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CASE REPORT
Year : 2015  |  Volume : 10  |  Issue : 3  |  Page : 276-279
 

Childhood-onset (Juvenile) Huntington's disease: A rare case report


Department of Pediatrics, ESI PGIMSR, ESIC Model Hospital, Andheri, Mumbai, Maharashtra, India

Date of Web Publication18-Sep-2015

Correspondence Address:
Kailash Chandra Patra
1101 Gloriosa Aprtment, Agar Bazar, Dadar, Mumbai - 400 028, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1817-1745.165709

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   Abstract 

Huntington's disease (HD) is a rare dominantly inherited neurodegenerative disorder characterized clinically by a combination of abnormal involuntary (choreic) movements, neuropsychiatric manifestations, and dementia. It is caused by an unstable CAG repeat expansion in the gene IT15 which encodes a Huntingtin protein. We present a case of a 9 year old boy who had developmental regression starting from the age of 8 years of age along with resistant seizures and signs of cerebellar involvement with absence of chorea and is on anticonvulsants, baclofen, and tetrabenzine. As is expected in a case of childhood-onset HD, our patient is rapidly deteriorating and is currently in the terminal phase of his illness along with resistant convulsions.


Keywords: CAG repeat expansion, Juvenile Huntington′s disease, magnetic resonance imaging, polymerase chain reaction


How to cite this article:
Patra KC, Shirolkar MS. Childhood-onset (Juvenile) Huntington's disease: A rare case report. J Pediatr Neurosci 2015;10:276-9

How to cite this URL:
Patra KC, Shirolkar MS. Childhood-onset (Juvenile) Huntington's disease: A rare case report. J Pediatr Neurosci [serial online] 2015 [cited 2020 Oct 22];10:276-9. Available from: https://www.pediatricneurosciences.com/text.asp?2015/10/3/276/165709



   Introduction Top


Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder characterized clinically by a combination of abnormal involuntary (choreic) movements, neuropsychiatric manifestations, and dementia. [1] Its prevalence in various areas of the world ranges from 5 to 10 per 100,000. [1]

The onset of disease <20 years of age is classified as Juvenile HD (JHD) and those with disease onset <10 years are described as having "Childhood-onset HD." [2]

The disease is caused by an unstable CAG repeat expansion in the gene IT15, which encodes a protein of unknown function known as Huntingtin. [1]

The characteristics of JHD differ from those of adult-onset HD, as chorea does not occur in JHD although bradykinesia, dystonia, and signs of cerebellar disorder such as rigidity are present frequently in association with convulsive episodes and psychotic manifestation. [3]


   Case Report Top


Our patient is a 9-year-old male child, first by birth order, born of nonconsanguineous marriage who was developmentally normal till 8 years of age when he suddenly developed episodes of frequent falls, ataxic gait and bradykinesia following which one day he had generalized tonic-clonic seizures which were refractory to anticonvulsants. Over the period of few months the parents noticed a loss of achieved developmental milestones to a current developmental age of 1.5-2 years. There is also regression of language milestones to a current status of just monosyllable speech. Inspite of multiple anticonvulsants the child still has persistent seizures. There was no history of any abnormal movements, psychiatric manifestations, and no other members are affected in the family.

On examination, the child had ataxic gait, bradykinesia, oculomotor apraxia, rigidity, and signs of cerebellar involvement. Fundus examination was normal. However, there was no chorea, microcephaly, facial dysmorphism, or hepatosplenomegaly.

On investigation, electroencephalography (EEG) was normal. Magnetic resonance imaging (MRI) brain showed hyperintensity involving caudate nucleus and putamen on both sides with atrophy and volume loss suggestive of JHD [Figure 1]. Positron emission tomography (PET) scan showed severe hypometabolism in bilateral striatum suggestive of JHD. DNA polymerase chain reaction showed 83 expanded trinucleotide CAG repeat sequences.

The patient is currently on three anticonvulsants (sodium valproate, levetiracetam, and topiratmate), a muscle relaxant (baclofen) and tetrabenzine. But, inspite of this the patient has frequent seizures and has a rapid deteriorating course and is bedridden at present.
Figure 1: T2 axial image showing bliateral symmetrical hyperintensity in the caudate (C) and putamen (P) with volume loss and mild atrophy

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   Discussion Top


In 1872 George Huntington in his original article described HD [1] and also stated that he does not know even a single case that has shown any marked signs of chorea before the age of 30 or 40 years. [1],[4] But in retrospect, it became known that in 1863, that is, 9 years before Huntington's report, Lyon published the first case of childhood HD. [1],[5] Onset of HD in children younger than 10 years was first described by Harbinson in 1880. [1],[6]

Any patient with HD will experience a mixture of problems with both voluntary and involuntary movements. Classically, patients with adult HD will demonstrate signs of chorea early in the course of illness whereas in JHD, the pattern tends to be that of bradykinesia, dystonia and Parkinsonian features which are prominent at an early stage while chorea, if present, is less prominent. [2],[7] Our patient has a similar presentation.

