IriSight® Case Study
Overview
Patient:
34 year-old, 20 weeks gestation
Clinical presentation:
Cystic hygroma, distended jugular lymphatic sacs, bilateral fetal pyelectasis, hypertelorism
Testing strategy:
Variantyx whole genome testing
Key finding:
Pathogenic 10q11.22-q11.23 4.3 Mb maternally inherited heterozygous deletion
Pathogenic maternally inherited heterozygous c.1403C>T variant in the PTPN11 gene
Clinical outcome:
Dual diagnosis established
Why IriSight® was the right choice
An anatomy scan at 20 weeks identified cystic hygroma with additional anomalies. Prior chromosomal microarray (CMA) testing identified an ~4.6 Mb 10q11 deletion, however the clinician found this to be an insufficient explanation for the observed findings. Particularly in the context of the parents’ medical histories which included a May-Thurner syndrome diagnosis and hereditary spherocytosis.
IriSight® was selected because it delivers the most comprehensive genomic insights from the start:
- Reducing time to diagnosis
- Avoiding unnecessary testing
- Supporting the highest standard of patient care
Diagnostic finding: 10q11.22 deletion syndrome, PTPN11-related disorders
Variantyx IriSight® testing identified the heterozygous, maternally inherited, pathogenic 4.3 Mb deletion within chromosome 10q11.22 to 10q11.23. Plus a heterozygous, maternally inherited, pathogenic c.1403C>T variant in the PTPN11 gene consistent with the fetal findings.
Noonan syndrome, the most common autosomal dominant PTPN11-related disorder, and 10q11.22 deletion syndrome are both associated with significant variable expressivity.
Impact on clinical care
Provided a dual diagnosis and enabled maximally informative future reproductive planning.
Spotlight on comprehensive testing
Challenges
Stepwise testing that begins with CMA will always require a second test to rule in or rule out small sequence changes that fall below the threshold of CMA detection.
Why IriSight®
- Has a detection range from 1 bp to whole chromosomal events, easily detecting copy number variants and single nucleotide changes in a single test
- Enables dual diagnosis of disorders caused by different variant types
Additional similar cases
IriSight® – Deep intronic SNRPB variant explains micrognathia, retrognathia & polyhydramnios
IriSight® – Elective testing identifies homoplasmic mitochondrial variant inherited from heteroplasmic mother
IriSight® – MED12 SNV links observed congenital diaphragmatic hernia to Hardikar syndrome diagnosis