Format

Send to:

Choose Destination

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
Source: HPO
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).
autosomal recessive
MedGen UID:
832197
Concept ID:
CN227382
Intellectual Product
Source: Orphanet
Describes a disorder in which two mutated alleles located on one of the 22 autosomes (non-sex chromosomes) are necessary to express the phenotype and which carries a 25% risk of being passed on to offspring.
 
Gene (location): CLN5 (13q22.3)
OMIM®: 256731
Orphanet: ORPHA228360

Disease characteristics

Excerpted from the GeneReview: Neuronal Ceroid-Lipofuscinoses
The neuronal ceroid-lipofuscinoses (NCLs) are a group of inherited, neurodegenerative, lysosomal storage disorders characterized by progressive intellectual and motor deterioration, seizures, and early death. Visual loss is a feature of most forms. Clinical phenotypes have been characterized traditionally according to the age of onset and order of appearance of clinical features into infantile, late-infantile, juvenile, adult, and Northern epilepsy (also known as progressive epilepsy with mental retardation [EPMR]). There is however genetic and allelic heterogeneity; a proposed new nomenclature and classification system has been developed to take into account both the responsible gene and the age at disease onset; for example, CLN1 disease, infantile onset and CLN1 disease, juvenile onset are both caused by pathogenic variants in PPT1 but with differing age of onset. The most prevalent NCLs are CLN3 disease, classic juvenile and CLN2 disease, classic late infantile (although prevalence varies by ethnicity and country of family origin): CLN2 disease, classic late infantile. The first symptoms typically appear between age two and four years, usually starting with epilepsy, followed by regression of developmental milestones, myoclonic ataxia, and pyramidal signs. Visual impairment typically appears at age four to six years and rapidly progresses to light /dark awareness only. Life expectancy ranges from age six years to early teenage. CLN3 disease, classic juvenile. Onset is usually between ages four and ten years. Rapidly progressing visual loss resulting in severe visual impairment within one to two years is often the first clinical sign. Epilepsy with generalized tonic-clonic seizures and/or complex-partial seizures typically appears around age ten years. Life expectancy ranges from the late teens to the 30s. Other forms of NCL may present with behavior changes, epilepsy, visual impairment, or slowing of developmental progress and then loss of skills. The course may be extremely variable. Some genotype-phenotype information is available. [from GeneReviews]
Authors:
Sara E Mole  |  Ruth E Williams   view full author information

Additional descriptions

From OMIM
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).  http://www.omim.org/entry/256731
From GHR
Late-infantile neuronal ceroid lipofuscinosis (NCL) is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition typically begin in late infancy or early childhood. The initial features usually include recurrent seizures (epilepsy) and difficulty coordinating movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision impairment. Late-infantile NCL affects motor skills, such as sitting and walking, and speech development. This condition also causes the loss of previously acquired skills (developmental regression), progressive intellectual disability, 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.Late-infantile NCL is one of a group of NCLs (collectively called Batten disease) that affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. The different types of NCLs are distinguished by the age at which signs and symptoms first appear.  http://ghr.nlm.nih.gov/condition/late-infantile-neuronal-ceroid-lipofuscinosis

Clinical features

Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Retinal degeneration
MedGen UID:
48432
Concept ID:
C0035304
Finding
A retrogressive pathological change in the retina, focal or generalized, caused by genetic defects, inflammation, trauma, vascular disease, or aging. Degeneration affecting predominantly the macula lutea of the retina is MACULAR DEGENERATION. (Newell, Ophthalmology: Principles and Concepts, 7th ed, p304)
Progressive visual loss
MedGen UID:
326867
Concept ID:
C1839364
Finding
A reduction of previously attained ability to see.
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.
Seizure Disorders
MedGen UID:
4506
Concept ID:
C0014544
Disease or Syndrome
Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters of nerve cells, or neurons, in the brain send out the wrong signals. People may have strange sensations and emotions or behave strangely. They may have violent muscle spasms or lose consciousness. Epilepsy has many possible causes, including illness, brain injury, and abnormal brain development. In many cases, the cause is unknown. Doctors use brain scans and other tests to diagnose epilepsy. It is important to start treatment right away. There is no cure for epilepsy, but medicines can control seizures for most people. When medicines are not working well, surgery or implanted devices such as vagus nerve stimulators may help. Special diets can help some children with epilepsy. NIH: National Institute of Neurological Disorders and Stroke.
Intellectual functioning disability
MedGen UID:
7544
Concept ID:
C0025362
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Sign or Symptom
Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some CENTRAL NERVOUS SYSTEM DISEASES; (e.g., EPILEPSY, MYOCLONIC). Nocturnal myoclonus is the principal feature of the NOCTURNAL MYOCLONUS SYNDROME. (From Adams et al., Principles of Neurology, 6th ed, pp102-3).
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.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Atrophy (wasting) of the cerebellum.
Developmental regression
MedGen UID:
373115
Concept ID:
C1836550
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.
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.
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.
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 profiles ultrastructurally in cells
MedGen UID:
323011
Concept ID:
C1836852
Finding
An intracellular accumulation of autofluorescent lipopigment storage material in a curved pattern.
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.

