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  • Test code: 04614
  • 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
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Invitae Hereditary Multiple Osteochondromas Panel

Test description

The Invitae Hereditary Multiple Osteochondromas Panel analyzes up to 3 genes that are associated with hereditary multiple osteochondromas (HMO), which is characterized by multiple cartilage-capped bone growths (known as osteochondromas or osteocartilaginous exostoses) arising from the growth plate area in the juxta-epiphyseal region of long tubular bones or from the surface of flat bones.

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 (4 genes)
Add-on Langer-Giedion Syndrome Gene (1 gene)

Contiguous deletions of the TRPS1 and EXT1 genes cause Langer-Giedion syndrome, which is characterized by multiple osteochondromas and distinctive facial and skeletal features. In individuals with multiple osteochondromas and additional distinctive facial features such as sparse, slowly growing scalp hair, laterally sparse eyebrows, a bulbous tip of the nose, protruding ears, long flat philtrum and thin upper vermillion border, analysis of the TRPS1 gene may be considered. This gene can be added at no additional charge.

TRPS1

  • hereditary multiple osteochondromas (HMO)

HMO is a skeletal disease characterized by multiple cartilage-capped bone growths, known as osteochondromas or osteocartilaginous exostoses, arising from the growth plate area in the juxta-epiphyseal region of long tubular bones or from the surface of flat bones. Most lesions appear in children and adolescents as painless, slow-growing masses, which increase in size and number until the growth plates close when skeletal maturation is achieved at the end of puberty. There is significant inter- and intrafamilial phenotypic variability, including variation in the number and size of osteochondromas, the number and location of involved bones, and the degree of deformities. These tumors mainly occur on the distal femur (90%), and the proximal tibia (84%), fibula (76%), and humerus (72%). Although osteochondromas are benign tumors, they may cause secondary complications including fracture, bony deformity, mechanical joint problems, and compression of nerves, tendons, and blood vessels. Osteochondromas are often accompanied by short stature. The most serious complication is the malignant transformation of an osteochondroma toward a secondary peripheral chondrosarcoma, occurring in 1–5% of patients, the risk of which increases with age.

Full gene sequencing and duplication/deletion analysis are expected to identify pathogenic variants in 85 to 95 percent of affected individuals.

HMO is inherited in an autosomal dominant manner, although de novo variants have been reported.

HMO is highly penetrant with variable expressivity.

The prevalence of HMO has been estimated in general populations between 1 in 50,000 and 1 in 100,000. In a small population in Guam, the prevalence has been estimated at 1 in 100.

Analysis of the EXT1 and EXT2 genes may be appropriate for any individual with multiple osteochondromas, with or without a family history of the same.

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 in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

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
EXT1 NM_000127.2
EXT1 NM_000127.2
EXT2 NM_207122.1
EXT2 NM_207122.1
TRPS1 NM_014112.4