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Ceroid lipofuscinosis neuronal 5(CLN5)

MedGen UID:
376792
Concept ID:
C1850442
Disease or Syndrome
Synonyms: CEROID LIPOFUSCINOSIS, NEURONAL, 5, VARIABLE AGE AT ONSET; CLN5; CLN5 Disease; CLN5-Related Neuronal Ceroid-Lipofuscinosis; Neuronal ceroid lipofuscinosis Finnish variant; NEURONAL CEROID LIPOFUSCINOSIS, LATE INFANTILE, FINNISH VARIANT; Neuronal Ceroid-Lipofuscinoses
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): CLN5 (13q22.3)
OMIM®: 256731
Orphanet: ORPHA228360

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 patterns observed most often in CLN5 comprise mixed combinations of 'granular,' 'curvilinear,' and 'fingerprint' profiles. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730). [from OMIM]

Additional description

From GHR
CLN5 disease is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition can begin anytime between childhood and early adulthood, but they typically appear around age 5. Children with CLN5 disease often have normal development until they experience the first signs of the condition, which are usually problems with movement and a loss of previously acquired motor skills (developmental regression). Other features of the condition include recurrent seizures that involve uncontrollable muscle jerks (myoclonic epilepsy), difficulty coordinating movements (ataxia), vision loss, and a decline in intellectual function. The life expectancy of people with CLN5 disease varies; affected individuals usually survive into adolescence or mid-adulthood.CLN5 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/cln5-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).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from CRANIAL NERVE DISEASES; NEUROMUSCULAR DISEASES; CEREBELLAR DISEASES; BASAL GANGLIA DISEASES; BRAIN STEM diseases; or diseases of the corticobulbar tracts (see PYRAMIDAL TRACTS). The cortical language centers are intact in this condition. (From Adams et al., Principles of Neurology, 6th ed, p489)
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Sign or Symptom
A rapid, involuntary jerk of a muscle or group of muscles.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. (Adams et al., Principles of Neurology, 6th ed, p272)
Retinal degeneration
MedGen UID:
48432
Concept ID:
C0035304
Finding
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells.
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."
Clumsiness
MedGen UID:
66690
Concept ID:
C0233844
Sign or Symptom
Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Dysdiadochokinesis
MedGen UID:
115975
Concept ID:
C0234979
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to perform rapidly alternating movements, such as rhythmically tapping the fingers on the knee.
Fingerprint intracellular accumulation of autofluorescent lipopigment storage material
MedGen UID:
324619
Concept ID:
C1836851
Finding
An intracellular accumulation of autofluorescent lipopigment storage material in a trabecular or fingerprint-like pattern.
Curvilinear intracellular accumulation of autofluorescent lipopigment storage material
MedGen UID:
323011
Concept ID:
C1836852
Finding
An intracellular accumulation of autofluorescent lipopigment storage material in a curved pattern.
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Rectilinear intracellular accumulation of autofluorescent lipopigment storage material
MedGen UID:
338055
Concept ID:
C1850447
Finding
An intracellular accumulation of autofluorescent lipopigment storage material in a straight or rectilinear pattern.
Developmental regression
MedGen UID:
381534
Concept ID:
C1855009
Finding
Loss of developmental skills, as manifested by loss of developmental milestones.
Motor deterioration
MedGen UID:
356495
Concept ID:
C1866284
Finding
Loss of previously present motor (i.e., movement) abilities.
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.
Cerebellar atrophy
MedGen UID:
892891
Concept ID:
C4020873
Disease or Syndrome
Atrophy (wasting) of the cerebellum.
Abnormal nervous system electrophysiology
MedGen UID:
867410
Concept ID:
C4021781
Pathologic Function
An abnormality of the function of the electrical signals with which nerve cells communicate with each other or with muscles as measured by electrophysiological investigations.

Recent clinical studies

Etiology

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
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
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
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
Tokola AM, Salli EK, Åberg LE, Autti TH
Pediatr Neurol 2014 Feb;50(2):158-63. Epub 2013 Oct 30 doi: 10.1016/j.pediatrneurol.2013.10.013. PMID: 24411222

Diagnosis

Kozina AA, Okuneva EG, Baryshnikova NV, Krasnenko AY, Tsukanov KY, Klimchuk OI, Kondakova OB, Larionova AN, Batysheva TT, Surkova EI, Shatalov PA, Ilinsky VV
BMC Med Genet 2018 Aug 25;19(1):151. doi: 10.1186/s12881-018-0669-7. PMID: 30144815Free 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
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
Nolte A, Bello A, Drögemüller M, Leeb T, Brockhaus E, Baumgärtner W, Wohlsein P
Tierarztl Prax Ausg K Kleintiere Heimtiere 2016 Dec 5;44(6):431-437. Epub 2016 Oct 25 doi: 10.15654/TPK-150766. PMID: 27778018
Shen J, Cram DS, Wu W, Cai L, Yang X, Sun X, Cui Y, Liu J
Reprod Biomed Online 2013 Aug;27(2):176-83. Epub 2013 May 4 doi: 10.1016/j.rbmo.2013.04.011. PMID: 23768618

Therapy

Bosch ME, Aldrich A, Fallet R, Odvody J, Burkovetskaya M, Schuberth K, Fitzgerald JA, Foust KD, Kielian T
J Neurosci 2016 Sep 14;36(37):9669-82. doi: 10.1523/JNEUROSCI.1635-16.2016. PMID: 27629717
Lu JY, Nelvagal HR, Wang L, Birnbaum SG, Cooper JD, Hofmann SL
Mol Genet Metab 2015 Sep-Oct;116(1-2):98-105. Epub 2015 May 12 doi: 10.1016/j.ymgme.2015.05.005. PMID: 25982063
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
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
Tokola AM, Salli EK, Åberg LE, Autti TH
Pediatr Neurol 2014 Feb;50(2):158-63. Epub 2013 Oct 30 doi: 10.1016/j.pediatrneurol.2013.10.013. PMID: 24411222

Prognosis

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
Simonati A, Williams RE, Nardocci N, Laine M, Battini R, Schulz A, Garavaglia B, Moro F, Pezzini F, Santorelli FM
Dev Med Child Neurol 2017 Aug;59(8):815-821. Epub 2017 May 25 doi: 10.1111/dmcn.13473. PMID: 28542837
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
Tokola AM, Salli EK, Åberg LE, Autti TH
Pediatr Neurol 2014 Feb;50(2):158-63. Epub 2013 Oct 30 doi: 10.1016/j.pediatrneurol.2013.10.013. PMID: 24411222
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

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
Simonati A, Williams RE, Nardocci N, Laine M, Battini R, Schulz A, Garavaglia B, Moro F, Pezzini F, Santorelli FM
Dev Med Child Neurol 2017 Aug;59(8):815-821. Epub 2017 May 25 doi: 10.1111/dmcn.13473. PMID: 28542837
Bosch ME, Aldrich A, Fallet R, Odvody J, Burkovetskaya M, Schuberth K, Fitzgerald JA, Foust KD, Kielian T
J Neurosci 2016 Sep 14;36(37):9669-82. doi: 10.1523/JNEUROSCI.1635-16.2016. PMID: 27629717
Tokola AM, Salli EK, Åberg LE, Autti TH
Pediatr Neurol 2014 Feb;50(2):158-63. Epub 2013 Oct 30 doi: 10.1016/j.pediatrneurol.2013.10.013. PMID: 24411222

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