Recent clinical studies

Etiology

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. [Epub ahead of print] 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. [Epub ahead of print] PMID: 25205113Free PMC Article
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. [Epub ahead of print] 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. [Epub ahead of print] PMID: 24411222
Pérez-Poyato MS, Marfa MP, Abizanda IF, Rodriguez-Revenga L, Sánchez VC, González MJ, Puñal JE, Pérez AV, González MM, Bermejo AM, Hernández EM, Rosell MJ, Gort L, Milá M
J Child Neurol 2013 Apr;28(4):470-8. Epub 2012 Jul 25 doi: 10.1177/0883073812448459. [Epub ahead of print] PMID: 22832778

Diagnosis

Craiu D, Dragostin O, Dica A, Hoffman-Zacharska D, Gos M, Bastian AE, Gherghiceanu M, Rolfs A, Nahavandi N, Craiu M, Iliescu C
Eur J Paediatr Neurol 2015 Jan;19(1):78-86. Epub 2014 Aug 7 doi: 10.1016/j.ejpn.2014.07.008. [Epub ahead of print] PMID: 25439737
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. [Epub ahead of print] PMID: 25270050
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. [Epub ahead of print] PMID: 23768618
Pérez-Poyato MS, Marfa MP, Abizanda IF, Rodriguez-Revenga L, Sánchez VC, González MJ, Puñal JE, Pérez AV, González MM, Bermejo AM, Hernández EM, Rosell MJ, Gort L, Milá M
J Child Neurol 2013 Apr;28(4):470-8. Epub 2012 Jul 25 doi: 10.1177/0883073812448459. [Epub ahead of print] PMID: 22832778
Kamate M, Prashanth GP, Hattiholi V
Neurol India 2012 May-Jun;60(3):316-20. doi: 10.4103/0028-3886.98524. PMID: 22824694

Therapy

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. [Epub ahead of print] 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. [Epub ahead of print] 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. [Epub ahead of print] 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. [Epub ahead of print] PMID: 24411222
Sondhi D, Johnson L, Purpura K, Monette S, Souweidane MM, Kaplitt MG, Kosofsky B, Yohay K, Ballon D, Dyke J, Kaminksy SM, Hackett NR, Crystal RG
Hum Gene Ther Methods 2012 Oct;23(5):324-35. Epub 2012 Nov 6 doi: 10.1089/hgtb.2012.120. [Epub ahead of print] PMID: 23131032Free PMC Article

Prognosis

Canafoglia L, Gilioli I, Invernizzi F, Sofia V, Fugnanesi V, Morbin M, Chiapparini L, Granata T, Binelli S, Scaioli V, Garavaglia B, Nardocci N, Berkovic SF, Franceschetti S
Neurology 2015 Jul 28;85(4):316-24. Epub 2015 Jun 26 doi: 10.1212/WNL.0000000000001784. [Epub ahead of print] PMID: 26115733Free PMC Article
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. [Epub ahead of print] 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. [Epub ahead of print] PMID: 24411222
Pérez-Poyato MS, Marfa MP, Abizanda IF, Rodriguez-Revenga L, Sánchez VC, González MJ, Puñal JE, Pérez AV, González MM, Bermejo AM, Hernández EM, Rosell MJ, Gort L, Milá M
J Child Neurol 2013 Apr;28(4):470-8. Epub 2012 Jul 25 doi: 10.1177/0883073812448459. [Epub ahead of print] PMID: 22832778
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

Barney CC, Hoch J, Byiers B, Dimian A, Symons FJ
Clin J Pain 2015 Nov;31(11):998-1003. doi: 10.1097/AJP.0000000000000192. PMID: 25569218Free 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. [Epub ahead of print] PMID: 24411222
Santorelli FM, Garavaglia B, Cardona F, Nardocci N, Bernardina BD, Sartori S, Suppiej A, Bertini E, Claps D, Battini R, Biancheri R, Filocamo M, Pezzini F, Simonati A
Orphanet J Rare Dis 2013 Feb 2;8:19. doi: 10.1186/1750-1172-8-19. [Epub ahead of print] PMID: 23374165Free PMC Article
Dyke JP, Sondhi D, Voss HU, Shungu DC, Mao X, Yohay K, Worgall S, Hackett NR, Hollmann C, Yeotsas ME, Jeong AL, Van de Graaf B, Cao I, Kaminsky SM, Heier LA, Rudser KD, Souweidane MM, Kaplitt MG, Kosofsky B, Crystal RG, Ballon D
AJNR Am J Neuroradiol 2013 Apr;34(4):884-9. Epub 2012 Oct 4 doi: 10.3174/ajnr.A3297. [Epub ahead of print] PMID: 23042927Free PMC Article
Hu J, Lu JY, Wong AM, Hynan LS, Birnbaum SG, Yilmaz DS, Streit BM, Lenartowicz EM, Thompson TC, Cooper JD, Hofmann SL
Mol Genet Metab 2012 Sep;107(1-2):213-21. Epub 2012 May 22 doi: 10.1016/j.ymgme.2012.05.009. [Epub ahead of print] PMID: 22704978Free PMC Article

Recent systematic reviews

Vadlamudi L, Westmoreland BF, Klass DW, Parisi JE
Clin Neurophysiol 2003 Sep;114(9):1738-43. PMID: 12948804
Ruchoux MM, Goebel HH
Neuropathol Appl Neurobiol 1997 Jun;23(3):262-3. PMID: 9223136

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...