The Invitae Baraitser-Winter Cerebrofrontofacial Syndrome Panel analyzes two genes that are associated with Baraitser-Winter cerebrofrontofacial (BWCFF) syndrome, which is characterized by variable brain anomalies ranging from pachygyria through lissencephaly and accompanied by facial features, short stature, congenital heart defects, hearing loss, genitourinary problems, and muscle wasting. Additional features, such as seizures, renal anomalies, and congenital heart defects are also common. These genes were selected based on the available evidence to date to provide Invitae’s broadest test for BWCFF syndrome.
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.
The features exhibited in BWCFF syndrome are similar to and overlap with those present in RASopathies (such as Noonan syndrome). This panel can be ordered with this test at no additional charge.
The features exhibited in BWCFF syndrome are similar to and overlap with those present in Kabuki syndrome. This panel can be ordered with this test at no additional charge.
BWCFF syndrome is a heterogeneous syndrome that can present across a spectrum from mild to profound developmental delay and intellectual disability, facial features, coloboma and additional symptoms. The severity of intellectual disability/developmental delay and presence of seizures correlates with the degree to which neuronal migration defects are evident. The most frequent observation is pachygyria; however, some individuals show no obvious defect, while others manifest lissencephaly.
Common facial features include hypoplasia, coloboma of the retina or iris, hypertelorism, ptosis, high-arched brows, broad nasal bridge, long philtrum and pointed chin. Other common features include sensorineural hearing loss, muscle wasting, congenital heart defects and short stature. Additionally, genitourinary/renal problems and contractures have been reported. Expressivity is noted to be highly variable.
Variants in ACTB appear to represent >60% of disease while variants in ACTG1 probably represents about 20%. It is not known if other genes may also cause this disease.
This condition is inherited in an autosomal dominant manner and, to date, most reported variants have been de novo.
This condition is believed to be fully penetrant.
This condition is very rare, with only about 50 individuals confirmed with a diagnosis to date. However, it is thought that this condition is under-recognized, and therefore, the actual prevalence may be significantly higher.
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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|