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Neuronal ceroid lipofuscinosis 13(CLN13)

MedGen UID:
811566
Concept ID:
C3715049
Disease or Syndrome
Synonym: CEROID LIPOFUSCINOSIS, NEURONAL, 13 (KUFS TYPE)
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).
 
Gene (location): CTSF (11q13.2)
 
Monarch Initiative: MONDO:0014147
OMIM®: 615362
Orphanet: ORPHA352709

Definition

Neuronal ceroid lipofuscinosis-13 (CLN13) is an autosomal recessive neurodegenerative disorder characterized by adult onset of progressive cognitive decline and motor dysfunction leading to dementia and often early death. Some patients develop seizures. Neurons show abnormal accumulation of autofluorescent material (summary by Smith et al., 2013). Adult-onset neuronal ceroid lipofuscinosis is sometimes referred to as Kufs disease (see 204300). In a review of the classification of CLN disease, Gardner and Mole (2021) noted that the CLN13 phenotype corresponds to 'Kufs type B', which is characterized by dementia and a variety of motor signs (Smith et al., 2013). For a discussion of genetic heterogeneity of neuronal ceroid lipofuscinosis (CLN), see CLN1 (256730). [from OMIM]

Clinical features

From HPO
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).
Confusion
MedGen UID:
3587
Concept ID:
C0009676
Mental or Behavioral Dysfunction
Lack of clarity and coherence of thought, perception, understanding, or action.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Abnormality of extrapyramidal motor function
MedGen UID:
115941
Concept ID:
C0234133
Sign or Symptom
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
Mental deterioration
MedGen UID:
66713
Concept ID:
C0234985
Mental or Behavioral Dysfunction
Loss of previously present mental abilities, generally in adults.
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.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Diffuse cerebral atrophy
MedGen UID:
108958
Concept ID:
C0598275
Finding
Diffuse unlocalised atrophy affecting the cerebrum.
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.
Focal-onset seizure
MedGen UID:
199670
Concept ID:
C0751495
Disease or Syndrome
A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Primitive reflex
MedGen UID:
333065
Concept ID:
C1838319
Finding
The primitive reflexes are a group of behavioral motor responses which are found in normal early development, are subsequently inhibited, but may be released from inhibition by cerebral, usually frontal, damage. They are thus part of a broader group of reflexes which reflect release phenomena, such as exaggerated stretch reflexes and extensor plantars. They do however involve more complex motor responses than such simple stretch reflexes, and are often a normal feature in the neonate or infant.
Neuronal loss in central nervous system
MedGen UID:
342515
Concept ID:
C1850496
Finding
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.

Term Hierarchy

Professional guidelines

PubMed

De BP, Rosenberg JB, Selvan N, Wilson I, Yusufzai N, Greco A, Kaminsky SM, Heier LA, Ricart Arbona RJ, Miranda IC, Monette S, Nair A, Khanna R, Crystal RG, Sondhi D
Hum Gene Ther 2023 Sep;34(17-18):905-916. doi: 10.1089/hum.2023.067. PMID: 37624739Free PMC Article
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
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

Recent clinical studies

Etiology

Schulz A, Specchio N, de Los Reyes E, Gissen P, Nickel M, Trivisano M, Aylward SC, Chakrapani A, Schwering C, Wibbeler E, Westermann LM, Ballon DJ, Dyke JP, Cherukuri A, Bondade S, Slasor P, Cohen Pfeffer J
Lancet Neurol 2024 Jan;23(1):60-70. doi: 10.1016/S1474-4422(23)00384-8. PMID: 38101904
Huber RJ
Dis Model Mech 2021 Dec 1;14(12) Epub 2021 Dec 6 doi: 10.1242/dmm.049152. PMID: 34870700Free PMC Article
Liu W, Kleine-Holthaus SM, Herranz-Martin S, Aristorena M, Mole SE, Smith AJ, Ali RR, Rahim AA
Biochim Biophys Acta Mol Basis Dis 2020 Sep 1;1866(9):165772. Epub 2020 Mar 24 doi: 10.1016/j.bbadis.2020.165772. PMID: 32220628
Johnson TB, Cain JT, White KA, Ramirez-Montealegre D, Pearce DA, Weimer JM
Nat Rev Neurol 2019 Mar;15(3):161-178. doi: 10.1038/s41582-019-0138-8. PMID: 30783219Free PMC Article
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

