Stickler Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10271 BMP4 81479,81479 Order Options and Pricing
COL11A1 81479,81479
COL11A2 81479,81479
COL2A1 81479,81479
COL9A1 81479,81479
COL9A2 81479,81479
COL9A3 81479,81479
GZF1 81479,81479
LOXL3 81479,81479
LRP2 81479,81479
PLOD3 81479,81479
VCAN 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10271Genes x (12)81479 81479 $960 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

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

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Stickler syndrome (STL) is a multisystem disorder characterized by ocular, skeletal, orofacial and auditory defects with an estimated prevalence of 1:7,500-1:9,000 (Robin et al. 2017. PubMed ID: 20301479). Ocular defects include myopia, cataract, and retinal detachment. Hearing loss can be both conductive and sensorineural. Other features include midfacial underdevelopment and cleft palate and mild spondyloepiphyseal dysplasia and/or precocious arthritis (Robin et al. 2017. PubMed ID: 20301479).

Stickler syndrome Type I (STL1) is characterized by “membranous” congenital vitreous anomaly; Stickler syndrome Type II (STL2) is characterized by “beaded” congenital vitreous anomaly, Stickler syndrome (STL3) has craniofacial and joint abnormalities and hearing loss, but no ocular findings. Stickler syndrome Type IV and Type V have moderate-to-severe sensorineural hearing loss and moderate-to-high myopia with vitreoretinopathy (Baker et al. 2011. PubMed ID: 21671392). Stickler syndrome Type VI features moderate-to-severe sensorineural hearing loss, moderate-to-high myopia, and midface retrusion (Faletra et al. 2014. PubMed ID: 24273071). One study suggested that hearing loss (mostly mild to moderate) was found in ~60% of Stickler patients (Acke et al. 2012. PubMed ID: 23110709). Stickler syndrome was also found in 39 out of 141 newborns who were diagnosed with Pierre-Robin sequence (Thouvenin et al. 2013. PubMed ID: 23303695).

Other skeletal disorders have overlapping clinical features with Stickler syndrome, which cause difficulties in reaching a correct clinical diagnosis. Molecular diagnosis of the skeletal dysplasia subtypes is also complex because extensive genetic heterogeneity exists for each disorder (Warman et al. 2011. PubMed ID: 21438135; Mortier et al. 2019. PubMed ID: 31633310). Considering the clinical and genetic heterogeneity, a molecular testing approach that interrogates all known Stickler syndrome genes is highly recommended.

Genetics

The inheritance patterns of Stickler syndrome can be autosomal dominant (AD) or autosomal recessive (AR) (Robin et al. 2017. PubMed ID: 20301479). COL2A1COL11A1, and COL11A2 are the major genes associated with autosomal dominant Stickler syndrome, while COL9A1COL9A2 and COL9A3 are responsible for autosomal recessive Stickler syndrome (Robin et al. 2017. PubMed ID: 20301479; Van Camp et al. 2006. PubMed ID: 16909383; Baker et al. 2011. PubMed ID: 21671392; Nikopoulos et al. 2011. PubMed ID: 21421862; Vijzelaar et al. 2013. PubMed ID: 23621912). The proportion of de novo causative variants in Sticker syndrome patients is currently unknown (Robin et al. 2017. PubMed ID: 20301479).

Only a few LOXL3 variants were reported in individuals with autosomal recessive Stickler syndrome (Alzahrani et al. 2015. PubMed ID: 25663169; Chan et al. 2019. PubMed ID: 30362103).

Pathogenic variants in LRP2 mainly cause Donnai–Barrow syndrome (DBS) (Longoni et al. 2018. PubMed ID: 20301732). Recently, an undocumented homozygous LRP2 variant was found in two sibs, from one Saudi consanguineous family, affected with a predominant eye phenotype similar to Stickler syndrome (Schrauwen et al. 2014. PubMed ID: 23992033). To date, only a few autosomal recessive Stickler syndrome cases have been reported.

Pathogenic variants in VCAN cause Wagner syndrome (WS) (Kloeckener-Gruissem. 2016. PubMed ID: 20301747). The overlapping clinical features in WS and Stickler syndrome are myopia, presenile cataract, vitreous degeneration, radial perivascular retinal degeneration, and tractional retinal detachments (Kloeckener-Gruissem. 2016. PubMed ID: 20301747).

