Psychiatric and cognitive difficulties as indicators of juvenile huntington disease onset in 29 patients.
BACKGROUND
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.


OBJECTIVE
To evaluate diagnosis delay in patients with JHD and to analyze the clinical and genetic features of JHD.


METHODS
Retrospective clinical and genetic review.


METHODS
Referral center for HD at Salpêtrière Hospital, Paris, France.


METHODS
Twenty-nine patients with HD with onset before or at age 20 years who carried an abnormal CAG repeat expansion in the HD gene.


RESULTS
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.


CONCLUSIONS
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.
Ribaï
Pascale
P
Department of Genetics, Cytogenetics and Embryology, Salpêtrière Hospital, 75013 Paris, France.
Nguyen
Karine
K
Hahn-Barma
Valérie
V
Gourfinkel-An
Isabelle
I
Vidailhet
Marie
M
Legout
Antoine
A
Dodé
Catherine
C
Brice
Alexis
A
Dürr
Alexandra
A
D000293:Adolescent; D000328:Adult; D001284:Atrophy; D001921:Brain / Q000473:pathology; D002648:Child; D003072:Cognition Disorders / Q000209:etiology*; D005220:Fathers; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology*; D008297:Male; D001523:Mental Disorders / Q000209:etiology* / Q000523:psychology; D009035:Mothers; D009069:Movement Disorders / Q000209:etiology; D012189:Retrospective Studies; D013997:Time Factors; D018911:Trinucleotide Repeats