• Test code: 04214
  • 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

Invitae Sotos Syndrome Test

Test description

The Invitae Sotos Syndrome test analyzes NSD1, which is associated with Sotos syndrome. Sotos syndrome belongs to a group of overgrowth disorders that can be difficult to distinguish clinically. Genetic testing may provide a concrete and accurate diagnosis in these cases. Identifying a genetic cause of symptoms that may be related to Sotos syndrome can guide an individual’s medical management, provide a predicted outcome, and indicate the recurrence risk.

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Primary panel (1 gene)
  • Sotos syndrome

Sotos syndrome is an overgrowth disorder that is characterized by distinct facial features, excessive growth during childhood, macrocephaly, and mild-to-severe learning disability. Characteristic facial features include high forehead, long face, reddened cheeks, small pointed chin, and down-slanting palpebral fissures.

Sotos syndrome is usually identified in the neonatal period by excessive height, advanced bone age, hypotonia and feeding difficulties, and the characteristic facial appearance. Some individuals with Sotos syndrome may also have scoliosis, congenital heart defects, seizures, neonatal jaundice, and behavioral problems such as aggression and autism spectrum disorder. Sotos syndrome can also be associated with an increased risk of tumor development.

NSD1 is the only gene known to be associated with Sotos syndrome. Approximately 80%-90% of people with Sotos syndrome have a detectable change in NSD1. Among those with classic Sotos syndrome, approximately 50% of individuals of Japanese heritage and 10% of individuals of non-Japanese heritage have a 5q35 microdeletion that encompasses the entire NSD1 gene. Individuals with a 5q35 microdeletion have less childhood overgrowth and more severe learning disability than individuals with an intragenic mutation.

Sotos syndrome is inherited in an autosomal dominant pattern.

Sotos syndrome is considered fully penetrant; it is expected that all individuals with a change in NSD1 gene causing Sotos syndrome will show at least some features at birth. Sotos syndrome shows highly variable expressivity. Individuals in the same family with the same NSD1 variant can present with different features.

The incidence of Sotos syndrome is approximately 1:10,000-1:14,000 live births. Incidence may be higher: It is thought that Sotos syndrome is underdiagnosed because many features associated with the syndrome can also be attributed to other conditions.

A genetic diagnosis of Sotos syndrome can allow the patient to avoid x-rays for bone age and MRI scan of the brain.

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

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
NSD1 NM_022455.4