Diagnostic criteria for childhood-onset HD (≤10 years). [2],[8]

A family history of HD (usually in the father) and two or more of:

  • Declining school performance
  • Seizures
  • Oral-motor dysfunction
  • Rigidity
  • Gait disturbance.


Our patient had seizures, oral-motor dysfunction, rigidity, and gait disturbance, but there was no history of declining school performance and neither a family history of HD. Speech and language problems may occur early in the course of illness and can be a pointer toward the diagnosis [2] which is there in our case.

Summary of HD symptoms that require treatment:

Movement disorder

  • Involuntary movements
  • Incoordination of voluntary movements
  • Rigidity/dystonia
  • Oral-motor dysfunction.


Cognitive disorder

  • Progressive cognitive dysfunction (treated by repeated testing, and creation of appropriate school or vocational programs and goals).


Psychological/behavioral disorder

  • Depression
  • Anxiety
  • Obsessiveness
  • Inattention/ADHD
  • Apathy
  • Impulsiveness
  • Irritability.


Family issues

  • Caregiver stress
  • School placement
  • Work placement.


Other

  • Weight loss
  • Poor oral hygiene
  • Aspiration pneumonia (late).


The course of childhood-onset HD is a rapid downhill course [1] as is in our patient.

Three phase of childhood-onset HD have been described:

  • An initial phase of behavioral disorder, learning difficulty, gait disturbance, and mild chorea
  • A florid phase with signs of mental deterioration, rigidity, speech disturbance, and seizures
  • A terminal phase of bed confinement, hypotonia and increasing seizures. [1]


In general the younger the age at onset, the shorter the survival. [1]

On genetic analysis, CAG repeat lengths >60 suggests JHD. [2] Our patient had 83 CAG repeats.

In the majority of JHD cases, the transmitting parent is the father [2] because of instability in the CAG repeat length during spermatogenesis which increases if the father has a longer CAG repeat length, [2] but in our case none of family members were affected.

MRI findings seen in HD include changes in the volume of the striate and other cerebral regions such as the thalamus, hippocampus, amygdala, hypothalamus, cerebellum, and frontal and insular cortex as well as atrophy of the caudate and putamen. [3] In our case, the patient had bilaterally symmetrical hyperintensity in the caudate and putamen with volume loss and mild atrophy as shown in the adjoining [Figure 1].

PET scans are more sensitive and specific of JHD amd include marked hypometabolism in the caudate and putamen nuclei and posterior thalamic nuclei. [1],[9],[10],[11],[12],[13] In our patient, we had hypometabolism in bilateral striatum suggestive of JHD.

Currently, EEG is usually less useful in JHD and shows paroxysmal features. [1]


   Treatment Top


At present, there is no definitive treatment for HD. [3],[14],[15] However, we started with antiepileptics (sodium valproate, levetiracetam, and topiramate) for resistant seizures, baclofen for muscle relaxation and tetrabenzine as a symptomatic treatment for our patient.

The following drugs could be given although questions remain regarding their safety. Typical antipsychotics (haloperidol and pimozide) improve chorea at the expense of deteriorating voluntary movements. NMDA receptors antagonists (riluzole and amantadine) have been used experimentally for the treatment of motor disorders. Also, combination of haloperidol and lithium carbonate may control irritability and impulsivity better than monotherapy and risperidone has been shown to improve abnormal involuntary movements and psychotic clinical manifestations. Olanzapine appears to be a good alternative particularly for the control of psychiatric manifestations. [3]

Noteworthy experimental therapies include drugs that prevent aggregation of Huntingtin protein (drosophila), [3],[16] gene therapy (intracellular antibodies [3],[17] and RNAi [3],[18] ), neurotrophic [3],[19] and neuroprotective factors such as coenzyme Q10 [3],[20],[21] and transplantation of striate fetal cells with the aim of delaying or reversing HD.

