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Infantile neuronal ceroid lipofuscinosis(INCL)

MedGen UID:
75666
Concept ID:
C0268281
Disease or Syndrome
Synonyms: INCL; SANTAVUORI DISEASE; SANTAVUORI-HALTIA DISEASE
SNOMED CT: Hagberg-Santavouri type neuronal ceroid lipofuscinosis (58258004); Polyunsaturated fatty acid lipidosis (58258004); Haltia-Santavouri type neuronal ceroid lipofuscinosis (58258004); Infantile neuronal ceroid lipofuscinosis (58258004); Hagberg-Santavuori disease (58258004); Polyunsaturated acid lipidosis (58258004)
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:0019261
OMIM®: 256730
Orphanet: ORPHA79263

Definition

CLN1 disease is an inherited disorder that primarily affects the nervous system. Individuals with this condition have normal development in infancy, but typically by 18 months they become increasingly irritable and begin to lose previously acquired skills (developmental regression). In affected children, nerve cells in the brain die over time, leading to an overall loss of brain tissue (brain atrophy) and an unusually small head (microcephaly). Children with CLN1 disease have decreased muscle tone (hypotonia), intellectual and motor disability, and rarely are able to speak or walk. Some affected children develop repetitive hand movements. By age 2, individuals with this condition often have muscle twitches (myoclonus), recurrent seizures (epilepsy), and vision loss. Some affected children develop frequent respiratory infections. As the condition worsens, children have severe feeding difficulties that often require a feeding tube. Children with CLN1 disease usually do not survive past childhood.

CLN1 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 people with CLN1 disease do not develop symptoms until later in childhood or in adulthood. As with younger affected children, older individuals develop a decline in intellectual function, myoclonus, epilepsy, and vision loss. In these individuals, life expectancy depends on when signs and symptoms of CLN1 disease develop and their severity; affected individuals may survive only into adolescence or through adulthood. Adults with CLN1 disease may also have movement disorders, including impaired muscle coordination (ataxia) or a pattern of movement abnormalities known as parkinsonism. [from MedlinePlus Genetics]

Professional guidelines

PubMed

Augustine EF, Adams HR, de Los Reyes E, Drago K, Frazier M, Guelbert N, Laine M, Levin T, Mink JW, Nickel M, Peifer D, Schulz A, Simonati A, Topcu M, Turunen JA, Williams R, Wirrell EC, King S
Pediatr Neurol 2021 Jul;120:38-51. Epub 2021 Apr 9 doi: 10.1016/j.pediatrneurol.2021.04.002. PMID: 34000449
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
Santavuori P, Vanhanen SL, Sainio K, Nieminen M, Wallden T, Launes J, Raininko R
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Recent clinical studies

Etiology

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
Baker EH, Levin SW, Zhang Z, Mukherjee AB
AJNR Am J Neuroradiol 2017 Feb;38(2):376-382. Epub 2016 Oct 20 doi: 10.3174/ajnr.A4978. PMID: 27765741Free PMC Article
Miller JN, Kovács AD, Pearce DA
Hum Mol Genet 2015 Jan 1;24(1):185-96. Epub 2014 Sep 8 doi: 10.1093/hmg/ddu428. PMID: 25205113Free PMC Article
Hawkins-Salsbury JA, Cooper JD, Sands MS
Biochim Biophys Acta 2013 Nov;1832(11):1906-9. Epub 2013 Jun 6 doi: 10.1016/j.bbadis.2013.05.026. PMID: 23747979Free 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
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
Hawkins-Salsbury JA, Cooper JD, Sands MS
Biochim Biophys Acta 2013 Nov;1832(11):1906-9. Epub 2013 Jun 6 doi: 10.1016/j.bbadis.2013.05.026. PMID: 23747979Free PMC Article
Goebel HH
J Child Neurol 1995 Nov;10(6):424-37. doi: 10.1177/088307389501000602. PMID: 8576551

Therapy

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
Baker EH, Levin SW, Zhang Z, Mukherjee AB
AJNR Am J Neuroradiol 2017 Feb;38(2):376-382. Epub 2016 Oct 20 doi: 10.3174/ajnr.A4978. PMID: 27765741Free PMC Article
Kohlschütter A, Schulz A
Pediatr Endocrinol Rev 2016 Jun;13 Suppl 1:682-8. PMID: 27491216
Miller JN, Kovács AD, Pearce DA
Hum Mol Genet 2015 Jan 1;24(1):185-96. Epub 2014 Sep 8 doi: 10.1093/hmg/ddu428. PMID: 25205113Free PMC Article
Sondhi D, Hackett NR, Apblett RL, Kaminsky SM, Pergolizzi RG, Crystal RG
Arch Neurol 2001 Nov;58(11):1793-8. doi: 10.1001/archneur.58.11.1793. PMID: 11708986

Prognosis

Augustine EF, Adams HR, de Los Reyes E, Drago K, Frazier M, Guelbert N, Laine M, Levin T, Mink JW, Nickel M, Peifer D, Schulz A, Simonati A, Topcu M, Turunen JA, Williams R, Wirrell EC, King S
Pediatr Neurol 2021 Jul;120:38-51. Epub 2021 Apr 9 doi: 10.1016/j.pediatrneurol.2021.04.002. PMID: 34000449
Baker EH, Levin SW, Zhang Z, Mukherjee AB
AJNR Am J Neuroradiol 2017 Feb;38(2):376-382. Epub 2016 Oct 20 doi: 10.3174/ajnr.A4978. PMID: 27765741Free PMC Article
Turnbull J, Girard JM, Lohi H, Chan EM, Wang P, Tiberia E, Omer S, Ahmed M, Bennett C, Chakrabarty A, Tyagi A, Liu Y, Pencea N, Zhao X, Scherer SW, Ackerley CA, Minassian BA
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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

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
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
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
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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