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Cobblestone lissencephaly without muscular or ocular involvement(LIS5)

MedGen UID:
Concept ID:
Disease or Syndrome
Synonym: Lissencephaly 5
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
Concept ID:
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


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:
Concept ID:
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Occipital encephalocele
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Concept ID:
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.
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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.
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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:
Concept ID:
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Gray matter heterotopia
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Concept ID:
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.
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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
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Concept ID:
Congenital Abnormality
Underdevelopment of the corpus callosum.
Cobblestone lissencephaly
MedGen UID:
Concept ID:
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:
Concept ID:
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:
Concept ID:
Pathologic Function
An abnormality of the cerebral white matter.
Severe global developmental delay
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Concept ID:
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Cerebellar vermis hypoplasia
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Concept ID:
Underdevelopment of the vermis of cerebellum.
Hypoplasia of the brainstem
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Concept ID:
Underdevelopment of the brainstem.
Subcortical band heterotopia
MedGen UID:
Concept ID:
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:
Concept ID:
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
Concept ID:
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:
Concept ID:
Anatomical Abnormality
Porencephalic cyst
MedGen UID:
Concept ID:
Disease or Syndrome
A cavity within the cerebral hemisphere, filled with cerebrospinal fluid, that communicates directly with the ventricular system.
MedGen UID:
Concept ID:
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.
MedGen UID:
Concept ID:
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:
Concept ID:
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.
MedGen UID:
Concept ID:
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


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Recent clinical studies


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Clinical prediction guides

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Recent systematic reviews

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