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24-02-2013 | Genetics | Article

Symptoms poor guide to testing for juvenile Huntington disease


Free abstract

medwireNews: The onset or presentation of specific clinical features that are typical of juvenile Huntington's Disease (JHD) do not help physicians to diagnose the condition without genetic testing.

While rigidity, psychiatric disturbance, cognitive disturbance, and epilepsy are features that are characteristic of JHD, they can also occur in suspected cases that turn out to lack HD's signature genetic cause, CAG expansion, shows a study in Neurology.

"The specific nature of symptoms at onset or at presentation is of limited value in guiding the decision to test or not to test [for HD]," Georgios Koutsis (University of Athens, Greece) and colleagues conclude. "With no family history of HD, JHD is very unlikely and genetic testing should never delay searching for other causes."

The research team analyzed clinical and genetic characteristics of 76 patients with symptoms that were suggestive of HD and that arose before the age of 20 years. The age of onset was retrospectively determined from when the first clinical feature suggestive of HD became clearly manifest.

These patients were further divided into an infantile onset (before 10 years, n=30) and adolescent onset (after 10 years, n=46) to relate clinical manifestations to age.

Of the 76 juvenile-onset cases, 24 (31.6%) tested positive for CAG expansion and had a genetically verified family history of HD. Notably, 13.5% of the 52 patients without the expansion also had a genetically verified family history of HD.

Altogether, family history of genetically confirmed HD alone had 100% sensitivity and 86.5% specificity in differentiating between expansion-positive and negative cases. Conversely, not a single clinical symptom or the manner in which they presented at disease onset enabled the researchers to tell these cases apart within the total cohort and between the infantile and adolescent subgroups - even when several possible symptom combinations were assessed.

"Although a positive family history of HD is a strong predictive factor for JHD, it is by no means a sufficient criterion for diagnosing HD in a symptomatic child at risk for the disease," the authors caution. "It is, therefore, recommended that symptomatic children with a family history of HD be tested without delay so that those negative for the expansion are identified early."

In an accompanying editorial, Rebecca Lehman (Medical University of South Carolina, Charleston) and Martha Nance (Hennepin County Medical Center, Minneapolis, Minnesota) recognize the balancing act of diagnosing HD in teenagers without incorrectly attributing symptoms to HD. They suggest a prudent approach of "a brief period of watchful waiting… to confirm a progressive course" while documenting the patient's cognitive baseline.

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Peter Sergo, medwireNews Reporter

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