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Cerebellar atrophy, developmental delay, and seizures(CADEDS)

MedGen UID:
1626119
Concept ID:
C4539985
Disease or Syndrome
Synonyms: CADEDS; CEREBELLAR ATROPHY, DEVELOPMENTAL DELAY, AND SEIZURES
 
Gene (location): KCNMA1 (10q22.3)
 
Monarch Initiative: MONDO:0060551
OMIM®: 617643

Clinical features

From HPO
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
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.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Bilateral tonic-clonic seizure with focal onset
MedGen UID:
164077
Concept ID:
C0877017
Disease or Syndrome
A bilateral tonic-clonic seizure with focal onset is a focal-onset seizure which progresses into a bilateral tonic-clonic phase.
Myoclonic seizure
MedGen UID:
1385980
Concept ID:
C4317123
Sign or Symptom
A myoclonic seizure is a type of motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).

Professional guidelines

PubMed

Ghasemi MR, Tehrani Fateh S, Moeinafshar A, Sadeghi H, Karimzadeh P, Mirfakhraie R, Rezaei M, Hashemi-Gorji F, Rezvani Kashani M, Fazeli Bavandpour F, Bagheri S, Moghimi P, Rostami M, Madannejad R, Roudgari H, Miryounesi M
BMC Med Genomics 2024 Feb 13;17(1):51. doi: 10.1186/s12920-024-01810-0. PMID: 38347586Free PMC Article
Muthaffar OY, Alqarni A, Shafei JA, Bahowarth SY, Alyazidi AS, Naseer MI
Genes Genomics 2024 Apr;46(4):475-487. Epub 2024 Jan 19 doi: 10.1007/s13258-023-01481-8. PMID: 38243045
Le Roux M, Barth M, Gueden S, Desbordes de Cepoy P, Aeby A, Vilain C, Hirsch E, de Saint Martin A, Portes VD, Lesca G, Riquet A, Chaton L, Villeneuve N, Villard L, Cances C, Valton L, Renaldo F, Vermersch AI, Altuzarra C, Nguyen-Morel MA, Van Gils J, Angelini C, Biraben A, Arnaud L, Riant F, Van Bogaert P
Eur J Paediatr Neurol 2021 Jul;33:75-85. Epub 2021 May 26 doi: 10.1016/j.ejpn.2021.05.010. PMID: 34102571

Recent clinical studies

Etiology

Sidpra J, Sudhakar S, Biswas A, Massey F, Turchetti V, Lau T, Cook E, Alvi JR, Elbendary HM, Jewell JL, Riva A, Orsini A, Vignoli A, Federico Z, Rosenblum J, Schoonjans AS, de Wachter M, Delgado Alvarez I, Felipe-Rucián A, Haridy NA, Haider S, Zaman M, Banu S, Anwaar N, Rahman F, Maqbool S, Yadav R, Salpietro V, Maroofian R, Patel R, Radhakrishnan R, Prabhu SP, Lichtenbelt K, Stewart H, Murakami Y, Löbel U, D'Arco F, Wakeling E, Jones W, Hay E, Bhate S, Jacques TS, Mirsky DM, Whitehead MT, Zaki MS, Sultan T, Striano P, Jansen AC, Lequin M, de Vries LS, Severino M, Edmondson AC, Menzies L, Campeau PM, Houlden H, McTague A, Efthymiou S, Mankad K
Brain 2024 Aug 1;147(8):2775-2790. doi: 10.1093/brain/awae056. PMID: 38456468Free PMC Article
Gur-Hartman T, Berkowitz O, Yosovich K, Roubertie A, Zanni G, Macaya A, Heimer G, Dueñas BP, Sival DA, Pode-Shakked B, López-Laso E, Humbertclaude V, Riant F, Bosco L, Cayron LB, Nissenkorn A, Nicita F, Bertini E, Hassin S, Ben Zeev B, Zerem A, Libzon S, Lev D, Linder I, Lerman-Sagie T, Blumkin L
Eur J Paediatr Neurol 2021 Jan;30:144-154. Epub 2020 Oct 20 doi: 10.1016/j.ejpn.2020.10.004. PMID: 33349592
Balestrini S, Mikati MA, Álvarez-García-Rovés R, Carboni M, Hunanyan AS, Kherallah B, McLean M, Prange L, De Grandis E, Gagliardi A, Pisciotta L, Stagnaro M, Veneselli E, Campistol J, Fons C, Pias-Peleteiro L, Brashear A, Miller C, Samões R, Brankovic V, Padiath QS, Potic A, Pilch J, Vezyroglou A, Bye AME, Davis AM, Ryan MM, Semsarian C, Hollingsworth G, Scheffer IE, Granata T, Nardocci N, Ragona F, Arzimanoglou A, Panagiotakaki E, Carrilho I, Zucca C, Novy J, Dzieżyc K, Parowicz M, Mazurkiewicz-Bełdzińska M, Weckhuysen S, Pons R, Groppa S, Sinden DS, Pitt GS, Tinker A, Ashworth M, Michalak Z, Thom M, Cross JH, Vavassori R, Kaski JP, Sisodiya SM
Neurology 2020 Nov 24;95(21):e2866-e2879. Epub 2020 Sep 10 doi: 10.1212/WNL.0000000000010794. PMID: 32913013Free PMC Article
Blackburn PR, Schultz MJ, Lahner CA, Li D, Bhoj E, Fisher LJ, Renaud DL, Kenney A, Ibrahim N, Hashem M, Zain Seidahmed M, Hasadsri L, Schrier Vergano SA, Alkuraya FS, Lanpher BC
Ann Clin Transl Neurol 2020 Jun;7(6):1013-1028. Epub 2020 Jun 9 doi: 10.1002/acn3.51074. PMID: 32519519Free PMC Article
Claerhout H, Witters P, Régal L, Jansen K, Van Hoestenberghe MR, Breckpot J, Vermeersch P
J Inherit Metab Dis 2018 Jan;41(1):101-108. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0089-4. PMID: 28980090

