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Neuronal ceroid lipofuscinosis

MedGen UID:
10326
Concept ID:
C0027877
Disease or Syndrome
Synonym: Ceroid storage disease
SNOMED CT: Neuronal ceroid lipofuscinosis (42012007); Cerebromacular degeneration (42012007); Cerebromacular dystrophy (42012007); Pigmentary retinal lipoid neuronal heredodegeneration (42012007)
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).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Related genes: MFSD8, DNAJC5, CLN6, PPT1, CLN8, CTSD, CLN5, CLN3, TPP1
 
Monarch Initiative: MONDO:0016295
OMIM® Phenotypic series: PS256730
Orphanet: ORPHA216

Definition

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.

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 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. [from MedlinePlus Genetics]

Term Hierarchy

Follow this link to review classifications for Neuronal ceroid lipofuscinosis in Orphanet.

Professional guidelines

PubMed

Simon MJ, Logan T, DeVos SL, Di Paolo G
Trends Cell Biol 2023 Apr;33(4):324-339. Epub 2022 Oct 13 doi: 10.1016/j.tcb.2022.09.006. PMID: 36244875
Kohlschütter A, Schulz A, Bartsch U, Storch S
CNS Drugs 2019 Apr;33(4):315-325. doi: 10.1007/s40263-019-00620-8. PMID: 30877620Free PMC Article
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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

Saleh MM, Hamhom AM, Al-Otaibi A, AlGhamdi M, Housawi Y, Aljadhai YI, Alameer S, Almannai M, Jad LA, Alwadei AH, Tabassum S, Alsaman A, AlAsmari A, Al Mutairi F, Althiyab H, Bashiri FA, AlHumaidi S, Alfadhel M, Mink JW, AlHashim A, Faqeih EA; Saudi NCL Study Consortium
Pediatr Neurol 2024 Jun;155:149-155. Epub 2024 Mar 7 doi: 10.1016/j.pediatrneurol.2024.03.004. PMID: 38653183
Rhinn H, Tatton N, McCaughey S, Kurnellas M, Rosenthal A
Trends Pharmacol Sci 2022 Aug;43(8):641-652. Epub 2022 Jan 15 doi: 10.1016/j.tips.2021.11.015. PMID: 35039149
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Goebel HH
J Child Neurol 1995 Nov;10(6):424-37. doi: 10.1177/088307389501000602. PMID: 8576551

Diagnosis

Specchio N, Ferretti A, Trivisano M, Pietrafusa N, Pepi C, Calabrese C, Livadiotti S, Simonetti A, Rossi P, Curatolo P, Vigevano F
Drugs 2021 Jan;81(1):101-123. doi: 10.1007/s40265-020-01440-7. PMID: 33242182
Gundersen CB
Prog Neurobiol 2020 May;188:101758. Epub 2020 Feb 7 doi: 10.1016/j.pneurobio.2020.101758. PMID: 32044380
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Mole SE, Anderson G, Band HA, Berkovic SF, Cooper JD, Kleine Holthaus SM, McKay TR, Medina DL, Rahim AA, Schulz A, Smith AJ
Lancet Neurol 2019 Jan;18(1):107-116. Epub 2018 Nov 21 doi: 10.1016/S1474-4422(18)30368-5. PMID: 30470609
Goebel HH
J Child Neurol 1995 Nov;10(6):424-37. doi: 10.1177/088307389501000602. PMID: 8576551

Therapy

Naseri N, Sharma M, Velinov M
Clin Genet 2021 Jan;99(1):111-118. Epub 2020 Aug 26 doi: 10.1111/cge.13829. PMID: 32783189Free PMC Article
Mirza M, Vainshtein A, DiRonza A, Chandrachud U, Haslett LJ, Palmieri M, Storch S, Groh J, Dobzinski N, Napolitano G, Schmidtke C, Kerkovich DM
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Kohlschütter A, Schulz A, Bartsch U, Storch S
CNS Drugs 2019 Apr;33(4):315-325. doi: 10.1007/s40263-019-00620-8. PMID: 30877620Free PMC Article
Markham A
Drugs 2017 Jul;77(11):1247-1249. doi: 10.1007/s40265-017-0771-8. PMID: 28589525
Kohlschütter A, Schulz A
Pediatr Endocrinol Rev 2016 Jun;13 Suppl 1:682-8. PMID: 27491216

