Presentation: Clinical suspicion of Huntington disease

A woman in her early 40s attends neurology clinic with a history of depression, progressive movement problems, clumsiness and weight loss. Her family report that she is unable to sit still and is often irritable. Jerky saccades, hyperreflexia and widespread chorea is noted on examination. It is reported that her mother died from suicide but had problems with poor balance and twitching movements prior to that event.

• Genomic testing should be considered if a patient’s clinical features indicate a likely diagnosis of Huntington disease. This testing should be discussed fully with the patient prior to initiation to allow them to understand the implications of a positive test result.
• Clinical presentation of Huntington disease can be variable between individuals, even within the same family, and will alter over time depending on disease stage. Features can include:
  • movement anomalies: chorea, dystonia and ataxia;
  • cognitive anomalies: irritability, apathy and dementia;
  • psychiatric involvement: anxiety, depression and more rarely psychosis; and
  • a family history consistent with autosomal dominant inheritance (though this may not always be present).
• MRI imaging in a patient with symptoms consistent with Huntington disease may include caudate and striatal atrophy; however, the presence of these symptoms is not required for diagnosis.
• Please note that the presentation of juvenile Huntington disease (clinical onset under 20 years of age) is often different to that of the adult-onset form, and if it is suspected, the case should be discussed with a specialist prior to testing.
• Unaffected individuals may present with a family history of an adult-onset genetic condition. Where signs and/or symptoms suggestive of that condition are not present in the patient, they should be offered referral to a local clinical genetics service to discuss testing as part of a predictive (presymptomatic) testing pathway.
• A genetic diagnosis may have implications for other family members, and can be particularly relevant during a pregnancy. For some genetic conditions, rapid testing is available for the purposes of pregnancy management. Assessment of symptoms during pregnancy and discussion of the patient’s choices regarding prenatal testing may be offered. If the patient or a close relative is pregnant, you may wish to offer them a referral to the local clinical genetics service for further discussion.
• Patients and families undergoing testing may wish to seek support through the Huntington’s Disease Association during this process.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria document for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Decide which panel best suits the needs of your patient and/or their family.
  • R68 Huntington disease. This should be used if Huntington disease is the suspected diagnosis. It involves short tandem repeat (STR) testing for the trinucleotide repeat expansion in the HTT gene. This test can only be requested by specialists in neurology, psychiatry and clinical genetics. If the result is negative, you may wish to consider other panels depending on the patient’s clinical presentation.
• R68 does not use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order and consent (record of discussion) forms.
• R68 is DNA based, and an EDTA sample (typically a purple-topped tube) is required. There are a few tests for which a different type of tube is used; see Samples for genomic testing in rare disease.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• NHS England: National Genomic Test Directory

References:

• Craufurd D, Frontali M, MacLeod R and others. ‘Diagnostic genetic testing for Huntingon’s disease’. Practical Neurology 2015: volume 15, issue 1, pages 80–84. DOI: 10.1136/practneurol-2013-000790

For patients

• Huntington’s Disease Association