The Invitae KBG syndrome test analyzes the ANKRD11 gene that is associated with KBG syndrome. KBG syndrome is characterized by macrodontia of the central upper incisors, distinctive facial features, skeletal anomalies, seizures and intellectual disability.
Genetic testing of this gene 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.
KBG syndrome is characterized by macrodontia of the central upper incisors, distinctive facial dysmorphism, skeletal anomalies, short stature, seizures and intellectual disability. Characteristic facial features may include wide set eyes, telecanthus and brachycephaly. Common skeletal features in individuals with KBG syndrome include delayed bone age, vertebrae and rib anomalies, brachydactyly and clinodactyly. Less common features include cutaneous toe syndactyly, a webbed/short neck, cryptorchidism, hearing loss, palatal defects, strabismus and congenital heart defects.
ANKRD11 is the only gene known to be associated with KBG syndrome. However, due to the rarity of this condition, the percent of KBG syndrome attributed to pathogenic variants in ANKRD11 is currently unknown.
KBG syndrome is inherited in an autosomal dominant manner.
KBG syndrome is highly penetrant with clinical variability. Affected females sometimes exhibit a milder phenotype than affected males.
The prevalence of KBG syndrome is not clearly established but has been reported in approximately 60 individuals.
This test could be considered for patients who present with 4 or more of the following criteria (PMID: 17230487):
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|