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Cobblestone lissencephaly without muscular or ocular involvement(LIS5)

MedGen UID:
767571
Concept ID:
C3554657
Disease or Syndrome
Synonym: Lissencephaly 5
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): LAMB1 (7q31.1)
 
Monarch Initiative: MONDO:0014077
OMIM®: 615191
Orphanet: ORPHA352682

Definition

Lissencephaly-5 (LIS5) is an autosomal recessive brain malformation characterized by cobblestone changes in the cortex, more severe in the posterior region, and subcortical band heterotopia. Affected individuals have hydrocephalus, seizures, and severely delayed psychomotor development (Radmanesh et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432). [from OMIM]

Clinical features

From HPO
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Occipital encephalocele
MedGen UID:
4935
Concept ID:
C0014067
Congenital Abnormality
A type of encephalocele (that is, a a protrusion of part of the cranial contents including brain tissue through a congenital opening in the cranium, typically covered with skin or mucous membrane) in the occipital region of the skull. Occipital encephalocele presents as a midline swelling over the occipital bone. It is usually covered with normal full-thickness scalp.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
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.
Spastic paraplegia
MedGen UID:
20882
Concept ID:
C0037772
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Gray matter heterotopia
MedGen UID:
452349
Concept ID:
C0266491
Finding
Heterotopia or neuronal heterotopia are macroscopic clusters of misplaced neurons (gray matter), most often situated along the ventricular walls or within the subcortical white matter.
Leukoencephalopathy
MedGen UID:
78722
Concept ID:
C0270612
Disease or Syndrome
This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Cobblestone lissencephaly
MedGen UID:
96562
Concept ID:
C0431376
Congenital Abnormality
A form of lissencephaly characterized by an uneven cortical surface with a so called 'cobblestone' appearace. There are no distinguishable cortical layers.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
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.
Abnormal cerebral white matter morphology
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
An abnormality of the cerebral white matter.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Cerebellar vermis hypoplasia
MedGen UID:
333548
Concept ID:
C1840379
Finding
Underdevelopment of the vermis of cerebellum.
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Subcortical band heterotopia
MedGen UID:
336288
Concept ID:
C1848201
Disease or Syndrome
Subcortical band heterotopia is a condition in which nerve cells (neurons) do not move (migrate) to their proper locations in the fetal brain during early development. (Heterotopia means "out of place.") Normally, the neurons that make up the outer surface of the brain (cerebral cortex) are distributed in a well-organized and multi-layered way. In people with subcortical band heterotopia, some neurons that should be part of the cerebral cortex do not reach it. These neurons stop their migration process in areas of the brain where they are not supposed to be and form band-like clusters of tissue. Since these bands are located beneath the cerebral cortex, they are said to be subcortical. In most cases, the bands are symmetric, which means they occur in the same places on the right and left sides of the brain.\n\nThe abnormal brain development causes neurological problems in people with subcortical band heterotopia. The signs and symptoms of the condition depend on the size of the bands and the lack of development of the cerebral cortex. The signs and symptoms can vary from severe intellectual disability and seizures that begin early in life and affect both sides of the brain (generalized seizures) to normal intelligence with seizures occurring later in life and affecting only one side of the brain (focal seizures). Some affected individuals also have weak muscle tone (hypotonia), loss of fine motor skills such as using utensils, or behavioral problems. Subcortical band heterotopia is typically found when brain imaging is done following the onset of seizures, usually in adolescence or early adulthood.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Cerebellar hemisphere hypoplasia
MedGen UID:
867764
Concept ID:
C4022154
Anatomical Abnormality
Porencephalic cyst
MedGen UID:
906044
Concept ID:
C4082172
Disease or Syndrome
A cavity within the cerebral hemisphere, filled with cerebrospinal fluid, that communicates directly with the ventricular system.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Term Hierarchy

Follow this link to review classifications for Cobblestone lissencephaly without muscular or ocular involvement in Orphanet.

Professional guidelines

PubMed

Medina A
Surv Ophthalmol 2022 Mar-Apr;67(2):488-509. Epub 2021 Jun 25 doi: 10.1016/j.survophthal.2021.06.005. PMID: 34181975
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Ciofalo A, Gulotta G, Iannella G, Pasquariello B, Manno A, Angeletti D, Pace A, Greco A, Altissimi G, de Vincentiis M, Magliulo G
Curr Rheumatol Rev 2019;15(4):259-268. doi: 10.2174/1573397115666190227194014. PMID: 30827250

Recent clinical studies

Etiology

Nagpal R, Goyal RB, Priyadarshini K, Kashyap S, Sharma M, Sinha R, Sharma N
Indian J Ophthalmol 2022 Jul;70(7):2249-2261. doi: 10.4103/ijo.IJO_425_22. PMID: 35791104Free PMC Article
Lingam G, Sen AC, Lingam V, Bhende M, Padhi TR, Xinyi S
Eye (Lond) 2021 Aug;35(8):2086-2109. Epub 2021 Mar 21 doi: 10.1038/s41433-021-01501-5. PMID: 33746210Free PMC Article
Kontos AP, Deitrick JM, Collins MW, Mucha A
J Athl Train 2017 Mar;52(3):256-261. doi: 10.4085/1062-6050-51.11.05. PMID: 28387548Free PMC Article
Skef W, Hamilton MJ, Arayssi T
World J Gastroenterol 2015 Apr 7;21(13):3801-12. doi: 10.3748/wjg.v21.i13.3801. PMID: 25852265Free PMC Article
Liegl R, Ulbig MW
Ophthalmologica 2014;232(2):65-76. Epub 2014 Apr 26 doi: 10.1159/000360014. PMID: 24776999

