• Test code: 03407
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Alternating Hemiplegia of Childhood Panel

Test description

The Invitae Alternating Hemiplegia of Childhood (AHC) Panel analyzes two genes that are associated with AHC, which is characterized by childhood onset of recurrent hemi- or quadriplegia, progressive cognitive decline and other variable neurological findings. These genes were selected based on the available evidence to date to provide Invitae’s broadest test for alternating hemiplegia of childhood.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.

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Primary panel (2 genes)
Add-on Clinically-overlapping Genes (3 genes)

AHC can clinically overlap with other disorders including familial hemiplegic migraine (FHM) and GLUT1 deficiency. In addition to the primary panel, clinicians can choose to include these clinically overlapping genes. FHM is characterized by migraine headaches with aura and affected individuals may also experience hemiparesis, seizures, ataxia, fever, visual and speaking difficulties, confusion, and loss of consciousness (PMID: 24498617, 18028456, 16437583, 18644608, 12953268, 16110494). Classic GLUT1 deficiency is characterized by infantile or childhood-onset treatment-resistant epilepsy, intellectual disability, microcephaly, complex movement disorders, and low cerebrospinal fluid glucose levels (PMID: 19304421). If clinically indicated, these gene can be added at no additional charge.


Alternative tests to consider

The Invitae Epilepsy Panel has been designed to provide a broad genetic analysis of epilepsy disorders. Depending on the individual’s clinical and family history, this broader panel may be appropriate.

  • alternating hemiplegia of childhood (AHC)
    • alternating hemiplegia of childhood 1
    • alternating hemiplegia of childhood 2

AHC is a rare neurological disorder that is characterized by infantile onset of episodic hemi- or quadriplegia that is typically accompanied by other neurological features. Onset of these episodes begin in infancy or early childhood (around 18 months of age) and episodes of hemiplegia can span from minutes to days in affected individuals.

In addition to hemiplegia, affected individuals may also experience dystonia, choreoathetoid movements, nystagmus, dyspnea and seizures. Developmental delay and progressive cognitive decline have been observed in almost all individuals with AHC.

Pathogenic variants in ATP1A3 account for the majority (~99%) of clinically diagnosed cases of AHC whereas pathogenic variants in ATP1A2 account for a small number of cases.

AHC is inherited in an autosomal dominant manner with most cases resulting from a de novo pathogenic variant.

Incomplete penetrance and variable expressivity, even within the same family, has been observed in cases of AHC.

AHC is estimated to affect 1:1,000,000 individuals.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ATP1A2 NM_000702.3
ATP1A3 NM_152296.4
CACNA1A* NM_001127221.1
SCN1A NM_001165963.1
SLC2A1 NM_006516.2

CACNA1A: Trinucleotide repeat expansions are not determined on this assay.