff E, Bertoli-Avella AM, Mancini GM
Am J Hum Genet 2011 Aug 12;89(2):265-76. doi: 10.1016/j.ajhg.2011.07.006. PMID: 21835305 Free PMC Article

See all (5)

Clinical prediction guides

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

Further report of MEDS syndrome: Clinical and molecular delineation of a new Tunisian case.

Rjiba K, Soyah N, Kammoun M, Hadj Hmida I, Saad A, Mcelreavey K, Mougou-Zerelli S
Eur J Med Genet 2021 Sep;64(9):104285. Epub 2021 Jul 3 doi: 10.1016/j.ejmg.2021.104285. PMID: 34229114

A relatively common homozygous TRAPPC4 splicing variant is associated with an early-infantile neurodegenerative syndrome.

A Recurrent De Novo Variant in NACC1 Causes a Syndrome Characterized by Infantile Epilepsy, Cataracts, and Profound Developmental Delay.

Schoch K, Meng L, Szelinger S, Bearden DR, Stray-Pedersen A, Busk OL, Stong N, Liston E, Cohn RD, Scaglia F, Rosenfeld JA, Tarpinian J, Skraban CM, Deardorff MA, Friedman JN, Akdemir ZC, Walley N, Mikati MA, Kranz PG, Jasien J, McConkie-Rosell A, McDonald M, Wechsler SB, Freemark M, Kansagra S, Freedman S, Bali D, Millan F, Bale S, Nelson SF, Lee H, Dorrani N; UCLA Clinical Genomics Center; Undiagnosed Diseases Network, Goldstein DB, Xiao R, Yang Y, Posey JE, Martinez-Agosto JA, Lupski JR, Wangler MF, Shashi V
Am J Hum Genet 2017 Feb 2;100(2):343-351. Epub 2017 Jan 26 doi: 10.1016/j.ajhg.2016.12.013. PMID: 28132692 Free PMC Article

Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors.

See all (5)

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Microcephaly, epilepsy, and diabetes syndrome 1(MEDS1)

Definition

Term Hierarchy

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Molecular resources

Consumer resources

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