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Neurodevelopmental disorder with microcephaly, ataxia, and seizures(NEDMAS)

MedGen UID:
1613354
Concept ID:
C4540188
Disease or Syndrome
Synonyms: NEDMAS; NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, ATAXIA, AND SEIZURES
 
Gene (location): SARS1 (1p13.3)
 
Monarch Initiative: MONDO:0060577
OMIM®: 617709

Definition

Neurodevelopmental disorder with microcephaly, ataxia, and seizures (NEDMAS) is an autosomal recessive disorder characterized by global developmental delay and early-onset seizures. More variable features may include deafness, cardiomyopathy, and severe febrile decompensations (summary by Ravel et al., 2021). [from OMIM]

Clinical features

From HPO
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Slender build
MedGen UID:
376828
Concept ID:
C1850573
Finding
Asthenic habitus refers to a slender build with long limbs, an angular profile, and prominent muscles or bones.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Intellectual disability, moderate
MedGen UID:
7680
Concept ID:
C0026351
Mental or Behavioral Dysfunction
Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.
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.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.

Professional guidelines

PubMed

Engel C, Valence S, Delplancq G, Maroofian R, Accogli A, Agolini E, Alkuraya FS, Baglioni V, Bagnasco I, Becmeur-Lefebvre M, Bertini E, Borggraefe I, Brischoux-Boucher E, Bruel AL, Brusco A, Bubshait DK, Cabrol C, Cilio MR, Cornet MC, Coubes C, Danhaive O, Delague V, Denommé-Pichon AS, Di Giacomo MC, Doco-Fenzy M, Engels H, Cremer K, Gérard M, Gleeson JG, Heron D, Goffeney J, Guimier A, Harms FL, Houlden H, Iacomino M, Kaiyrzhanov R, Kamien B, Karimiani EG, Kraus D, Kuentz P, Kutsche K, Lederer D, Massingham L, Mignot C, Morris-Rosendahl D, Nagarajan L, Odent S, Ormières C, Partlow JN, Pasquier L, Penney L, Philippe C, Piccolo G, Poulton C, Putoux A, Rio M, Rougeot C, Salpietro V, Scheffer I, Schneider A, Srivastava S, Straussberg R, Striano P, Valente EM, Venot P, Villard L, Vitobello A, Wagner J, Wagner M, Zaki MS, Zara F, Lesca G, Yassaee VR, Miryounesi M, Hashemi-Gorji F, Beiraghi M, Ashrafzadeh F, Galehdari H, Walsh C, Novelli A, Tacke M, Sadykova D, Maidyrov Y, Koneev K, Shashkin C, Capra V, Zamani M, Van Maldergem L, Burglen L, Piard J
Eur J Hum Genet 2023 Sep;31(9):1023-1031. Epub 2023 Jun 21 doi: 10.1038/s41431-023-01410-z. PMID: 37344571Free PMC Article

Recent clinical studies

Etiology

Engel C, Valence S, Delplancq G, Maroofian R, Accogli A, Agolini E, Alkuraya FS, Baglioni V, Bagnasco I, Becmeur-Lefebvre M, Bertini E, Borggraefe I, Brischoux-Boucher E, Bruel AL, Brusco A, Bubshait DK, Cabrol C, Cilio MR, Cornet MC, Coubes C, Danhaive O, Delague V, Denommé-Pichon AS, Di Giacomo MC, Doco-Fenzy M, Engels H, Cremer K, Gérard M, Gleeson JG, Heron D, Goffeney J, Guimier A, Harms FL, Houlden H, Iacomino M, Kaiyrzhanov R, Kamien B, Karimiani EG, Kraus D, Kuentz P, Kutsche K, Lederer D, Massingham L, Mignot C, Morris-Rosendahl D, Nagarajan L, Odent S, Ormières C, Partlow JN, Pasquier L, Penney L, Philippe C, Piccolo G, Poulton C, Putoux A, Rio M, Rougeot C, Salpietro V, Scheffer I, Schneider A, Srivastava S, Straussberg R, Striano P, Valente EM, Venot P, Villard L, Vitobello A, Wagner J, Wagner M, Zaki MS, Zara F, Lesca G, Yassaee VR, Miryounesi M, Hashemi-Gorji F, Beiraghi M, Ashrafzadeh F, Galehdari H, Walsh C, Novelli A, Tacke M, Sadykova D, Maidyrov Y, Koneev K, Shashkin C, Capra V, Zamani M, Van Maldergem L, Burglen L, Piard J
Eur J Hum Genet 2023 Sep;31(9):1023-1031. Epub 2023 Jun 21 doi: 10.1038/s41431-023-01410-z. PMID: 37344571Free PMC Article
Manivannan SN, Roovers J, Smal N, Myers CT, Turkdogan D, Roelens F, Kanca O, Chung HL, Scholz T, Hermann K, Bierhals T, Caglayan HS, Stamberger H; MAE Working Group of EuroEPINOMICS RES Consortium, Mefford H, de Jonghe P, Yamamoto S, Weckhuysen S, Bellen HJ
Brain 2022 Jun 3;145(5):1684-1697. doi: 10.1093/brain/awab409. PMID: 34788397Free PMC Article
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: 32738225Free PMC Article
Hanzlik E, Klinger SA, Carson R, Duis J
J Clin Sleep Med 2020 Apr 15;16(4):591-595. doi: 10.5664/jcsm.8284. PMID: 32022663Free PMC Article
Jiang B, Glover JN, Weinfeld M
Mech Ageing Dev 2017 Jan;161(Pt A):130-140. Epub 2016 Jul 25 doi: 10.1016/j.mad.2016.07.009. PMID: 27470939Free PMC Article