Diagnosis

Alvarez C, Grimmel M, Ebrahimi-Fakhari D, Paul VG, Deininger N, Riess A, Haack T, Gardella E, Møller RS, Bayat A
Clin Genet 2023 May;103(5):566-573. Epub 2023 Jan 11 doi: 10.1111/cge.14275. PMID: 36453471
Giacomini T, Nuovo S, Zanni G, Mancardi MM, Cusmai R, Pepi C, Bertini E, Valente EM, Battini R, Ferrari A, Romaniello R, Zucca C, Borgatti R, Uccella S, Severino M, Striano P, Pistorio A, Prato G, De Grandis E, Nobili L, Pisciotta L
Eur J Paediatr Neurol 2021 Mar;31:61-69. Epub 2021 Feb 19 doi: 10.1016/j.ejpn.2021.02.006. PMID: 33640666
Kunii M, Doi H, Hashiguchi S, Matsuishi T, Sakai Y, Iai M, Okubo M, Nakamura H, Takahashi K, Katsumoto A, Tada M, Takeuchi H, Ishikawa T, Miyake N, Saitsu H, Matsumoto N, Tanaka F
J Neurol Sci 2020 Sep 15;416:117047. Epub 2020 Jul 17 doi: 10.1016/j.jns.2020.117047. PMID: 32736238
Claerhout H, Witters P, Régal L, Jansen K, Van Hoestenberghe MR, Breckpot J, Vermeersch P
J Inherit Metab Dis 2018 Jan;41(1):101-108. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0089-4. PMID: 28980090
Tabarki B, AlMajhad N, AlHashem A, Shaheen R, Alkuraya FS
Hum Genet 2016 Nov;135(11):1295-1298. Epub 2016 Aug 27 doi: 10.1007/s00439-016-1726-y. PMID: 27567911

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
García Segarra N, Gautschi I, Mittaz-Crettol L, Kallay Zetchi C, Al-Qusairi L, Van Bemmelen MX, Maeder P, Bonafé L, Schild L, Roulet-Perez E
J Neurol Sci 2014 Jul 15;342(1-2):69-78. Epub 2014 Apr 27 doi: 10.1016/j.jns.2014.04.027. PMID: 24836863
Lamperti C, Naini A, Hirano M, De Vivo DC, Bertini E, Servidei S, Valeriani M, Lynch D, Banwell B, Berg M, Dubrovsky T, Chiriboga C, Angelini C, Pegoraro E, DiMauro S
Neurology 2003 Apr 8;60(7):1206-8. doi: 10.1212/01.wnl.0000055089.39373.fc. PMID: 12682339
Al-Essa MA, Bakheet SM, Patay ZJ, Powe JE, Ozand PT
Brain Dev 2000 Mar;22(2):127-31. doi: 10.1016/s0387-7604(99)00121-7. PMID: 10722966
Vossler DG, Lee JK, Ko TS
J Child Neurol 1999 May;14(5):282-8. doi: 10.1177/088307389901400503. PMID: 10342594

