The average age of onset in the study was 14. The average delay in getting a diagnosis was 9 years, with a range of 0 to 21 years. The delay was caused by the 'nonspecific' features of onset and in some cases, an absence of family history. By nonspecific, they mean symptoms that are not necessarily indicative of JHD but could be caused by other diseases or problems. Traditionally, Huntington's Disease has been diagnosed by characteristic motor symptoms although cognitive and psychiatric symptoms may have been already present.
Ten children first presented with motor disturbances, nine with psychiatric problems, and ten with cognitive decline. In six of those, the decline in school performance was rapid.
Of those presenting with motor symptoms, none started with rigidity although 21 patients had dystonia at some point and 18 had chorea. The first signs in those presenting with motor symptoms were chorea (3 children), myoclonus (involuntary twitching affecting 3 children), falling (2), handwriting difficulties (1), and twitching of the shoulders (1).
Of those presenting with psychiatric symptoms, three had serious depression, three had substance abuse problems, one had fugue states (doing things without being cognitively aware) and suicide attempts, one was psychotic, and one had a number of behavioral changes. In the group overall, psychiatric problems were serious with seven children attempting suicide.
Although maternal transmission of JHD is usually referred to as rare, one-quarter of the patients had an affected mother. Although the literature usually states that JHD is associated with CAG counts of 60 or higher, nearly half of the patients in the study had between 45 and 58 repeats.
Clearly then, in JHD as with adult HD, there is a substantial variation in onset and clinical progression of the disease. Individuals don't necessarily follow the recognized pattern of symptoms for JHD - motor onset, known family history, paternal transmission, and high CAG repeats.
Biglan and Shoulson provided commentary in the same edition of the journal. They recognize the variability of early symptoms of those with HD and point out that the problem of determining onset is shared with adult Huntington's Disease as well. "Onset of HD in juveniles and adults, while a discrete outcome of intrinsic value to familes and care providers, remains a probabilistic judgment that has yet to be validated prospectively."
With therapies on the horizon, getting data from longitudinal, prospective studies is critical. They describe two ongoing studies for adults, PHAROS and Predict-HD, as well as the newest study COHORT which also includes children.
Kevin Biglan and Ira Shoulson, "Juvenile-Onset Huntington Disease: A Matter of Perspective," Archives of Neurology 2007;64:783-784.
Juvenile Huntington disease (JHD) is a rare clinical entity characterized by an age at onset younger than 20 years. Patients usually have an expansion of more than 60 CAG repeats in the Huntington disease (HD) gene, and the disease is usually inherited from the father. In general, precise age at onset is difficult to assess in HD because of insidious onset and anosognosia. Onset of motor difficulty signs is usually used to define age at onset.
To evaluate diagnosis delay in patients with JHD and to analyze the clinical and genetic features of JHD.
Retrospective clinical and genetic review.
Referral center for HD at Salp?tri?re Hospital, Paris, France. Patients Twenty-nine patients with HD with onset before or at age 20 years who carried an abnormal CAG repeat expansion in the HD gene.
The mean +/- SD delay before diagnosis was 9 +/- 6 years (range, 0-21 years). The most remarkable signs at onset were severe psychiatric and cognitive disturbances (19 of 29 [65.5%]); rigidity was absent. Unusual signs at onset included myoclonic head tremor in 3 patients, severe isolated drug or alcohol addiction in 2, psychotic disorder in 1, and difficulty writing in 1. One patient had progressive cerebellar signs associated with cerebellar atrophy on cerebral magnetic resonance imaging before signs suggestive of HD appeared. During the course of the disease, psychiatric disturbances were severe, with at least 1 suicide attempt in 7 of 29 patients. Transmission was maternal in 25% of patients. Forty-six percent of patients with JHD had fewer than 60 CAG repeats; 6 of these patients inherited the disease from their father. Anticipation (mean +/- SD, 18 +/- 9 vs 25 +/- 11 years; P = .27) and age at onset (mean +/- SD, 17.14 +/- 2.2 vs 13.29 +/- 5.5 years; P = .09) was similar in patients with maternal compared with paternal transmission, respectively.
Patients with JHD started showing disease symptoms through nonspecific features, mostly psychiatric and cognitive difficulties. This led to misdiagnosis or diagnosis delay, especially in cases without a familial history of HD. Maternal transmissions and expansions of fewer than 60 CAG repeats were unexpectedly frequent in this series and should not be considered exceptional.