Diagnosis

Karaer K, Karaer D, Yüksel Z, Işikay S
Clin Dysmorphol 2022 Oct 1;31(4):167-173. Epub 2022 Jul 14 doi: 10.1097/MCD.0000000000000426. PMID: 36004946
Manivannan SN, Roovers J, Smal N, Myers CT, Turkdogan D, Roelens F, Kanca O, Chung HL, Scholz T, Hermann K, Bierhals T, Caglayan HS, Stamberger H; MAE Working Group of EuroEPINOMICS RES Consortium, Mefford H, de Jonghe P, Yamamoto S, Weckhuysen S, Bellen HJ
Brain 2022 Jun 3;145(5):1684-1697. doi: 10.1093/brain/awab409. PMID: 34788397Free PMC Article
Ji J, Shen L, Bootwalla M, Quindipan C, Tatarinova T, Maglinte DT, Buckley J, Raca G, Saitta SC, Biegel JA, Gai X
Cold Spring Harb Mol Case Stud 2019 Apr;5(2) Epub 2019 Apr 1 doi: 10.1101/mcs.a003756. PMID: 30755392Free PMC Article
Sachdeva R, Donkers SJ, Kim SY
Clin Anat 2016 Jul;29(5):561-7. Epub 2015 Nov 17 doi: 10.1002/ca.22659. PMID: 26480021
Verrotti A, D'Egidio C, Agostinelli S, Gobbi G
Eur J Paediatr Neurol 2012 Jan;16(1):3-9. Epub 2011 Oct 1 doi: 10.1016/j.ejpn.2011.09.005. PMID: 21962875

Therapy

Muthusamy K, Perez-Ortiz JM, Ligezka AN, Altassan R, Johnsen C, Schultz MJ, Patterson MC, Morava E
Genet Med 2024 Feb;26(2):101027. Epub 2023 Nov 10 doi: 10.1016/j.gim.2023.101027. PMID: 37955240
Copping NA, McTighe SM, Fink KD, Silverman JL
Neurotherapeutics 2021 Jul;18(3):1535-1547. Epub 2021 Sep 15 doi: 10.1007/s13311-021-01082-x. PMID: 34528170Free PMC Article
Coorg R, Weisenberg JL
Pediatr Neurol 2015 Dec;53(6):527-31. Epub 2015 Jul 22 doi: 10.1016/j.pediatrneurol.2015.07.007. PMID: 26421989
Friedman JR, Thiele EA, Wang D, Levine KB, Cloherty EK, Pfeifer HH, De Vivo DC, Carruthers A, Natowicz MR
Mov Disord 2006 Feb;21(2):241-5. doi: 10.1002/mds.20660. PMID: 16149086
Overweg-Plandsoen WC, Groener JE, Wang D, Onkenhout W, Brouwer OF, Bakker HD, De Vivo DC
J Inherit Metab Dis 2003;26(6):559-63. doi: 10.1023/a:1025999914822. PMID: 14605501

