Chromosome microarray and fragile X testing

Chromosome microarray and fragile X testing are recommended in all individuals with intellectual disability, regardless of presentation. These tests can be requested by any medical practitioner, but are most commonly requested by paediatricians and genetics services as results can be complex to interpret.

Although fragile X syndrome (FXS) is responsible for only about 2% of intellectual disability, it is important not to miss this diagnosis because inheritance is X-linked and consequently there is a high risk of recurrence within families. The phenotypic spectrum of fragile X syndrome is broad and females may appear to be less affected. Fragile X requires a separate DNA test that is not included in chromosome microarray. For more advice, see Diagnosis of fragile X syndrome.

Chromosome microarray has a diagnostic yield of approximately 15% in individuals with developmental disability. Microarray is recommended in individuals with intellectual disability, as well as those with developmental delay, autism spectrum disorder and multiple congenital anomalies. Microarray will detect a broad range of chromosomal causes, including autosomal aneuploidies (eg Down syndrome), sex chromosome abnormalities, and deletions and duplications of parts of chromosomes (ie copy number variants [CNVs]).

Chromosome microarray allows the detection of all of the well-characterised microdeletion syndromes, such as Williams syndrome (7q11.23 deletion) and 22q11.2 deletion syndrome (velocardiofacial syndrome). It has also led to the discovery of a range of new deletion and duplication syndromes that had previously escaped clinical recognition (eg Koolen de Vries syndrome [17q21.31 deletion], Kleefstra syndrome [9q34 deletion]).

Chromosome microarray has led to the identification of approximately 50 copy number variants that are found in the general population, but detected with increased frequency in individuals with neurodevelopmental conditions such as intellectual disability, autism, epilepsy and schizophrenia. These copy number variants affect ‘susceptibility loci’ and increase the risk of neurodevelopmental disorders, but in the absence of additional genetic or environmental factors do not necessarily produce a phenotype. Some of the more common neurodevelopmental susceptibility copy number variants are deletions and duplications at 1q21.1, 15q13.1, 16p11.2, 16p12.1, and 17q12.

Microarray results can be difficult to interpret and it is recommended that individuals with abnormal or uncertain results be referred for genetic counselling.

For more information on chromosome microarray, see the Royal Australian College of General Practitioners (RACGP) guideline Genomics in general practice.

Test results should be clearly recorded in the person’s medical history.