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Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability(MLC2B)

MedGen UID:
Concept ID:
Disease or Syndrome
Gene (location): HEPACAM (11q24.2)
Monarch Initiative: MONDO:0013491
OMIM®: 613926

Disease characteristics

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is characterized by two phenotypes: classic MLC and improving MLC. Individuals with classic MLC present with macrocephaly, often in association with seizures, gradual onset of ataxia, spasticity, and sometimes extrapyramidal findings, mild gross motor developmental delays, and late-onset cognitive deterioration. Macrocephaly, observed in most affected individuals, may be present at birth but more frequently develops during the first year of life. The degree of macrocephaly is variable, with head circumferences reaching four to six standard deviations greater than the mean. After the first year of life, head growth trajectory typically normalizes and growth follows a line parallel to, although several standard deviations above, the 98th centile. Initial mental and motor development is normal in most individuals. Walking is often unstable, followed by ataxia of the trunk and extremities, pyramidal dysfunction, and brisk deep tendon reflexes. Early-onset seizures are common, and approximately 60% of individuals have epilepsy that is typically well controlled with anti-seizure medication, but status epilepticus occurs relatively frequently. Cognitive deterioration occurs later in the course of the disease and is usually mild in severity. Overall disease severity varies, with some individuals being able to ambulate independently for only a few years from disease onset to other individuals continuing to independently walk in the fifth decade of life. Individuals with improving MLC have a similar initial presentation with delayed cognitive or motor development, followed by an improving clinical course: macrocephaly usually persists, but some children become normocephalic; motor function improves or normalizes; hypotonia and clumsiness may persist in some or neurologic examination may become normal. Some individuals have intellectual disability that is stable, with or without autism spectrum disorder. Epilepsy is much less frequent than in classic MLC. [from GeneReviews]
Rogier Min  |  Truus EM Abbink  |  Marjo S van der Knaap   view full author information

Additional description

Autosomal dominant remitting megalencephalic leukoencephalopathy with subcortical cysts-2B (MLC2B) is characterized by infantile-onset of macrocephaly and mildly delayed motor development associated with white matter abnormalities on brain MRI that improve with age. As children, some patients have mild residual hypotonia or clumsiness, but otherwise have no residual motor abnormalities. About 40% of patients have impaired intellectual development (summary by van der Knaap et al., 2010 and Lopez-Hernandez et al., 2011). For a discussion of genetic heterogeneity of megalencephalic leukoencephalopathy with subcortical cysts, see MLC1 (604004).  http://www.omim.org/entry/613926

Clinical features

From HPO
MedGen UID:
Concept ID:
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.
MedGen UID:
Concept ID:
Congenital Abnormality
Diffuse enlargement of the entire cerebral hemispheres leading to macrocephaly (with or without overlying cortical dysplasia).
MedGen UID:
Concept ID:
Sign or Symptom
Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects.
Delayed speech and language development
MedGen UID:
Concept ID:
A degree of language development that is significantly below the norm for a child of a specified age.
Motor delay
MedGen UID:
Concept ID:
A type of Developmental delay characterized by a delay in acquiring motor skills.
Absent speech
MedGen UID:
Concept ID:
Complete lack of development of speech and language abilities.
Diffuse swelling of cerebral white matter
MedGen UID:
Concept ID:
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.
Diffuse white matter abnormalities
MedGen UID:
Concept ID:
Anatomical Abnormality
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines


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Clinical prediction guides

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