Acknowledgment

The authors would like to thank Dean of ESI-PGIMSR Andheri, for granting permission to publish this manuscript and Dr. Abhishek Keraliya (Radiologist at ESI PGIMSR) for MRI reporting.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Gonzalez-Alegre P, Afifi AK. Clinical characteristics of childhood-onset (Juvenile) Huntington disease: Report of 12 patients and review of the literature. J Child Neurol 2006;21:223-9.  Back to cited text no. 1
    
2.
Quarrell OW, Nance MA, Nopoulos P, Paulsen JS, Smith JA, Squitieri F. Managing Juvenile Huntington′s disease. Neurodegener Dis Manag 2013;3:267-76.  Back to cited text no. 2
    
3.
Reyes Molón L, Yáñez Sáez RM, López-Ibor Alcocer MI. Juvenile Huntington′s disease: A case report and literature review. Actas Esp Psiquiatr 2010;38:285-94.  Back to cited text no. 3
    
4.
Huntington G. On chorea. Adv Neurol 1973;1:33-35.  Back to cited text no. 4
    
5.
Lyon JW. Chronic hereditary chorea. Am Med Times 1863;7:289-90.  Back to cited text no. 5
    
6.
Harbinson A. Sclerosis of the nervous centers, mainly cerebral. Med Press Circ 1880;29:123-5.  Back to cited text no. 6
    
7.
Quarrell OW. Juvenile Huntington′s disease. In: Bates G, Jones L, Tabrizi S, editors. Huntington′s Disease. 4 th ed. New York, USA: Oxford University Press; 2014. [In Press].  Back to cited text no. 7
    
8.
Nance MA. Genetic testing of children at risk for Huntington′s disease. US Huntington Disease Genetic Testing Group. Neurology 1997;49:1048-53.  Back to cited text no. 8
    
9.
Lenti C, Bianchini E. Neuropsychological and neuroradiological study of a case of early-onset Huntington′s chorea. Dev Med Child Neurol 1993;35:1007-10.  Back to cited text no. 9
    
10.
Kuhl DE, Phelps ME, Markham CH, Metter EJ, Riege WH, Winter J. Cerebral metabolism and atrophy in Huntington′s disease determined by 18FDG and computed tomographic scan. Ann Neurol 1982;12:425-34.  Back to cited text no. 10
    
11.
Young AB, Penney JB, Starosta-Rubinstein S, Markel DS, Berent S, Giordani B, et al. PET scan investigations of Huntington′s disease: Cerebral metabolic correlates of neurological features and functional decline. Ann Neurol 1986;20:296-303.  Back to cited text no. 11
    
12.
Mazziotta JC, Phelps ME, Pahl JJ, Huang SC, Baxter LR, Riege WH, et al. Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington′s disease. N Engl J Med 1987;316:357-62.  Back to cited text no. 12
    
13.
Young AB, Penney JB, Starosta-Rubinstein S, Markel D, Berent S, Rothley J, et al. Normal caudate glucose metabolism in persons at risk for Huntington′s disease. Arch Neurol 1987;44:254-7.  Back to cited text no. 13
    
14.
Bonelli RM, Hofmann P. A review of the treatment options for Huntington′s disease. Expert Opin Pharmacother 2004;5:767-76.  Back to cited text no. 14
    
15.
Hannan AJ. Novel therapeutic targets for Huntington′s disease. Expert Opin Ther Targets 2005;9:639-50.  Back to cited text no. 15
    
16.
Hughes RE, Olson JM. Therapeutic opportunities in polyglutamine disease. Nat Med 2001;7:419-23.  Back to cited text no. 16
    
17.
Alvarez RD, Barnes MN, Gomez-Navarro J, Wang M, Strong TV, Arafat W, et al. A cancer gene therapy approach utilizing an anti-erbB-2 single-chain antibody-encoding adenovirus (AD21): A phase I trial. Clin Cancer Res 2000;6:3081-7.  Back to cited text no. 17
    
18.
Caplen NJ, Taylor JP, Statham VS, Tanaka F, Fire A, Morgan RA. Rescue of polyglutamine-mediated cytotoxicity by double-stranded RNA-mediated RNA interference. Hum Mol Genet 2002;11:175-84.  Back to cited text no. 18
    
19.
Qin ZH, Wang J, Gu ZL. Development of novel therapies for Huntington′s disease: Hope and challenge. Acta Pharmacol Sin 2005;26:129-42.  Back to cited text no. 19
    
20.
Philpott LM, Kopyov OV, Lee AJ, Jacques S, Duma CM, Caine S, et al. Neuropsychological functioning following fetal striatal transplantation in Huntington′s chorea: Three case presentations. Cell Transplant 1997;6:203-12.  Back to cited text no. 20
    
21.
Bachoud-Lévi AC, Rémy P, Nguyen JP, Brugières P, Lefaucheur JP, Bourdet C, et al. Motor and cognitive improvements in patients with Huntington′s disease after neural transplantation. Lancet 2000;356:1975-9.  Back to cited text no. 21
    


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