Prognosis

Galosi S, Edani BH, Martinelli S, Hansikova H, Eklund EA, Caputi C, Masuelli L, Corsten-Janssen N, Srour M, Oegema R, Bosch DGM, Ellis CA, Amlie-Wolf L, Accogli A, Atallah I, Averdunk L, Barañano KW, Bei R, Bagnasco I, Brusco A, Demarest S, Alaix AS, Di Bonaventura C, Distelmaier F, Elmslie F, Gan-Or Z, Good JM, Gripp K, Kamsteeg EJ, Macnamara E, Marcelis C, Mercier N, Peeden J, Pizzi S, Pannone L, Shinawi M, Toro C, Verbeek NE, Venkateswaran S, Wheeler PG, Zdrazilova L, Zhang R, Zorzi G, Guerrini R, Sessa WC, Lefeber DJ, Tartaglia M, Hamdan FF, Grabińska KA, Leuzzi V
Brain 2022 Mar 29;145(1):208-223. doi: 10.1093/brain/awab299. PMID: 34382076Free PMC Article
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Huber RJ
Dis Model Mech 2021 Dec 1;14(12) Epub 2021 Dec 6 doi: 10.1242/dmm.049152. PMID: 34870700Free PMC Article
Cooper JD, Mole SE
Biochim Biophys Acta Mol Basis Dis 2020 Sep 1;1866(9):165681. Epub 2020 Jan 8 doi: 10.1016/j.bbadis.2020.165681. PMID: 31926264
von Tetzchner S, Fosse P, Elmerskog B
Biochim Biophys Acta 2013 Nov;1832(11):1894-905. Epub 2013 Mar 5 doi: 10.1016/j.bbadis.2013.02.017. PMID: 23470553

Clinical prediction guides

Saleh MM, Hamhom AM, Al-Otaibi A, AlGhamdi M, Housawi Y, Aljadhai YI, Alameer S, Almannai M, Jad LA, Alwadei AH, Tabassum S, Alsaman A, AlAsmari A, Al Mutairi F, Althiyab H, Bashiri FA, AlHumaidi S, Alfadhel M, Mink JW, AlHashim A, Faqeih EA; Saudi NCL Study Consortium
Pediatr Neurol 2024 Jun;155:149-155. Epub 2024 Mar 7 doi: 10.1016/j.pediatrneurol.2024.03.004. PMID: 38653183
Munesue Y, Ageyama N, Kimura N, Takahashi I, Nakayama S, Okabayashi S, Katakai Y, Koie H, Yagami KI, Ishii K, Tamaoka A, Yasutomi Y, Shimozawa N
Exp Neurol 2023 May;363:114381. Epub 2023 Mar 12 doi: 10.1016/j.expneurol.2023.114381. PMID: 36918063
Huber RJ
Dis Model Mech 2021 Dec 1;14(12) Epub 2021 Dec 6 doi: 10.1242/dmm.049152. PMID: 34870700Free PMC Article
Lehwald LM, Pappa R, Steward S, de Los Reyes E
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Barohn RJ, Dowd DC, Kagan-Hallet KS
Pediatr Neurol 1992 Jan-Feb;8(1):54-9. doi: 10.1016/0887-8994(92)90054-3. PMID: 1558577

Recent systematic reviews

Quintas S, Sanles-Falagan R, Berbís MÁ
Mov Disord Clin Pract 2024 Jun;11(6):613-625. Epub 2024 May 1 doi: 10.1002/mdc3.14055. PMID: 38693679Free PMC Article
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Epilepsia 2024 Mar;65(3):709-724. Epub 2024 Jan 17 doi: 10.1111/epi.17880. PMID: 38231304
Mole SE, Schulz A, Badoe E, Berkovic SF, de Los Reyes EC, Dulz S, Gissen P, Guelbert N, Lourenco CM, Mason HL, Mink JW, Murphy N, Nickel M, Olaya JE, Scarpa M, Scheffer IE, Simonati A, Specchio N, Von Löbbecke I, Wang RY, Williams RE
Orphanet J Rare Dis 2021 Apr 21;16(1):185. doi: 10.1186/s13023-021-01813-5. PMID: 33882967Free PMC Article
Kuper WFE, van Alfen C, Rigterink RH, Fuchs SA, van Genderen MM, van Hasselt PM
J Inherit Metab Dis 2018 Mar;41(2):257-261. Epub 2018 Feb 1 doi: 10.1007/s10545-018-0143-x. PMID: 29392585Free PMC Article
Autti T, Joensuu R, Aberg L
Neuroradiology 2007 Jul;49(7):571-8. Epub 2007 Mar 3 doi: 10.1007/s00234-007-0220-6. PMID: 17334752

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