Prognosis

Sidpra J, Sudhakar S, Biswas A, Massey F, Turchetti V, Lau T, Cook E, Alvi JR, Elbendary HM, Jewell JL, Riva A, Orsini A, Vignoli A, Federico Z, Rosenblum J, Schoonjans AS, de Wachter M, Delgado Alvarez I, Felipe-Rucián A, Haridy NA, Haider S, Zaman M, Banu S, Anwaar N, Rahman F, Maqbool S, Yadav R, Salpietro V, Maroofian R, Patel R, Radhakrishnan R, Prabhu SP, Lichtenbelt K, Stewart H, Murakami Y, Löbel U, D'Arco F, Wakeling E, Jones W, Hay E, Bhate S, Jacques TS, Mirsky DM, Whitehead MT, Zaki MS, Sultan T, Striano P, Jansen AC, Lequin M, de Vries LS, Severino M, Edmondson AC, Menzies L, Campeau PM, Houlden H, McTague A, Efthymiou S, Mankad K
Brain 2024 Aug 1;147(8):2775-2790. doi: 10.1093/brain/awae056. PMID: 38456468Free PMC Article
Pavone P, Pappalardo XG, Ruggieri M, Falsaperla R, Parano E
Medicine (Baltimore) 2022 Aug 5;101(31):e29413. doi: 10.1097/MD.0000000000029413. PMID: 35945798Free PMC Article
Giacomini T, Nuovo S, Zanni G, Mancardi MM, Cusmai R, Pepi C, Bertini E, Valente EM, Battini R, Ferrari A, Romaniello R, Zucca C, Borgatti R, Uccella S, Severino M, Striano P, Pistorio A, Prato G, De Grandis E, Nobili L, Pisciotta L
Eur J Paediatr Neurol 2021 Mar;31:61-69. Epub 2021 Feb 19 doi: 10.1016/j.ejpn.2021.02.006. PMID: 33640666
Claerhout H, Witters P, Régal L, Jansen K, Van Hoestenberghe MR, Breckpot J, Vermeersch P
J Inherit Metab Dis 2018 Jan;41(1):101-108. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0089-4. PMID: 28980090
Freeze HH, Eklund EA, Ng BG, Patterson MC
Lancet Neurol 2012 May;11(5):453-66. doi: 10.1016/S1474-4422(12)70040-6. PMID: 22516080Free PMC Article

Clinical prediction guides

Sidpra J, Sudhakar S, Biswas A, Massey F, Turchetti V, Lau T, Cook E, Alvi JR, Elbendary HM, Jewell JL, Riva A, Orsini A, Vignoli A, Federico Z, Rosenblum J, Schoonjans AS, de Wachter M, Delgado Alvarez I, Felipe-Rucián A, Haridy NA, Haider S, Zaman M, Banu S, Anwaar N, Rahman F, Maqbool S, Yadav R, Salpietro V, Maroofian R, Patel R, Radhakrishnan R, Prabhu SP, Lichtenbelt K, Stewart H, Murakami Y, Löbel U, D'Arco F, Wakeling E, Jones W, Hay E, Bhate S, Jacques TS, Mirsky DM, Whitehead MT, Zaki MS, Sultan T, Striano P, Jansen AC, Lequin M, de Vries LS, Severino M, Edmondson AC, Menzies L, Campeau PM, Houlden H, McTague A, Efthymiou S, Mankad K
Brain 2024 Aug 1;147(8):2775-2790. doi: 10.1093/brain/awae056. PMID: 38456468Free PMC Article
Phulpagar P, Holla VV, Tomar D, Kamble N, Yadav R, Pal PK, Muthusamy B
J Hum Genet 2023 Dec;68(12):859-866. Epub 2023 Sep 26 doi: 10.1038/s10038-023-01195-5. PMID: 37752213
Gur-Hartman T, Berkowitz O, Yosovich K, Roubertie A, Zanni G, Macaya A, Heimer G, Dueñas BP, Sival DA, Pode-Shakked B, López-Laso E, Humbertclaude V, Riant F, Bosco L, Cayron LB, Nissenkorn A, Nicita F, Bertini E, Hassin S, Ben Zeev B, Zerem A, Libzon S, Lev D, Linder I, Lerman-Sagie T, Blumkin L
Eur J Paediatr Neurol 2021 Jan;30:144-154. Epub 2020 Oct 20 doi: 10.1016/j.ejpn.2020.10.004. PMID: 33349592
Wang J, Rousseau J, Kim E, Ehresmann S, Cheng YT, Duraine L, Zuo Z, Park YJ, Li-Kroeger D, Bi W, Wong LJ, Rosenfeld J, Gleeson J, Faqeih E, Alkuraya FS, Wierenga KJ, Chen J, Afenjar A, Nava C, Doummar D, Keren B, Juusola J, Grompe M, Bellen HJ, Campeau PM
Am J Hum Genet 2019 Dec 5;105(6):1237-1253. Epub 2019 Nov 27 doi: 10.1016/j.ajhg.2019.11.002. PMID: 31785787Free PMC Article
Claerhout H, Witters P, Régal L, Jansen K, Van Hoestenberghe MR, Breckpot J, Vermeersch P
J Inherit Metab Dis 2018 Jan;41(1):101-108. Epub 2017 Oct 4 doi: 10.1007/s10545-017-0089-4. PMID: 28980090

Recent systematic reviews

Stoian A, Bajko Z, Bălașa R, Andone S, Stoian M, Ormenișan I, Muntean C, Bănescu C
Biomolecules 2024 Feb 23;14(3) doi: 10.3390/biom14030270. PMID: 38540691Free PMC Article

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