Invitae Senior-Loken Syndrome Panel


Test description

The Invitae Senior-Loken Syndrome Panel analyzes four genes that are associated with Senior-Loken syndrome (SLSN). These genes are involved in the structure of cilia. Cilia are necessary for proper cellular motility, for the movement of material around a cell, and for chemical signaling pathways. Mutations in any of these genes impact the structure and function of cilia and likely disrupt signaling pathways.

Individuals inheriting heterozygous gene changes are at risk of developing visual impairment (including blindness) and end stage renal disease by the end of the second decade of life. The visual complications cannot be prevented, but the renal disease is often insidious and may not be diagnosed until quite advanced. Early identification of SLSN can allow for proper renal surveillance and management.

Order test

Primary panel (4 genes)


CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.

Alternative tests to consider

Senior-Loken syndrome is a member of a class of disorders called ciliopathies. Ciliopathies are caused by pathogenic variants in genes that affect the function of cilia—the hair-like structures on the surface of cells. Ciliopathies share many overlapping symptoms, often making it difficult to distinguish between them based on clinical presentation alone.

The Invitae Sensory Ciliopathies Panel has been designed to provide a broad genetic analysis of this class of disorders and may be considered as an alternative to testing for a specific disorder. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional charge.

Senior-Loken syndrome (SLSN)

Senior-Loken syndrome (SLSN) is a rare pediatric oculorenal disease characterized by the association of nephronophthisis (NPHP) and retinal dystrophy. It is often considered to be a Joubert syndrome related disease (JSRD) because many individuals originally diagnosed with SLSN were found to have additional clinical features that were reminiscent of JSRD, including molar tooth sign and developmental delay.

SLSN usually presents within the first two decades of life. Retinal lesions are variable, ranging from severe Leber congenital amaurosis (LCA), which can cause blindness in early infancy, to later onset retinitis pigmentosa (RP). Other ocular symptoms can include cataract, Coat’s disease, and keratoconus. Renal disease often manifests as a medullary cystic kidney disease known as nephronophthisis, whose symptoms are identical to those of isolated nephronophthisis (NPHP)—polyuria, polydipsia, and impaired ability to concentrate urine. Onset of renal disease can be insidious, with a severe progression to end stage renal disease by 13 years of age. Occasionally, neurologic features that are typical of classic Joubert syndrome are present, including molar tooth sign, ataxia, hypotonia, developmental delay, nystagmus, and abnormal breathing patterns.

The precise clinical sensitivity of this panel test is unknown due to the rarity of SLSN, but it is expected to exceed 30% for individuals with both nephronopthisis and retinal dystrophy.

SLSN is inherited in an autosomal recessive pattern.

There is phenotypic variability in the onset and severity of the retinal disease. End stage renal disease appears to be fully penetrant.

The prevalence of SLSN worldwide is estimated at 1 in 1,000,000 worldwide, but prevalence of the Joubert syndrome and related disorders (JSRD) has been estimated at 1 in 80,000 to 1 in 100,000. This may be an underestimate; the figures will continue to evolve as the genetic etiology of JSRD is elucidated.

Testing for SLSN should be considered in any individual presenting with visual impairment and renal failure within the first two decades of life. Additionally, any infant presenting with Leber congenital amaurosis should be tested for SLSN in order to rule out the risk of childhood renal failure.

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
CEP290* NM_025114.3
IQCB1 NM_001023570.2
NPHP1 NM_000272.3
NPHP4 NM_015102.4

CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.