Presentation: Patient needing parental genetic blood samples after child’s microarray result

You see a couple with their six-year-old son. He has global developmental delay and his recent microarray test revealed a 16q11.2 microduplication. The parents have received a letter from the paediatrics team requesting a referral to clinical genetics to arrange genomic testing for the microduplication. They are also keen to know if any future children may be affected.

Inherited microdeletions and microduplications usually follow an autosomal dominant pattern. Testing the parents is important for the following reasons:

• To aid prediction of recurrence. CNVs generally follow an autosomal dominant inheritance pattern, meaning that future offspring will have a 1 in 2 (50%) chance of inheriting the CNV. However, if the variant has arisen for the first time in the affected child (de novo), the likelihood of recurrence in a subsequent pregnancy is extremely small.
• To provide further clarity to the significance of the variant if this is unknown. For example, if an unaffected parent shares the same variant as a severely affected child, this may indicate that the variant is a benign CNV that is less likely to be contributing significantly to the affected child’s phenotype.
• If the same finding is identified in a parent, a conversation can be had about whether they have also experienced difficulties relating to the variant, and support and appropriate clinical management can be provided (although the number of CNVs with clinical implications in adulthood is very small).
• Several recurrent CNVs that confer an increased risk of neurodevelopmental conditions (neuro-susceptibility loci) have been identified. It should be noted that antenatal testing is generally not offered in this context due to the widely variable expressivity and heterogeneity of the associated clinical features; the spectrum of clinical features ranges from asymptomatic to significantly affected.

• Arrangements required for any onward referral and consent processes for the investigation and the taking of the sample may vary, so refer to local pathways. If onward referral is needed, include details of the affected child in the referral letter.
• Provide ongoing support and clinical care to the child and family. The charity Unique provides helpful and comprehensive patient resources detailing potential clinical features for all CNVs.
• Letters may contain recommendations for clinical management of adult-onset complications, for example there is an association with thoracic aortic aneurysm for carriers of 16p13.1 microduplication.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.

For clinicians

• NHS England: National Genomic Test Directory
• NHS Genomic Medicine Service: Record of discussion regarding genomic testing
• Unique
• Unique: Microarray-based comparative genomic hybridisation (PDF, 12 pages)

For patients

• Manchester University NHS Foundation Trust: A microarray test: Information for patients (PDF, 4 pages)
• Unique
• Unique: Microarray-based comparative genomic hybridisation (PDF, 12 pages)