Format

Send to:

Choose Destination

Ceroid lipofuscinosis neuronal 1(CLN1)

MedGen UID:
340540
Concept ID:
C1850451
Disease or Syndrome
Synonyms: Adult CLN (type of CLN1); CEROID LIPOFUSCINOSIS, NEURONAL, 1, VARIABLE AGE AT ONSET; Classic late infantile CLN (type of CLN1); CLN1; CLN1 Disease; CLN1 variable age at onset; Infantile CLN (type of CLN1); Juvenile CLN (type of CLN1); Neuronal Ceroid-Lipofuscinoses; PPT1-Related Neuronal Ceroid-Lipofuscinosis
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). [HPO:curators]
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
 
Gene (location): PPT1 (1p34.2)
OMIM®: 256730
Orphanet: ORPHA228329

Definition

The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The lipopigment pattern seen most often in CLN1 is referred to as granular osmiophilic deposits (GROD). The patterns most often observed in CLN2 and CLN3 are 'curvilinear' and 'fingerprint' profiles, respectively. CLN4, CLN5, CLN6, CLN7, and CLN8 show mixed combinations of granular, curvilinear, fingerprint, and rectilinear profiles. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). Zeman and Dyken (1969) referred to these conditions as the 'neuronal ceroid lipofuscinoses.' Goebel (1995) provided a comprehensive review of the NCLs and noted that they are possibly the most common group of neurodegenerative diseases in children. Mole et al. (2005) provided a detailed clinical and genetic review of the neuronal ceroid lipofuscinoses. Genetic Heterogeneity of Neuronal Ceroid Lipofuscinosis See also CLN2 (204500), caused by mutation in the TPP1 gene (607998) on chromosome 11p15; CLN3 (204200), caused by mutation in the CLN3 gene (607042) on 16p12; CLN4A (204300), caused by mutation in the CLN6 gene (606725) on 15q21; CLN4B (162350), caused by mutation in the DNAJC5 gene (611203) on 20q13; CLN5 (256731), caused by mutation in the CLN5 gene (608102) on 13q; CLN6 (601780), caused by mutation in the CLN6 gene (602780) on 15q21; CLN7 (610951), caused by mutation in the MFSD8 gene (611124) on 4q28; CLN8 (600143) and the Northern epilepsy variant of CLN8 (610003), caused by mutation in the CLN8 gene (607837) on 8pter; CLN10 (610127), caused by mutation in the CTSD gene (116840) on 11p15; CLN11 (614706), caused by mutation in the GRN gene (138945) on 17q; CLN13 (615362), caused by mutation in the CTSF gene (603539) on 11q13; and CLN14 (611726), caused by mutation in the KCTD7 gene (611725) on 7q11. CLN9 (609055) has not been molecularly characterized. A disorder that was formerly designated neuronal ceroid lipofuscinosis-12 (CLN12) is now considered to be a variable form of Kufor-Rakeb syndrome (KRS; 606693). [from OMIM]

Additional description

From GHR
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, brain cells 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.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.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.  https://ghr.nlm.nih.gov/condition/cln1-disease

