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Megalencephalic Leukoencephalopathy with Subcortical Cysts via the HEPACAM Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7695 HEPACAM 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7695HEPACAM81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Renee Bend, PhD

Clinical Features and Genetics

Clinical Features

Megalencephalic leukoencephalopathy with subcortical cysts (MLC, OMIM 604004), also known as Van der Knaap disease, is a slowly progressive myelinopathy characterized by macrocephaly, delay in walking, early-onset ataxia, seizure, and spasticity. Motor dysfunction, mild mental retardation, and behavioral problems may occur later in life. Additional late-onset symptoms include cerebellar ataxia, hypertonia, dysarthria, and dysphagia. Hallmark magnetic resonance imaging (MRI) findings include subcortical cysts in the tips of the temporal lobes and in frontoparietal subcortical areas and swollen cerebral white matter. Onset of symptoms usually occurs during the first year of life (Van der Knaap et al. Ann Neurol 37:324-334, 1995). MLC is clinically heterogeneous with regards to age of onset, degree of macrocephaly and mental impairment, severity, and disease progression. MLC is a rare disease that affects patients worldwide. Incidence is higher than expected within consanguineous populations (Topcu et al. Brain Dev 20:142-153, 1998).

Genetics

Defects in two genes, MLC1 and HEPACAM, have been reported in patients with MLC (Leegwater et al. Am J Hum Genet 68:831-838, 2001; López-Hernández et al. Am J Hum Genet 88:422-32, 2011). About 75% of MLC patients have variants in the MLC1 gene. In these patients, the disease is inherited with an autosomal recessive pattern. Variants in the HEPCAM gene have been reported in the majority of patients without MLC1 variants. In about 45% of these patients, the clinical symptoms and MRI findings recover significantly over time, while the macrocephaly is maintained. In this group, patients have only one heterozygous HEPACAM variant, and the parents with the variants have macrocephaly, indicating a dominant mode of inheritance. About 25% of the patients without MLC1 variants have the typical MLC phenotype. This group of patients have two recessive HEPACAM variants, while their asymptomatic parents are heterozygous for the variants, indicating a recessive mode of inheritance. To date, fifteen different pathogenic HEPACAM variants, mostly missense, have been reported. The HEPACAM gene encodes GlialCAM, an IgG-like cell adhesion molecule that binds directly to the MLC1 protein (López-Hernández et al. 2011).

Clinical Sensitivity - Sequencing with CNV PG-Select

This test detects variants in ~ 75% of individuals with MLC, who do not have MLC1 variants.

Testing Strategy

This test provides full coverage of all coding exons of the HEPACAM gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with clinical diagnosis and MRI findings of MLC, without MLC1 variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in HEPACAM.

Gene

Official Gene Symbol OMIM ID
HEPACAM 611642
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Megalencephalic Leukoencephalopathy with Subcortical Cysts Panel

Citations

  • Leegwater, P. A., et.al. (2001). "Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts." Am J Hum Genet 68(4): 831-8. PubMed ID: 11254442
  • Lopez-Hernandez, T., et.al. (2011). "Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism." Am J Hum Genet 88(4): 422-32. PubMed ID: 21419380
  • Topcu, M., et.al. (1998). "Megalencephaly and leukodystrophy with mild clinical course: a report on 12 new cases." Brain Dev 20(3): 142-53. PubMed ID: 9628190
  • van der Knaap, M. S., et.al. (1995). "Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children." Ann Neurol 37(3): 324-34. PubMed ID: 7695231

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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