Several variants in BMP4 were reported in patients with cleft lip/palate (Suzuki. 2009. PubMed ID: 19249007). One truncating variant was reported to segregate in a family with autosomal dominant Stickler syndrome and renal dysplasia (Nixon et al. 2019. PubMed ID: 30568244). Approximately 10 large deletion/duplications involving BMP4 were reported in patients with eye, brain, and limb defects, and other conditions (Human Gene Mutation Database).

To date, only two homozygous variants in GZF1 were found in two consanguineous families with Larsen Syndrome (Patel et al. 2017. PubMed ID: 28475863). Larsen syndrome overlaps several features with Stickler syndrome such as severe myopia and hearing loss.

Only a few variants in PLOD3 were reported in patients with autosomal recessive connective tissue disorder (Ewans et al. 2019. PubMed ID: 31129566).

See individual gene test descriptions for information on molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Causative variants in COL2A1 and COL11A1 account for 80-90% and 10-20% of variants identified in autosomal dominant STL syndrome, respectively; causative variants in COL11A2 account for rare dominant cases. Causative variants in  COL2A1COL9A1COL9A2, COL9A3, LOXL3 and LRP2 have been found only in a few families affected with autosomal recessive inheritance of STL syndrome (Robin et al. 2017. PubMed ID: 20301479; Schrauwen et al. 2014. PubMed ID: 23992033; Alzahrani et al. 2015. PubMed ID: 25663169; Tham et al. 2015. PubMed ID: 25060605). Causative variants in VCAN were identified in ten out of twelve families diagnosed with VCAN-related vitreoretinopathy (Kloeckener-Gruissem. 2016. PubMed ID: 20301747). Only one BMP4 truncating variant was reported to segregate in a family with autosomal dominant Stickler syndrome and renal dysplasia (Nixon et al. 2019. PubMed ID: 30568244).

The sensitivity for large deletions and duplications in COL2A1COL11A2COL9A1, COL9A2, and COL9A3 is probably low, because only a few cases with large deletions and insertions involving these five genes have been reported (van der Hout et al. 2002. PubMed ID: 12204008; Human Mutation Database). However, large deletions in COL11A1 were detected in six unrelated Stickler syndrome patients by MLPA methods (Vijzelaar et al. 2013. PubMed ID: 23621912).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with clinical and radiologic features consistent with Stickler syndrome and related disorders. This test especially aids in a differential diagnosis of similar phenotypes, rules out particular syndromes, and provides the analysis of multiple genes simultaneously. Individuals who are suspected of any of these disorders, especially if clinical diagnosis is unclear, and individuals who have been found to be negative by mutation analysis for single gene tests are candidates.

Genes

Official Gene Symbol OMIM ID
BMP4 112262
COL11A1 120280
COL11A2 120290
COL2A1 120140
COL9A1 120210
COL9A2 120260
COL9A3 120270
GZF1 613842
LOXL3 607163
LRP2 600073
PLOD3 603066
VCAN 118661
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Acke et al. 2012. PubMed ID: 23110709
  • Alzahrani et al. 2015. PubMed ID: 25663169
  • Baker et al. 2011. PubMed ID: 21671392
  • Chan et al. 2019. PubMed ID: 30362103
  • Ewans et al. 2019. PubMed ID: 31129566
  • Faletra et al. 2014. PubMed ID: 24273071
  • Human Gene Mutation Database (Biobase).
  • Kloeckener-Gruissem. 2016. PubMed ID: 20301747
  • Longoni et al. 2018. PubMed ID: 20301732
  • Mortier et al. 2019. PubMed ID: 31633310
  • Nikopoulos et al. 2011. PubMed ID: 21421862
  • Nixon et al. 2019. PubMed ID: 30568244
  • Patel et al. 2017. PubMed ID: 28475863
  • Robin et al. 2017. PubMed ID: 20301479
  • Schrauwen et al. 2014. PubMed ID: 23992033
  • Suzuki. 2009. PubMed ID: 19249007
  • Tham et al. 2015. PubMed ID: 25060605
  • Thouvenin et al. 2013. PubMed ID: 23303695
  • Van Camp et al. 2006. PubMed ID: 16909383
  • Van Der Hout et al. 2002. PubMed ID: 12204008
  • Vijzelaar et al. 2013. PubMed ID: 23621912
  • Warman et al. 2011. PubMed ID: 21438135

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.

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


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.

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