Invitae Small Fiber Neuropathy Test


Test description

The Invitae Small Fiber Neuropathy Test analyzes up to two genes that are associated with small fiber neuropathy (SFNP), a type of peripheral neuropathy characterized by severe pain episodes that typically begin in the hands or feet, then affect larger areas of the body over time. Nerve biopsies typically show reduced intraepidermal nerve fiber density (IENFD) affecting small-diameter nerve fibers. The genes in this test were curated based on current available evidence to provide a comprehensive test for the genetic causes of SFNP.

Given that small fiber neuropathy is a heterogeneous disorder, identification of the underlying genetic cause can help predict patient outcome and inform recurrence risk.

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Primary panel (1 gene)


Add-on preliminary-evidence gene (1 gene)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future. This gene can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


Congenital indifference to pain (CIP), familial episodic pain syndrome (FEPS), generalized epilepsy with febrile seizures plus (GEFS+), hereditary sensory and autonomic neuropathy (HSAN), paroxysmal extreme pain disorder (PEXPD), primary erythermalgia (PE), small fiber neuropathy (SFNP)

Small fiber neuropathy (SFNP) is characterized by neuropathic burning or stabbing pain that typically occurs in the distal lower extremities and presents between adolescence and adulthood. Pain may be accompanied by autonomic symptoms such as heart palpitations, dry eyes, dry mouth, heart palpitations, and/or orthostatic hypotension-induced dizziness. Affected individuals typically experience heightened sensitivity to pain in general, but cannot feel pain concentrated in very small areas, such as a pinprick. Individuals may also have other sensory issues, such as the reduced ability to differentiate between hot and cold temperatures. Symptoms of this painful neuropathy may worsen over time and extend to include other parts of the body in addition to the hands and feet. The principal nerve biopsy finding consists of decreased small nerve fiber diameter.

Gene Inheritance Clinical subtypes and other conditions associated with each gene
Autosomal dominant Autosomal recessive X-linked
SCN9A generalized epilepsy with febrile seizures plus (GEFSP), primary erythermalgia, hereditary sensory and autonomic neuropathy type 2D (HSAN2D), congenital insensitivity to pain (CIP), paroxysmal extreme pain disorder (PEXPD)
SCN10A familial episodic pain syndrome 2 (FEPS2)

Pathogenic variants in the SCN9A gene account for approximately 30% of cases of small fiber neuropathy. The proportion of small fiber neuropathy accounted for by SCN10A is unknown.

SFNP associated with the SCN9A and SCN10A genes is inherited in an autosomal dominant pattern. The SCN9A gene is also associated with disorders inherited in an autosomal recessive pattern.

SFNP is a rare disorder whose overall prevalence is unknown. One study estimated the overall minimum prevalence at 52 per 100,000 individuals.

The clinical spectrum of small fiber neuropathies is broad. Genetic testing may confirm a suspected diagnosis or rule out disorders with similar symptoms. A genetic diagnosis may also help predict disease progression and inform recurrence risk.

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, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
SCN10A NM_006514.3
SCN9A NM_002977.3