The Invitae Trichorhinophalangeal Syndrome Panel analyzes two genes that are associated with trichorhinophalangeal syndrome (TRPS), which is characterized by short stature, cone-shaped epiphyses, brachydactyly, sparse hair and a bulbous nasal tip, and variable exostoses and intellectual deficit. Contiguous deletions of the TRPS1 and EXT1 genes cause TRPS type 2, also known as Langer-Giedion syndrome, which is characterized by multiple osteochondromas and distinctive facial and skeletal features.
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.
EXT1 EXT1 TRPS1
EXT1 EXT1 TRPS1
TRPS is a skeletal dysplasia characterized by a distinctive facial appearance, skeletal abnormalities, and short stature. Patients have sparse, slowly growing scalp hair, laterally sparse eyebrows, a bulbous tip of the nose, protruding ears, long flat philtrum and thin upper vermillion border. The most typical radiographic findings in TRPS are cone-shaped epiphyses, predominantly at the middle phalanges, which are often not detectable before 2 years of age. Hip malformations such as coxa plana, coxa magna, or coxa vara are present in >70% of patients. Patients with the milder form of the syndrome are sometimes described as having TRPS type I, whereas patients with more severe presentation (shorter stature and very short fingers, known as brachydactyly) are sometimes described as having TRPS type III. TRPS type II, also called Langer-Giedion syndrome, can be distinguished from types I and III on the basis of intellectual deficit and the presence of exostoses.
Pathogenic variants in TRPS1 are responsible for 86% of TRPS types I and III. Contiguous gene deletions including TRPS1 and EXT1 are the only known genetic causes of TRPS type II.
This condition is inherited in an autosomal dominant manner, although several sporadic cases of TRPS type II have been reported.
TRPS is highly penetrant with variable expressivity.
The prevalence is not clearly established, but TRPS type II is very rare while TRPS types I and III have been reported in over 100 individuals.
The main characteristics of a patient for whom this test would be appropriate for include:
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|