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Late-infantile neuronal ceroid lipofuscinosis

MedGen UID:
9589
Concept ID:
C0022340
Disease or Syndrome
Synonym: Jansky-Bielschowsky disease
SNOMED CT: Late-infantile neuronal ceroid lipofuscinosis (14637005); Bielschowsky-Jansky disease (14637005); Amaurotic idiocy, early juvenile type (14637005); Amaurotic idiocy, late infantile type (14637005); Dollinger-Bielschowsky syndrome (14637005); Dollinger-Bielschowsky type neuronal ceroid lipofuscinosis (14637005); Bielschowsky-Jansky type neuronal ceroid lipofuscinosis (14637005); Amaurotic idiocy early juvenile type (14637005); Amaurotic idiocy late infantile type (14637005); Late infantile neuronal ceroid lipofuscinosis (14637005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Monarch Initiative: MONDO:0015674
Orphanet: ORPHA168491

Definition

CLN2 disease is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition typically begin between ages 2 and 4. The initial features usually include recurrent seizures (epilepsy) and difficulty coordinating movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision loss. CLN2 disease affects motor skills, such as sitting and walking, and speech development. This condition also causes the loss of previously acquired skills (developmental regression), intellectual disability that gradually gets worse, and behavioral problems. Individuals with this condition often require the use of a wheelchair by late childhood and typically do not survive past their teens.

Some children with CLN2 disease do not develop symptoms until later in childhood, typically after age 4. These individuals tend to have milder features overall compared to those diagnosed earlier, but with more severe ataxia. They have a shortened life expectancy, although they tend to survive into adulthood.

CLN2 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. [from MedlinePlus Genetics]

Professional guidelines

PubMed

Gutić M, Milosavljević MN, Safiye T, Milidrag A, Jankovic SM
Expert Rev Pharmacoecon Outcomes Res 2023 Jun;23(5):561-570. Epub 2023 Apr 3 doi: 10.1080/14737167.2023.2197213. PMID: 36994735
Leal-Pardinas F, Truty R, McKnight DA, Johnson B, Morales A, Bristow SL, Yar Pang T, Cohen-Pfeffer J, Izzo E, Sankar R, Koh S, Wirrell EC, Millichap JJ, Aradhya S
Epilepsia 2022 Jul;63(7):e68-e73. Epub 2022 May 10 doi: 10.1111/epi.17269. PMID: 35474188Free PMC Article
Williams RE, Adams HR, Blohm M, Cohen-Pfeffer JL, de Los Reyes E, Denecke J, Drago K, Fairhurst C, Frazier M, Guelbert N, Kiss S, Kofler A, Lawson JA, Lehwald L, Leung MA, Mikhaylova S, Mink JW, Nickel M, Shediac R, Sims K, Specchio N, Topcu M, von Löbbecke I, West A, Zernikow B, Schulz A
Pediatr Neurol 2017 Apr;69:102-112. Epub 2017 Feb 4 doi: 10.1016/j.pediatrneurol.2017.01.034. PMID: 28335910

Recent clinical studies

Etiology

Schaefers J, van der Giessen LJ, Klees C, Jacobs EH, Sieverdink S, Dremmen MHG, Spoor JKH, van der Ploeg AT, van den Hout JMP, Huidekoper HH
Orphanet J Rare Dis 2021 May 14;16(1):221. doi: 10.1186/s13023-021-01858-6. PMID: 33990214Free PMC Article
Johnson AM, Mandelstam S, Andrews I, Boysen K, Yaplito-Lee J, Fietz M, Nagarajan L, Rodriguez-Casero V, Ryan MM, Smith N, Scheffer IE, Ellaway C
J Paediatr Child Health 2020 Aug;56(8):1210-1218. Epub 2020 Apr 24 doi: 10.1111/jpc.14890. PMID: 32329550Free PMC Article
Beltrán L, Valenzuela GR, Loos M, Vargas R, Lizama R, Spinsanti P, Caraballo R
Epilepsy Res 2018 Aug;144:49-52. Epub 2018 May 16 doi: 10.1016/j.eplepsyres.2018.05.005. PMID: 29778029
Kim K, Kleinman HK, Lee HJ, Pahan K
Orphanet J Rare Dis 2017 Jun 17;12(1):113. doi: 10.1186/s13023-017-0663-8. PMID: 28623936Free PMC Article
Goebel HH
J Child Neurol 1995 Nov;10(6):424-37. doi: 10.1177/088307389501000602. PMID: 8576551

Diagnosis

O'Neal M, Noher de Halac I, Aylward SC, Yildiz V, Zapanta B, Abreu N, de Los Reyes E
Pediatr Neurol 2024 May;154:51-57. Epub 2024 Mar 1 doi: 10.1016/j.pediatrneurol.2024.02.010. PMID: 38531163
Thompson DA, Handley SE, Henderson RH, Marmoy OR, Gissen P
Eye (Lond) 2021 Sep;35(9):2438-2448. Epub 2021 Jul 16 doi: 10.1038/s41433-021-01594-y. PMID: 34272513Free PMC Article
Johnson AM, Mandelstam S, Andrews I, Boysen K, Yaplito-Lee J, Fietz M, Nagarajan L, Rodriguez-Casero V, Ryan MM, Smith N, Scheffer IE, Ellaway C
J Paediatr Child Health 2020 Aug;56(8):1210-1218. Epub 2020 Apr 24 doi: 10.1111/jpc.14890. PMID: 32329550Free PMC Article
Beltrán L, Valenzuela GR, Loos M, Vargas R, Lizama R, Spinsanti P, Caraballo R
Epilepsy Res 2018 Aug;144:49-52. Epub 2018 May 16 doi: 10.1016/j.eplepsyres.2018.05.005. PMID: 29778029
Goebel HH
J Child Neurol 1995 Nov;10(6):424-37. doi: 10.1177/088307389501000602. PMID: 8576551

