Investigation of suspected chromosome imbalance in patients with learning difficulties multiple congenital abnormalities unexplained epilepsy or other developmental disorders

Introduction

In many patients with unexplained developmental delay, learning difficulties, multiple congenital abnormalities (MCA), behavioural disorders, dysmorphism or other developmental disorders, the conditions are caused by chromosome imbalance due to loss or gain of dosage sensitive genes or disruption of normal gene expression. The imbalance may be due to extra chromosomes (aneuploidy), unbalanced structural rearrangements or submicroscopic deletions or duplications.

Referral information

We accept blood (4ml in EDTA) or mouthwash samples from children and adults with a suspected chromosome imbalance. Follow up testing is also offered to family members of patients who have been diagnosed with chromosome imbalance to establish the inheritance of the imbalance and evaluate reproductive risks.

Microarray Comparative Genomic Hybridisation (aCGH) is used as the frontline test to detect chromosome imbalance. Microarray testing can detect chromosome deletions or gains at a higher resolution than routine chromosome analysis.

Babies and children with referral reasons indicative of aneuploidy (trisomy for chromosomes 13, 18 or 21) or sex chromosome disorders will be processed by QF-PCR in the first instance followed by microarray as a reflex test if a normal result is obtained from QF-PCR.

Microarray testing cannot detect balanced chromosome rearrangements or polyploidy and may not detect unbalanced rearrangements present in mosaic form.

Follow up testing may be performed by microarray, chromosome analysis or Fluorescence In Situ Hybridisation (FISH), as appropriate.

Technical information

Microarray testing is carried out using DNA extracted from the patient sample. The microarray platform currently in use is the OGT CytoSure Constitutional v3 8x60k array. This array uses 60,000 probes across the whole genome. This platform has a minimum and maximum backbone resolution between 663kb and 180kb with enhanced coverage of developmental disorder genes. There may be instances where an accredited test is performed outside the scope of accreditation. Some FISH tests may exceed the manufacturer’s expiry date and are performed outside the scope of accreditation; the test, however, is performed to the same internal quality control standards and procedures and results may be confirmed with alternative FISH probes or by other testing pathways. For further information please contact the laboratory on 0161 276 6553.

Price & reporting times

NHS referrals to this service are paid for where there is an existing specialist commissioning contract for genetic testing. In other cases please contact the lab for prices.

Test Price (£ ex VAT) TRT *
Routine postnatal sample (no follow-up studies) POA 28 cd
Urgent postnatal sample (no follow-up studies) POA 14 cd
Postnatal sample referred with parental sample(s)

(Includes completion of any follow up studies)

POA 56 cd
Parental blood sample for inheritance studies POA 28 cd

Test validation & quality assurance - information for users

The OGT CytoSure Constitutional v3 8x60k microarray is not sold for diagnostic use. Due to probe distribution and density, all sizing information provided on reports is approximate. Anomalies may occur which cannot always be recognised or properly interpreted. Microarray analysis will not detect balanced rearrangements or polyploidy and may not detect unbalanced rearrangements present in mosaic form. aCGH does not provide any positional information. Analysis parameters are subject to change.

Sample requirements

Postnatal: 4ml EDTA blood sample (for microarray) or 4ml Lithium Heparin blood sample for chromosome analysis or FISH.

Referral guidelines

Please see our referral guidelines for more information.

y