Juvenile Huntington' Disease: A Case of Paternal Transmission with an Uncommon CAG Expansion

Huntington disease (HD) is caused by a pathologic cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the HTT gene. Typical adult-onset disease occurs with a minimum of 40 repeats. With more than 60 CAG repeats, patients can have juvenile-onset disease (jHD), with symptom onset by the age of 20 years. We report a case of a boy with extreme early onset, paternally inherited jHD, with symptom onset between 18 and 24 months. He was found to have 250 to 350 CAG repeats, one of the largest repeat expansions published to date. At initial presentation, he had an ataxic gait, truncal titubation, and speech delay. Magnetic resonance imaging showed cerebellar atrophy. Over time, he continued to regress and became nonverbal, wheelchair-bound, gastrostomy-tube dependent, and increasingly rigid. His young age at presentation and the ethical concerns regarding HD testing in minors delayed his diagnosis.

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Psychiatric and Cognitive Difficulties as Indicators of Juvenile Huntington Disease Onset in 29 Patients

Archives of Neurology ◽

10.1001/archneur.64.6.813 ◽

2007 ◽

Vol 64 (6) ◽

pp. 813 ◽

Cited By ~ 82

Author(s):

Pascale Ribaï ◽

Karine Nguyen ◽

Valérie Hahn-Barma ◽

Isabelle Gourfinkel-An ◽

Marie Vidailhet ◽

...

Keyword(s):

Huntington Disease ◽

Disease Onset ◽

Cognitive Difficulties ◽

Juvenile Huntington Disease

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Modulation at Age of Onset in Tunisian Huntington Disease Patients: Implication of New Modifier Genes

Genetics Research International ◽

10.1155/2014/210418 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Dorra Hmida-Ben Brahim ◽

Marwa Chourabi ◽

Sana Ben Amor ◽

Imed Harrabi ◽

Saoussen Trabelsi ◽

...

Keyword(s):

Huntington Disease ◽

Neurodegenerative Disorder ◽

Age Of Onset ◽

Age At Onset ◽

Specific Effect ◽

Modifier Genes ◽

Cag Repeats ◽

Causative Mutation ◽

Cag Expansion ◽

Tunisian Patients

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO) of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population.

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I10 Cross-sectional and longitudinal analysis in juvenile huntington disease in italy

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2016-314597.175 ◽

2016 ◽

Vol 87 (Suppl 1) ◽

pp. A62.2-A62

Author(s):

Massimo Marano ◽

Simone Migliore ◽

Sabrina Maffi ◽

Federica Consoli ◽

Ferdinando Squitieri

Keyword(s):

Longitudinal Analysis ◽

Huntington Disease ◽

Cross Sectional ◽

Juvenile Huntington Disease

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Medical genetics: advances in brief: Huntington disease without CAG expansion: phenocopies or errors in assignment?

Journal of Medical Genetics ◽

10.1136/jmg.31.8.656-b ◽

1994 ◽

Vol 31 (8) ◽

pp. 656-656

Author(s):

F. Flinter

Keyword(s):

Huntington Disease ◽

Medical Genetics ◽

Cag Expansion

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The association of CAG repeat length with clinical progression in Huntington disease

Neurology ◽

10.1212/01.wnl.0000204230.16619.d9 ◽

2006 ◽

Vol 66 (7) ◽

pp. 1016-1020 ◽

Cited By ~ 81

Author(s):

A. Rosenblatt ◽

K. -Y. Liang ◽

H. Zhou ◽

M. H. Abbott ◽

L. M. Gourley ◽

...

Keyword(s):

Huntington Disease ◽

Linear Models ◽

Motor Impairment ◽

Repeat Length ◽

Cag Repeat ◽

Clinical Progression ◽

Cag Expansion ◽

Rate Of Progression ◽

State Examination

Objective: To determine whether the rate of clinical progression in Huntington disease (HD) is influenced by the size of the CAG expansion.Methods: The dataset consisted of 3,402 examinations of 512 subjects seen through the Baltimore Huntington's Disease Center. Subjects were seen for a mean of 6.64 visits, with mean follow-up of 6.74 years. Subjects were administered the Quantified Neurological Examination, with its subsets the Motor Impairment and Chorea Scores, the Mini-Mental State Examination, and the HD Activities of Daily Living (ADL) Scale.Results: In an analysis based on the Random Effects Model, CAG length was significantly associated with the rate of progression of all measures except chorea and ADL. There was a significant interaction term between CAG length and disease duration for all measures except chorea. Further graphical exploration of the data supported these linear models and suggested that subjects at the low end of the expanded CAG repeat range may experience a more benign late course.Conclusions: CAG repeat length has a small effect on rate of progression that may be clinically important over time. Individuals with the shortest expansions appear to have the best prognosis. These effects of the CAG length may be relevant in the analysis of clinical trials.

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