The Invitae Rubinstein-Taybi syndrome test analyzes two genes associated with Rubinstein-Taybi syndrome (RSTS), a multisystem disorder characterized by short stature, recognizable facial features, broad thumbs and great toes, and moderate to severe intellectual disability.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.
Rubinstein-Taybi syndrome is characterized by distinctive facial features, broad thumbs, broad great toes, short stature, and intellectual disability. Other associated features include postnatal growth deficiency, obesity in later childhood/adolescence, ophthalmologic anomalies, congenital heart defects, genitourinary anomalies including cryptorchidism in males, and keloid formation. An increased tumor risk has been recognized in Rubinstein-Taybi syndrome.
Approximately 50-60% of patients with a strong clinical suspicion of RSTS have a pathogenic variant in CREBBP and 3-8% of patients have a pathogenic variant in EP300.
Rubinstein-Taybi syndrome is inherited in an autosomal dominant manner. Many cases occur de novo, although parent-to-child transmissions and somatic mosaicism have been reported.
RSTS is highly penetrant with variable expressivity.
Rubinstein-Taybi syndrome has a prevalence of approximately 1 in 100,000 to 125,000.
This test could be considered for patients who present with intellectual disability, obesity, short stature, broad thumbs and toes, and characteristic facial features including downslanting palpebral fissures, arched brows and grimacing smile. Other clinical features include congenital heart defects, renal abnormalities, cryptorchidism and eye abnormalities.
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|