Diagnosis

Bettiol A, Prisco D, Emmi G
Rheumatology (Oxford) 2020 May 1;59(Suppl 3):iii101-iii107. doi: 10.1093/rheumatology/kez626. PMID: 32348523
Llanos O, Hamzeh N
Med Clin North Am 2019 May;103(3):527-534. Epub 2019 Feb 21 doi: 10.1016/j.mcna.2018.12.011. PMID: 30955519
Salah S, Abad S, Monnet D, Brézin AP
J Fr Ophtalmol 2018 Dec;41(10):e451-e467. Epub 2018 Nov 16 doi: 10.1016/j.jfo.2018.10.002. PMID: 30449643
Pula JH, Yuen CA
Stroke Vasc Neurol 2017 Dec;2(4):210-220. Epub 2017 Jul 6 doi: 10.1136/svn-2017-000079. PMID: 29507782Free PMC Article
Nair AG, Patil-Chhablani P, Venkatramani DV, Gandhi RA
Indian J Ophthalmol 2014 Oct;62(10):985-91. doi: 10.4103/0301-4738.145987. PMID: 25449931Free PMC Article

Therapy

Liu SH, Saldanha IJ, Abraham AG, Rittiphairoj T, Hauswirth S, Gregory D, Ifantides C, Li T
Cochrane Database Syst Rev 2022 Oct 21;10(10):CD015070. doi: 10.1002/14651858.CD015070.pub2. PMID: 36269562Free PMC Article
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Cochrane Database Syst Rev 2019 Dec 18;12(12):CD011016. doi: 10.1002/14651858.CD011016.pub2. PMID: 31847055Free PMC Article
Cai S, Bressler NM
Curr Opin Ophthalmol 2017 Nov;28(6):636-643. doi: 10.1097/ICU.0000000000000424. PMID: 28837425
van Zuuren EJ, Fedorowicz Z, Carter B, van der Linden MM, Charland L
Cochrane Database Syst Rev 2015 Apr 28;2015(4):CD003262. doi: 10.1002/14651858.CD003262.pub5. PMID: 25919144Free PMC Article
Bielsa Marsol I
Actas Dermosifiliogr 2013 Oct;104(8):654-66. Epub 2013 Aug 13 doi: 10.1016/j.adengl.2012.10.012. PMID: 23948159

Prognosis

Costan VV, Bogdănici CM, Gheorghe L, Obadă O, Budacu C, Grigoraș C, Andronic DG, Niagu IA
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Bettiol A, Prisco D, Emmi G
Rheumatology (Oxford) 2020 May 1;59(Suppl 3):iii101-iii107. doi: 10.1093/rheumatology/kez626. PMID: 32348523
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Semin Ophthalmol 2020 Jan 2;35(1):7-26. Epub 2019 Dec 12 doi: 10.1080/08820538.2019.1687738. PMID: 31829761
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J Pediatr Ophthalmol Strabismus 2017 Sep 1;54(5):272-281. Epub 2017 Jul 31 doi: 10.3928/01913913-20170703-01. PMID: 28753216
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Crit Care 2015 Aug 5;19(1):274. doi: 10.1186/s13054-015-0993-7. PMID: 26242743Free PMC Article

Clinical prediction guides

Fernandez E, Phillips E, Saeed HN
Curr Opin Allergy Clin Immunol 2023 Oct 1;23(5):397-408. Epub 2023 Jul 26 doi: 10.1097/ACI.0000000000000932. PMID: 37493235
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Keene KR, Kan HE, van der Meeren S, Verbist BM, Tannemaat MR, Beenakker JM, Verschuuren JJGM
J Cachexia Sarcopenia Muscle 2022 Dec;13(6):2820-2834. Epub 2022 Sep 29 doi: 10.1002/jcsm.13089. PMID: 36172973Free PMC Article
Akhand O, Balcer LJ, Galetta SL
Curr Opin Neurol 2019 Feb;32(1):68-74. doi: 10.1097/WCO.0000000000000654. PMID: 30516648
Skef W, Hamilton MJ, Arayssi T
World J Gastroenterol 2015 Apr 7;21(13):3801-12. doi: 10.3748/wjg.v21.i13.3801. PMID: 25852265Free PMC Article

Recent systematic reviews

Bruschi G, Ghiglioni DG, Cozzi L, Osnaghi S, Viola F, Marchisio P
Clin Rev Allergy Immunol 2023 Aug;65(2):277-329. Epub 2023 Sep 2 doi: 10.1007/s12016-023-08970-4. PMID: 37658939Free PMC Article
Liu SH, Saldanha IJ, Abraham AG, Rittiphairoj T, Hauswirth S, Gregory D, Ifantides C, Li T
Cochrane Database Syst Rev 2022 Oct 21;10(10):CD015070. doi: 10.1002/14651858.CD015070.pub2. PMID: 36269562Free PMC Article
Dammacco R, Guerriero S, Alessio G, Dammacco F
Int Ophthalmol 2022 Feb;42(2):689-711. Epub 2021 Nov 21 doi: 10.1007/s10792-021-02058-8. PMID: 34802085Free PMC Article
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PLoS One 2020;15(12):e0242367. Epub 2020 Dec 15 doi: 10.1371/journal.pone.0242367. PMID: 33320867Free PMC Article
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J Am Acad Dermatol 2015 Feb;72(2):239-45. doi: 10.1016/j.jaad.2014.06.026. PMID: 25592340

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