Prognosis

Muthusamy K, Perez-Ortiz JM, Ligezka AN, Altassan R, Johnsen C, Schultz MJ, Patterson MC, Morava E
Genet Med 2024 Feb;26(2):101027. Epub 2023 Nov 10 doi: 10.1016/j.gim.2023.101027. PMID: 37955240
Himes RW, Chiou EH, Queliza K, Shouval DS, Somech R, Agarwal S, Jajoo K, Ziegler DS, Kratz CP, Huang J, Lucas TL, Myers KC, Nelson AS, DiNardo CD, Alter BP, Giri N, Khincha PP, McReynolds LJ, Dufour C, Pierri F, Goldman FD, Sherif Y, Savage SA, Miloh T, Bertuch AA
J Pediatr 2021 Mar;230:55-61.e4. Epub 2020 Sep 21 doi: 10.1016/j.jpeds.2020.09.038. PMID: 32971146
Oatts JT, Duncan JL, Hoyt CS, Slavotinek AM, Moore AT
Ophthalmic Genet 2017 Dec;38(6):559-561. Epub 2017 Mar 2 doi: 10.1080/13816810.2017.1290118. PMID: 28635423
Sachdeva R, Donkers SJ, Kim SY
Clin Anat 2016 Jul;29(5):561-7. Epub 2015 Nov 17 doi: 10.1002/ca.22659. PMID: 26480021
Sofou K, Moslemi AR, Kollberg G, Bjarnadóttir I, Oldfors A, Nennesmo I, Holme E, Tulinius M, Darin N
Eur J Paediatr Neurol 2012 Jul;16(4):379-89. Epub 2012 Jan 10 doi: 10.1016/j.ejpn.2011.12.006. PMID: 22237560

Clinical prediction guides

Maroofian R, Zamani M, Kaiyrzhanov R, Liebmann L, Karimiani EG, Vona B, Huebner AK, Calame DG, Misra VK, Sadeghian S, Azizimalamiri R, Mohammadi MH, Zeighami J, Heydaran S, Toosi MB, Akhondian J, Babaei M, Hashemi N, Schnur RE, Suri M, Setzke J, Wagner M, Brunet T, Grochowski CM, Emrick L, Chung WK, Hellmich UA, Schmidts M, Lupski JR, Galehdari H, Severino M, Houlden H, Hübner CA
Genet Med 2024 Mar;26(3):101034. Epub 2023 Dec 3 doi: 10.1016/j.gim.2023.101034. PMID: 38054405
Muthusamy K, Perez-Ortiz JM, Ligezka AN, Altassan R, Johnsen C, Schultz MJ, Patterson MC, Morava E
Genet Med 2024 Feb;26(2):101027. Epub 2023 Nov 10 doi: 10.1016/j.gim.2023.101027. PMID: 37955240
Kaiyrzhanov R, Rad A, Lin SJ, Bertoli-Avella A, Kallemeijn WW, Godwin A, Zaki MS, Huang K, Lau T, Petree C, Efthymiou S, Karimiani EG, Hempel M, Normand EA, Rudnik-Schöneborn S, Schatz UA, Baggelaar MP, Ilyas M, Sultan T, Alvi JR, Ganieva M, Fowler B, Aanicai R, Tayfun GA, Al Saman A, Alswaid A, Amiri N, Asilova N, Shotelersuk V, Yeetong P, Azam M, Babaei M, Monajemi GB, Mohammadi P, Samie S, Banu SH, Pinto Basto J, Kortüm F, Bauer M, Bauer P, Beetz C, Garshasbi M, Issa AH, Eyaid W, Ahmed H, Hashemi N, Hassanpour K, Herman I, Ibrohimov S, Abdul-Majeed BA, Imdad M, Isrofilov M, Kaiyal Q, Khan S, Kirmse B, Koster J, Lourenço CM, Mitani T, Moldovan O, Murphy D, Najafi M, Pehlivan D, Rocha ME, Salpietro V, Schmidts M, Shalata A, Mahroum M, Talbeya JK, Taylor RW, Vazquez D, Vetro A, Waterham HR, Zaman M, Schrader TA, Chung WK, Guerrini R, Lupski JR, Gleeson J, Suri M, Jamshidi Y, Bhatia KP, Vona B, Schrader M, Severino M, Guille M, Tate EW, Varshney GK, Houlden H, Maroofian R
Brain 2024 Apr 4;147(4):1436-1456. doi: 10.1093/brain/awad380. PMID: 37951597Free PMC Article
Mathieu ML, de Bellescize J, Till M, Flurin V, Labalme A, Chatron N, Sanlaville D, Chemaly N, des Portes V, Ostrowsky K, Arzimanoglou A, Lesca G
Eur J Paediatr Neurol 2018 Nov;22(6):1124-1132. Epub 2018 Jul 21 doi: 10.1016/j.ejpn.2018.07.004. PMID: 30126759
Hergüner MO, Incecik F, Altunbaşak S, Kiriş N
Pediatr Neurol 2008 Jun;38(6):411-4. doi: 10.1016/j.pediatrneurol.2008.02.007. PMID: 18486823

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