Invitae Alpha Thalassemia X-linked Intellectual Disability Test


Test description

This test analyzes the ATRX gene, which is associated with alpha thalassemia X-linked intellectual disability syndrome (ATRX). ATRX is characterized by distinctive facial features, severe developmental delays, genital anomalies, intellectual disability, and abnormal hemoglobin H production.

Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.

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Primary panel (1 gene)


Alpha thalassemia X-linked intellectual disability syndrome (ATRX)

ATRX is a rare form of intellectual disability that is characterized by distinctive facial features including telecanthus, short nose, tented vermilion of the upper lip, and thick or everted vermilion of the lower lip with coarsening of the facial features over time. Genital anomalies including hypospadias and undescended testes, ambiguous genitalia, and normal external female genitalia in a 46,XY individual have also been reported. Skeletal findings include short stature, brachydactyly, tapering fingers, clinodactyly, digital contractures, overlapping digits, pes planus, varus and valgus foot deformations, pectus carinatum, kyphosis, scoliosis, and dimpling over the lower spine. Additionally profound developmental delay is a common feature. Although anemia manifestations characteristic of alpha-thalassemia may be observed, many individuals with ATRX syndrome have normal hematological findings and show no signs of thalassemia.

ATRX is the only known gene associated with alpha thalassemia X-linked intellectual disability syndrome.

ATRX is inherited in an X-linked pattern.

All males with a pathogenic variant in ATRX have been reported to be affected. Females with a pathogenic variant are typically asymptomatic carriers, though rare cases of females affected due to skewed X-inactivation have been reported.

There have been roughly 200 reported cases, but the exact prevalence remains unknown.

Testing for ATRX should be considered in individuals with a personal history of:

  • characteristic craniofacial features
  • microcephaly
  • genital anomalies
  • skeletal anomalies
  • laboratory findings of alpha-thalassemia
  • intellectual disability, typically in the severe to profound range

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, 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
ATRX NM_000489.4