Diagnosis

Huber RJ
Dis Model Mech 2021 Dec 1;14(12) Epub 2021 Dec 6 doi: 10.1242/dmm.049152. PMID: 34870700Free 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
Johnson TB, Cain JT, White KA, Ramirez-Montealegre D, Pearce DA, Weimer JM
Nat Rev Neurol 2019 Mar;15(3):161-178. doi: 10.1038/s41582-019-0138-8. PMID: 30783219Free PMC Article
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
Martin JJ
Dev Neurosci 1991;13(4-5):331-8. doi: 10.1159/000112182. PMID: 1817040

Therapy

Schulz A, Specchio N, de Los Reyes E, Gissen P, Nickel M, Trivisano M, Aylward SC, Chakrapani A, Schwering C, Wibbeler E, Westermann LM, Ballon DJ, Dyke JP, Cherukuri A, Bondade S, Slasor P, Cohen Pfeffer J
Lancet Neurol 2024 Jan;23(1):60-70. doi: 10.1016/S1474-4422(23)00384-8. PMID: 38101904
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
Kauss V, Dambrova M, Medina DL
Biochim Biophys Acta Mol Basis Dis 2020 Sep 1;1866(9):165553. Epub 2019 Sep 12 doi: 10.1016/j.bbadis.2019.165553. PMID: 31521819
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
Kohlschütter A, Schulz A
Pediatr Endocrinol Rev 2016 Jun;13 Suppl 1:682-8. PMID: 27491216

Prognosis

Panjeshahi S, Karimzadeh P, Movafagh A, Ahmadabadi F, Rahimian E, Alijanpour S, Miryounesi M
Hum Genet 2023 Aug;142(8):1001-1016. Epub 2023 Apr 19 doi: 10.1007/s00439-023-02556-y. PMID: 37074398
Huber RJ
Dis Model Mech 2021 Dec 1;14(12) Epub 2021 Dec 6 doi: 10.1242/dmm.049152. PMID: 34870700Free PMC Article
Abreu NJ, de Los Reyes EC
Eur J Paediatr Neurol 2021 Nov;35:A2. Epub 2021 Nov 17 doi: 10.1016/j.ejpn.2021.11.007. PMID: 34844861
Pérez-Poyato MS, Milà Recansens M, Ferrer Abizanda I, Montero Sánchez R, Rodríguez-Revenga L, Cusí Sánchez V, García González MM, Domingo Jiménez R, Camino León R, Velázquez Fragua R, Martínez-Bermejo A, Pineda Marfà M
J Inherit Metab Dis 2011 Oct;34(5):1083-93. Epub 2011 Apr 16 doi: 10.1007/s10545-011-9323-7. PMID: 21499717
Valadares ER, Pizarro MX, Oliveira LR, Amorim RH, Pinheiro TM, Grieben U, Santos HH, Queiroz RR, Lopes Gde C, Godard AL
Arq Neuropsiquiatr 2011 Feb;69(1):13-8. doi: 10.1590/s0004-282x2011000100004. PMID: 21359416

Clinical prediction guides

Schulz A, Specchio N, de Los Reyes E, Gissen P, Nickel M, Trivisano M, Aylward SC, Chakrapani A, Schwering C, Wibbeler E, Westermann LM, Ballon DJ, Dyke JP, Cherukuri A, Bondade S, Slasor P, Cohen Pfeffer J
Lancet Neurol 2024 Jan;23(1):60-70. doi: 10.1016/S1474-4422(23)00384-8. PMID: 38101904
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
Badilla-Porras R, Echeverri-McCandless A, Weimer JM, Ulate-Campos A, Soto-Rodríguez A, Gutiérrez-Mata A, Hernández-Con L, Bogantes-Ledezma S, Balmaceda-Meza A, Brudvig J, Sanabria-Castro A
Orphanet J Rare Dis 2022 Jan 10;17(1):13. doi: 10.1186/s13023-021-02162-z. PMID: 35012600Free 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
Valadares ER, Pizarro MX, Oliveira LR, Amorim RH, Pinheiro TM, Grieben U, Santos HH, Queiroz RR, Lopes Gde C, Godard AL
Arq Neuropsiquiatr 2011 Feb;69(1):13-8. doi: 10.1590/s0004-282x2011000100004. PMID: 21359416

Recent systematic reviews

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

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