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, +/- 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
NSD1 NM_022455.4