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  • Test code: 04612
  • 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 Antley-Bixler syndrome Test

Test description

The Invitae Antley-Bixler Syndrome Test analyzes the POR gene that is associated with Antley-Bixler Syndrome (ABS), which is characterized by craniosynostosis with midface hypoplasia, radiohumeral synostosis, and joint contractures as well as genitourinary anomalies and impaired steroidogenesis.

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.

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Primary panel (1 gene)
Add-on Craniosynostosis Gene (1 gene)

Clinicians can also choose to include the FGFR2 single gene test. ABS demonstrates significant clinical overlap with craniosynostosis caused by mutations of the FGFR2 gene. Given the phenotypic similarity between these two conditions, analysis of the FGFR2 gene may be appropriate. This gene may be included at no additional charge.

FGFR2

Alternative tests to consider

Craniosynostosis is a feature of ABS as well as several other genetic syndromes. Given the significant overlap between ABS and other craniosynostosis syndromes, analyzing the genes associated with craniosynostosis may be appropriate. If clinically indicated, the Invitae Craniosynostosis Panel can be ordered in addition to this panel at no additional charge.

  • Antley-Bixler Syndrome
    • cytochrome P450 oxidoreductase (POR) deficiency
    • cortisol deficiency

POR deficiency is characterized by mild cortisol deficiency, adrenal crisis, ambiguous genitalia, primary amenorrhea, enlarged cystic ovaries, poor masculinization during puberty in males and maternal virilization during pregnancy with an affected fetus. Clinical features and severity are highly variable. Severely affected individuals present with classic ABS. ABS is characterized by congenital craniosynostosis, dysmorphic features, hydrocephalus, radiohumeral synostosis, joint contractures, renal anomalies and developmental delay. Individuals with moderate POR deficiency may have craniofacial and skeletal anomalies that are less severe than in ABS.

Due to the rarity of this condition, the percent of ABS attributed to pathogenic variants in POR is currently unknown.

ABS is inherited in an autosomal recessive manner.

ABS is highly penetrant with clinical variability.

The prevalence of ABS is not clearly established but has been reported in approximately 60 individuals.

The main characteristics of a patient for whom this test would be appropriate for include:

  • craniosynostosis
  • brachycephaly
  • severe midface hypoplasia
  • radiohumeral synostosis
  • multiple joint contractures
  • ambiguous genitalia
  • impaired steroidogenesis

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
FGFR2 NM_000141.4
POR NM_000941.2