Microarray Testing

You receive the attached letter about a young patient:

Thank you for referring this 8-year-old girl who has diagnoses of autism and ADHD. She has undergone genomic screening for this via an array CGH test, and she has been found to carry a 16p13.11 micro-duplication. I would be grateful if you could arrange testing for her family for this micro-duplication

Micro-array testing is being used increasingly as an investigation for children with psychological and behavioural disorders, particularly when a child has more than one diagnosis.

A micro-array test is a genomic ‘screen’ looking for chunks of DNA which are either missing or duplicated (micro-deletions and microduplications). Microdeletions and microdulpications are also known as copy number variants (CNV), as they are a variation on the normal number of copies of a chunk of DNA. The numbers describe which chromosome and where in the chromosome the microdeletion or microduplication is.

CNVs in this context are known as neurosusceptibility variants as they are associated with a spectrum of psychological, emotional and behavioural disorders including intellectual disability, autism, epilepsy, attention deficit disorder and learning disabilities. Neurosusceptibility variants show enormously variable penetrance and there is a wide spectrum of severity: some people may never know that they carry a CNV as they have mild or no features. There are only a few neurosusceptbility variants associated with adult-onset health implications; 16p13.11 is one of these as there is an associated risk of Thoracic Aortic Aneurysm and dissection.

This infographic explains micro-array testing.

In primary care, we may become involved in care co-ordination and holistic care for the child, and be requested to address implications for the family. The charity Unique has produced information leaflets for all known neurosusceptilibility variants which are an excellent source of information for patients and healthcare professionals. For example, the rare disorder guide for 16p13.11 micro-duplication.

Genetic counselling for neurosusceptibility variants is complex. There is a high de novo rate, they generally follow an autosomal dominant pattern of inheritance with extremely variable penetrance. Testing of relatives is generally only offered in the UK if an individual is symptomatic, or if screening for an adult-onset medical condition is recommended. In the case of 16p.13.11 regular cardiac surveillance is indicated. Ante-natal testing is not generally offered for the above reasons.

In Rebecca’s family’s case, as detailed in the letter, it would be recommended that the GP write to clinical genetics for advice for the family. Some services may see the family whereas others may not necessarily offer an appointment but give standard advice.