Clinical features

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- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Flexion contracture
MedGen UID:
3227
Concept ID:
C0009917
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Depressivity
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.
Hallucinations
MedGen UID:
6709
Concept ID:
C0018524
Mental or Behavioral Dysfunction
A false sensory perception in the absence of an external stimulus, as distinct from an illusion which is a misperception of an external stimulus.
Macular degeneration
MedGen UID:
7434
Concept ID:
C0024437
Disease or Syndrome
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells of the macula lutea.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
A condition of decreased tone of the skeletal muscles and diminished resistance to passive stretching.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A form of muscle hypertonia associated with upper MOTOR NEURON DISEASE. Resistance to passive stretch of a spastic muscle results in minimal initial resistance (a "free interval") followed by an incremental increase in muscle tone. Tone increases in proportion to the velocity of stretch. Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. (From Adams et al., Principles of Neurology, 6th ed, p54)
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Sign or Symptom
A rapid, involuntary jerk of a muscle or group of muscles.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
A disorder characterized by loss of optic nerve fibers. It may be inherited or acquired. Acquired causes include ischemia, optic nerve neuropathy, glaucoma, trauma, radiation, brain tumors, and multiple sclerosis. It leads to vision disturbances.
Seizures
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."
Sleep disturbance
MedGen UID:
52372
Concept ID:
C0037317
Sign or Symptom
An abnormality of sleep including such phenomena as 1) insomnia/hypersomnia, 2) non-restorative sleep, 3) sleep schedule disorder, 4) excessive daytime somnolence, 5) sleep apnea, and 6) restlessness.
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.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Finding
Blindness is the condition of lacking visual perception due to physiological or neurological factors.
Loss of speech
MedGen UID:
107445
Concept ID:
C0542223
Finding
Psychomotor deterioration
MedGen UID:
373191
Concept ID:
C1836842
Finding
Loss of previously present mental and motor abilities.
Decreased light- and dark-adapted electroretinogram amplitude
MedGen UID:
326793
Concept ID:
C1839025
Finding
Descreased amplitude of eletrical response upon electroretinography.
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Postnatal microcephaly
MedGen UID:
339779
Concept ID:
C1847514
Finding
Microcephaly (HP:0000252) with onset in the postnatal period, that is, the head circumference is in the normal range at birth but falls behind normal values later in development.
Progressive microcephaly
MedGen UID:
340542
Concept ID:
C1850456
Finding
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.
Undetectable electroretinogram
MedGen UID:
383742
Concept ID:
C1855685
Finding
Lack of any response to stimulation upon electroretinography.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
Feelings of annoyance, impatience, and anger.
Progressive visual loss
MedGen UID:
479327
Concept ID:
C3277697
Finding
A reduction of previously attained ability to see.
Increased neuronal autofluorescent lipopigment
MedGen UID:
866548
Concept ID:
C4020857
Finding
Lipofuscin, a generic term applied to autofluorescent lipopigment, is a mixture of protein and lipid that accumulates in most aging cells, particularly those involved in high lipid turnover (e.g., the adrenal medulla) or phagocytosis of other cell types (e g., the retinal pigment epithelium or RPE; macrophage). This term pertains if there is an increase in the neuronal accumulation of lipofuscin (also known as autofluorescent lipoprotein) more than expected for the age of the patient.
Cerebral atrophy
MedGen UID:
892664
Concept ID:
C4020860
Disease or Syndrome
Global developmental delay
MedGen UID:
892935
Concept ID:
C4020875
Pathologic Function
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.
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding

Recent clinical studies

Etiology

Chen FK, Zhang X, Eintracht J, Zhang D, Arunachalam S, Thompson JA, Chelva E, Mallon D, Chen SC, McLaren T, Lamey T, De Roach J, McLenachan S
Doc Ophthalmol 2019 Feb;138(1):55-70. Epub 2018 Nov 16 doi: 10.1007/s10633-018-9665-7. PMID: 30446867
Hosseini Bereshneh A, Garshasbi M
J Med Case Rep 2018 Sep 25;12(1):281. doi: 10.1186/s13256-018-1788-7. PMID: 30249282Free PMC Article
Sleat DE, Tannous A, Sohar I, Wiseman JA, Zheng H, Qian M, Zhao C, Xin W, Barone R, Sims KB, Moore DF, Lobel P
J Proteome Res 2017 Oct 6;16(10):3787-3804. Epub 2017 Aug 28 doi: 10.1021/acs.jproteome.7b00460. PMID: 28792770Free PMC Article
Specchio N, Bellusci M, Pietrafusa N, Trivisano M, de Palma L, Vigevano F
Epilepsia 2017 Aug;58(8):1380-1388. Epub 2017 Jun 20 doi: 10.1111/epi.13820. PMID: 28632327
Fietz M, AlSayed M, Burke D, Cohen-Pfeffer J, Cooper JD, Dvořáková L, Giugliani R, Izzo E, Jahnová H, Lukacs Z, Mole SE, Noher de Halac I, Pearce DA, Poupetova H, Schulz A, Specchio N, Xin W, Miller N
Mol Genet Metab 2016 Sep;119(1-2):160-7. Epub 2016 Jul 25 doi: 10.1016/j.ymgme.2016.07.011. PMID: 27553878

