Juvenile Huntington's disease: Does a dosage-effect pathogenic mechanism differ from the classical adult disease?

  title={Juvenile Huntington's disease: Does a dosage-effect pathogenic mechanism differ from the classical adult disease?},
  author={Ferdinando Squitieri and Luigi Frati and Andrea Ciarmiello and Secondo Lastoria and Oliver W J Quarrell},
  journal={Mechanisms of Ageing and Development},
Genetics and neuropathology of Huntington's disease.
Huntington’s Disease: Relationship Between Phenotype and Genotype
The recent advancement on the genotype-phenotype relationship of HD is reviewed, mainly focus on the characteristics of different expanded CAG repeat number, genetic modifiers, and CCG repeat number in the 3′ end of CAG triplet repeat and their effects on the phenotype.
Huntington Disease as a Neurodevelopmental Disorder and Early Signs of the Disease in Stem Cells
The early molecular pathogenesis of HD in pluripotent and neural stem cells, with respect to the neurodevelopmental aspects of HD, is discussed.
Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son.
A six-year-old boy with paternally-inherited JHD caused by 169 CAG trinucleotide repeats who presented at age four with developmental delay, dysarthria, and seizures before dying at age 6 is reported.
Clinical features of Chinese patients with Huntington's disease carrying CAG repeats beyond 60 within HTT gene
Clinical features of Chinese HD patients with an expanded CAG repeat over 60 may help the clinicians make a correct diagnosis in the early stage of disease and may help patients with epilepsy, intellectual decline, tics and walking instability be diagnosed correct.
Late-onset Huntington’s disease with 40–42 CAG expansion
There were no clinical differences between CO and LO subgroups with 40–42 CAG expansion and there is a need of further studies on environmental as well genetic variables modifying the age at onset.
Children with Mild CAG Repeat Expansion in HTT Gene Showing Psychiatric but not Neurological Presentation: Is It One More Shade of Huntington Disease?
The description of JHD includes sometimes children with psychiatric manifestations associated with adult motor onset, and is advised to pay careful attention to such rare conditions that might represent either psychiatric conditions erroneously classified as JHD or prodromic adult HD cases.
Juvenile Huntington disease in Argentina.
The findings reinforce the hypothesis that clinical manifestations of juvenile Huntington disease, other than the typical movement disorder, may anticipate age at onset of even many years, and may explain new potential correlations between HD presentations and environmental or biological factors.
Managing juvenile Huntington's disease.
The authors will review what is known of the condition and present some suggestions based on their experience to help clinician managing the patient for the first time.
Juvenile‐Onset Huntington Disease Pathophysiology and Neurodevelopment: A Review
Clinical and pathological features in juvenile‐ and adult‐onset Huntington disease are compared and the interaction of a neurodegenerative disease and postnatal brain maturation is studied to explore which processes potentially contribute to the observed differences.


CAG mutation effect on rate of progression in Huntington's disease
The CAG expanded repeat affects the disease progression only at a very upper pathological range and in rare cases initiating very early in the life, while it does not seem to affect in any way the severity of the phenotype in most HD patients.
Juvenile Huntington's disease: report of one case.
  • W. SueW. HwuC. Y. Chen
  • Medicine, Biology
    Zhonghua Minguo xiao er ke yi xue hui za zhi [Journal]. Zhonghua Minguo xiao er ke yi xue hui
  • 1998
One case that instead of choreoathetosis presents symptoms of developmental regression, such as seizure and rigid/bradykinesia is reported, which is the first case of juvenile Hunington's disease reported in Taiwan.
Evidence for the GluR6 gene associated with younger onset age of Huntington’s disease
This study confirms that the 155 allele is associated with younger onset age of HD and suggests that it is in linkage disequilibrium with a variant of the GluR6 gene or another gene in this region.
Molecular analysis of juvenile Huntington disease: the major influence on (CAG)n repeat length is the sex of the affected parent.
It is demonstrated that the sex of transmitting parent is the major influence on trinucleotide expansion and clinical features in juvenile Huntington disease.
Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines
It is shown that lymphoblast mitochondria from patients with HD have a lower membrane potential and depolarize at lower calcium loads than do mitochondriaFrom controls, and mitochondrial calcium abnormalities occur early in HD pathogenesis and may be a direct effect of mutant huntingtin on the organelle.
The gender effect in juvenile Huntington disease patients of Italian origin
  • M. CannellaC. Gellera F. Squitieri
  • Biology
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2004
The findings suggest the occurrence of a weaker effect of the paternal mutation on juvenile age at onset in this population, possibly amplified by other genetic factors, such as the TAA‐triplet length in the GluR6 gene.
Huntington disease in children: genotype-phenotype correlation.
Large CAG expansions with intergenerational instability were identified, and in one case the child's allele was almost three times larger than the allele of the asymptomatic transmitting father, a situation reported only once before.
Early onset Huntington disease: a neuronal degeneration syndrome
A rather unusual infantile onset of the disease is reported in a little girl who presented with a history of seizures and psychomotor regression starting at the age of 3 years, and an important expansion of the CAG repeat size associated with HD was observed.