Therapy

Gutić M, Milosavljević MN, Safiye T, Milidrag A, Jankovic SM
Expert Rev Pharmacoecon Outcomes Res 2023 Jun;23(5):561-570. Epub 2023 Apr 3 doi: 10.1080/14737167.2023.2197213. PMID: 36994735
Lewis G, Morrill AM, Conway-Allen SL, Kim B
J Child Neurol 2020 Apr;35(5):348-353. Epub 2019 Dec 29 doi: 10.1177/0883073819895694. PMID: 31884868
Kim K, Kleinman HK, Lee HJ, Pahan K
Orphanet J Rare Dis 2017 Jun 17;12(1):113. doi: 10.1186/s13023-017-0663-8. PMID: 28623936Free PMC Article
Kohlschütter A, Schulz A
Pediatr Endocrinol Rev 2016 Jun;13 Suppl 1:682-8. PMID: 27491216
Souweidane MM, Fraser JF, Arkin LM, Sondhi D, Hackett NR, Kaminsky SM, Heier L, Kosofsky BE, Worgall S, Crystal RG, Kaplitt MG
J Neurosurg Pediatr 2010 Aug;6(2):115-22. doi: 10.3171/2010.4.PEDS09507. PMID: 20672930Free PMC Article

Prognosis

Mandel H, Cohen Katsanelson K, Khayat M, Chervinsky I, Vladovski E, Iancu TC, Indelman M, Horovitz Y, Sprecher E, Shalev SA, Spiegel R
Eur J Med Genet 2014 Nov-Dec;57(11-12):607-12. Epub 2014 Sep 28 doi: 10.1016/j.ejmg.2014.09.004. PMID: 25270050
Pérez-Poyato MS, Marfa MP, Abizanda IF, Rodriguez-Revenga L, Sánchez VC, González MJ, Puñal JE, Pérez AV, González MM, Bermejo AM, Hernández EM, Rosell MJ, Gort L, Milá M
J Child Neurol 2013 Apr;28(4):470-8. Epub 2012 Jul 25 doi: 10.1177/0883073812448459. PMID: 22832778
Kamate M, Prashanth GP, Hattiholi V
Neurol India 2012 May-Jun;60(3):316-20. doi: 10.4103/0028-3886.98524. PMID: 22824694
Wiśniewski KE, Zhong N, Kida E, Kaczmarski W, Kaczmarski A, Connell F, Brooks SS, Brown WT
Folia Neuropathol 1997;35(2):73-9. PMID: 9377079
Sharp J, Savukoski M, Wheeler RB, Harris J, Järvelä I, Peltonen L, Gardiner M, Williams R
Am J Med Genet 1995 Jun 5;57(2):348-9. doi: 10.1002/ajmg.1320570249. PMID: 7668361

Clinical prediction guides

O'Neal M, Noher de Halac I, Aylward SC, Yildiz V, Zapanta B, Abreu N, de Los Reyes E
Pediatr Neurol 2024 May;154:51-57. Epub 2024 Mar 1 doi: 10.1016/j.pediatrneurol.2024.02.010. PMID: 38531163
Dulz S, Schwering C, Wildner J, Spartalis C, Schuettauf F, Bartsch U, Wibbeler E, Nickel M, Spitzer MS, Atiskova Y, Schulz A
Br J Ophthalmol 2023 Oct;107(10):1478-1483. Epub 2022 Jun 30 doi: 10.1136/bjo-2022-321260. PMID: 35772852
Schaefers J, van der Giessen LJ, Klees C, Jacobs EH, Sieverdink S, Dremmen MHG, Spoor JKH, van der Ploeg AT, van den Hout JMP, Huidekoper HH
Orphanet J Rare Dis 2021 May 14;16(1):221. doi: 10.1186/s13023-021-01858-6. PMID: 33990214Free PMC Article
Gavin M, Khatoon S, Marchi EJ, Mevs CA, Bolton DC, Velinov MT, Junaid MA
Clin Chim Acta 2020 Aug;507:62-68. Epub 2020 Apr 13 doi: 10.1016/j.cca.2020.04.010. PMID: 32298681
Vesa J, Peltonen L
Curr Mol Med 2002 Aug;2(5):439-44. doi: 10.2174/1566524023362311. PMID: 12125809

Recent systematic reviews

Chen ZR, Liu DT, Meng H, Liu L, Bian WJ, Liu XR, Zhu WW, He Y, Wang J, Tang B, Su T, Yi YH
Seizure 2019 Jul;69:180-185. Epub 2018 Sep 2 doi: 10.1016/j.seizure.2018.08.027. PMID: 31059981

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