Diagnostic proceeding in Silver-Russell syndrome.

Area of Science:

• Genetics
• Molecular Biology
• Pediatrics

Background:

• Silver-Russell syndrome (SRS) is a growth disorder with unknown etiology.
• Chromosomal aberrations, including those on chromosome 7, are implicated in SRS.
• Maternal uniparental disomy of chromosome 7 (matUPD7) occurs in about 10% of SRS cases.

Purpose of the Study:

• To report on the experiences of uniparental disomy (UPD) testing in patients diagnosed with SRS.
• To suggest a diagnostic algorithm for SRS, focusing on matUPD7 detection.

Main Methods:

• Eighty-six patients with a clinical diagnosis of SRS were screened for matUPD7 using microsatellite typing.
• Patient cohorts were divided into those with confirmed SRS and those with suspected SRS and scarce clinical data.

Main Results:

• Three new cases of matUPD7 were identified.
• Two patients had uniparental heterodisomy 7, and one had uniparental isodisomy 7.
• matUPD7 was found in both clinically characterized and suspected SRS cases.

Conclusions:

• matUPD7 testing should be prioritized for growth-restricted patients with SRS features.
• Combined cytogenetic and molecular genetic tests can detect chromosomal rearrangements and matUPD7 in over 10% of SRS patients.