Diagnosis

Chen FK, Zhang X, Eintracht J, Zhang D, Arunachalam S, Thompson JA, Chelva E, Mallon D, Chen SC, McLaren T, Lamey T, De Roach J, McLenachan S
Doc Ophthalmol 2019 Feb;138(1):55-70. Epub 2018 Nov 16 doi: 10.1007/s10633-018-9665-7. PMID: 30446867
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
Specchio N, Bellusci M, Pietrafusa N, Trivisano M, de Palma L, Vigevano F
Epilepsia 2017 Aug;58(8):1380-1388. Epub 2017 Jun 20 doi: 10.1111/epi.13820. PMID: 28632327
Fietz M, AlSayed M, Burke D, Cohen-Pfeffer J, Cooper JD, Dvořáková L, Giugliani R, Izzo E, Jahnová H, Lukacs Z, Mole SE, Noher de Halac I, Pearce DA, Poupetova H, Schulz A, Specchio N, Xin W, Miller N
Mol Genet Metab 2016 Sep;119(1-2):160-7. Epub 2016 Jul 25 doi: 10.1016/j.ymgme.2016.07.011. PMID: 27553878
Saini AG, Sankhyan N, Singhi P
Pediatr Neurol 2016 Jul;60:75-8. Epub 2016 Mar 4 doi: 10.1016/j.pediatrneurol.2016.02.015. PMID: 27343025

Therapy

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
Levin SW, Baker EH, Zein WM, Zhang Z, Quezado ZM, Miao N, Gropman A, Griffin KJ, Bianconi S, Chandra G, Khan OI, Caruso RC, Liu A, Mukherjee AB
Lancet Neurol 2014 Aug;13(8):777-87. Epub 2014 Jul 2 doi: 10.1016/S1474-4422(14)70142-5. PMID: 24997880Free PMC Article
Katz ML, Coates JR, Sibigtroth CM, Taylor JD, Carpentier M, Young WM, Wininger FA, Kennedy D, Vuillemenot BR, O'Neill CA
J Neurosci Res 2014 Nov;92(11):1591-8. Epub 2014 Jun 17 doi: 10.1002/jnr.23423. PMID: 24938720Free PMC Article

Prognosis

Chen FK, Zhang X, Eintracht J, Zhang D, Arunachalam S, Thompson JA, Chelva E, Mallon D, Chen SC, McLaren T, Lamey T, De Roach J, McLenachan S
Doc Ophthalmol 2019 Feb;138(1):55-70. Epub 2018 Nov 16 doi: 10.1007/s10633-018-9665-7. PMID: 30446867
Parviainen L, Dihanich S, Anderson GW, Wong AM, Brooks HR, Abeti R, Rezaie P, Lalli G, Pope S, Heales SJ, Mitchison HM, Williams BP, Cooper JD
Acta Neuropathol Commun 2017 Oct 17;5(1):74. doi: 10.1186/s40478-017-0476-y. PMID: 29041969Free PMC Article
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
Levin SW, Baker EH, Zein WM, Zhang Z, Quezado ZM, Miao N, Gropman A, Griffin KJ, Bianconi S, Chandra G, Khan OI, Caruso RC, Liu A, Mukherjee AB
Lancet Neurol 2014 Aug;13(8):777-87. Epub 2014 Jul 2 doi: 10.1016/S1474-4422(14)70142-5. PMID: 24997880Free PMC Article
Kamate M, Prashanth GP, Hattiholi V
Neurol India 2012 May-Jun;60(3):316-20. doi: 10.4103/0028-3886.98524. PMID: 22824694

Clinical prediction guides

Chen FK, Zhang X, Eintracht J, Zhang D, Arunachalam S, Thompson JA, Chelva E, Mallon D, Chen SC, McLaren T, Lamey T, De Roach J, McLenachan S
Doc Ophthalmol 2019 Feb;138(1):55-70. Epub 2018 Nov 16 doi: 10.1007/s10633-018-9665-7. PMID: 30446867
Hosseini Bereshneh A, Garshasbi M
J Med Case Rep 2018 Sep 25;12(1):281. doi: 10.1186/s13256-018-1788-7. PMID: 30249282Free PMC Article
Parviainen L, Dihanich S, Anderson GW, Wong AM, Brooks HR, Abeti R, Rezaie P, Lalli G, Pope S, Heales SJ, Mitchison HM, Williams BP, Cooper JD
Acta Neuropathol Commun 2017 Oct 17;5(1):74. doi: 10.1186/s40478-017-0476-y. PMID: 29041969Free PMC Article
Sleat DE, Tannous A, Sohar I, Wiseman JA, Zheng H, Qian M, Zhao C, Xin W, Barone R, Sims KB, Moore DF, Lobel P
J Proteome Res 2017 Oct 6;16(10):3787-3804. Epub 2017 Aug 28 doi: 10.1021/acs.jproteome.7b00460. PMID: 28792770Free PMC Article
Ragbeer SN, Augustine EF, Mink JW, Thatcher AR, Vierhile AE, Adams HR
J Child Neurol 2016 Mar;31(4):481-7. Epub 2015 Sep 2 doi: 10.1177/0883073815600863. PMID: 26336202Free PMC Article

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center