Megalencephalic Leukoencephalopathy With Subcortical Cysts

Phenotype: MLC1

Gene: MLC1

Protein: membrane protein MLC1

Phenotype: MLC2A & MLC2B


Protein: hepatocyte cell adhesion molecule

Clinical Characteristics

MLC1/MLC2A: Classical Phenotype

  • Macrocephaly present at birth or within first year of life
  • Epileptic seizures
  • Normal to delayed early development, usually progressing to independent walking
  • Ataxia and spasticity in early childhood
  • Extrapyrimadal movement abnormalities
  • Mild intellectual deterioration in early teens
  • MRI findings:
    • Abnormal and swollen white matter, especially in cerebral hemisphere
    • Subcortical cysts in anterior temporal and frontoparietal regions

MLC2B: Improving Phenotype

  • Macrocephaly present at birth or within first year of life
  • Normal to delayed early development, progressing to independent walking
  • No regression of mental or motor function
  • Improved motor function after second or third year of life
  • Epileptic seizures may occur
  • Normal cognition to stable intellectual disability with or without autism
  • MRI findings:
    • Same abnormalities as MLC1 and MLC2A in the first year of life
    • Improvement seen on subsequent MRIs

Inheritance pattern:

  • Autosomal recessive for MLC1 and MLC2A
  • Autosomal dominant for MLC2B

What Can Be Learned From This Test

The diagnosis of MLC is based on diagnostic criteria, including brain MRI. A negative test result does not rule out a diagnosis of MLC since a mutation may not be identifiable with test methods used, or a mutation may be in another gene. This test will only detect mutations in MLC1 and HEPACAM.

Mutations in MLC1 and HEPACAM are found in 75 percent and 20 percent of affected individuals, respectively. Testing can be performed in tiers, moving to the next tier only if the preceding test is negative. Testing can also be performed concurrently, or in any order requested.

The following strategy is suggested:

  • Tier 1 sequencing of untranslated exon 1 and the entire coding region of MLC1
  • Tier 2 sequencing of the entire coding region of HEPACAM

This will detect point mutations, small deletions, and small insertions. It will not detect a partial or whole gene deletion or duplication. Sequencing will identify the majority of mutations, but partial gene deletions have been reported in MLC1 (Ilja Boor et al, 2006).

Sample Requirements

Draw 2ml–4ml of blood in EDTA/purple-top tube (minimum of 1ml–2ml for infants).

Turnaround time: 10-14 business days per tier

CPT Codes and Cost

Full Gene Sequencing

Tier 1

  • Code: 81479
  • Cost: $750

Tier 2

  • Code: 81479
  • Cost: $600

Known Variant Testing

  • Code: 81479
  • Cost: $225

Additional Information