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\b\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 JUVENILE HUNTINGTON DISEASE (JHD) PRESENTING AS PROGRESSIVE SPEECH IMPAIREMENT
\par Nina Canki-Klain
\par }{\cs15\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 ZAGREB UNIVERSITY SCHOOL OF MEDICINE}{\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 , }{
\cs15\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 Croatian Institute for brain research
\par University Medical Centre\~ Rebro, Department of Neurology
\par 
\par }\pard \ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10163868 {\b\f36\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid3489628 Background}{\f36\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 
. Huntington disease (HD) is an autosomal dominant, lethal neurodegenerative disorder of the central nervous system. It is caused by an uncontrolled expansion of a CAG }{\f36\lang1033\langfe1036\langnp1033\insrsid5721975\charrsid5721975 dynamic mutation}{
\f36\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 
 in the coding region of the IT 15gene. CAG repeat is translating as a polyglutamine expansion in the huntingtin protein, whose main pathogenic mechanism is a gain of toxic function. In the case of large expansion beyon
d 60 repeats onset may result in JHD. Although a majority of patients have a midlife onset of symptoms, in a small number of patients }{\f36\lang1033\langfe1036\langnp1033\insrsid14493073 (}{\f36\lang1033\langfe1036\langnp1033\insrsid14493073 
{\field{\*\fldinst SYMBOL 60 \\f "Symbol" \\s 12}{\fldrslt\f3\fs24}}}{\f36\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 10%) disease can manifests before 20 years of age as early onset or JHD. In adults, HD is mainly }{
\f36\lang1033\langfe1036\langnp1033\insrsid5721975\charrsid5721975 characterized}{\f36\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 
 by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability and dementia. In contrast to patients with adult }{\f36\lang1033\langfe1036\langnp1033\insrsid5721975\charrsid5721975 onset}{
\f36\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 , in which chorea is the major motor abnormality, children }{\f36\lang1033\langfe1036\langnp1033\insrsid5721975\charrsid5721975 often present}{
\f36\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975  with spasticity, }{\f36\lang1033\langfe1036\langnp1033\insrsid5721975\charrsid5721975 rigidity,}{\f36\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 
 and significant intellectual decline associated with more progressive course. The earlier onset is often associated with a paternal transmission of the disease allele to the offspring. We report here a rather unusual juvenile onset of 
the disease in a little boy who presented with a history of speech impairment starting at the age of 4 years. During three years discrete ataxic gait and bradykinesia have progressed to rigidity, frequent myoclonus, and impossibility to walk}{
\f36\lang1033\langfe1036\langnp1033\insrsid12191117  }{\f36\fs22\lang1033\langfe1036\langnp1033\insrsid12191117 and speak}{\f36\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 . 
\par }{\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 
\par }{\b\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid4290958 Aims.}{\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 
 A paucity of literature with  JHD patients presenting early in life as dysarthria has initiated us to present a  case report of one 7 years 5 months of age boy followed up during three last years. Last not least to point out the necessity of better i
nformation of andrologists /gynecologists about HD in case of male reduced fertility.
\par 
\par }{\b\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid13973060 Methods.}{\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 
 Family study; CT and MRI of brain; molecular analysis of deceased father and affected son; clini}{\f36\fs22\lang1033\langfe1036\langnp1033\insrsid15670998 cal follow up}{\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 .
\par 
\par }{\b\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid3419012 Results.}{\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975  Molecular analysis o
f father demonstrated 43 triplet repeats on one allele and 25 on the other. The son had 19 and 99 CAG repeats, respectively. A marked cerebellar atrophy, a progressive cortical-subcortical atrophy and lesions in the basal ganglia were found on MRI. 

\par 
\par }{\b\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid926483 Discussion.}{\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 
 Evident anticipation with paternal imprinting in four generation studied HD family. Molecular analysis in the son and the father confirms close correlation between size of CAG expansion with clinical features and disease\rquote s progression. 
\par }{\b\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid926483 Conclusion}{\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 . }{\f36\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 
JHD should be considered in small children suffering from progressive speech }{\f36\lang1033\langfe1036\langnp1033\insrsid5721975\charrsid5721975 impairment}{\f36\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 .}{
\f36\fs22\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 
\par }\pard \ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\lang1033\langfe1036\langnp1033\insrsid10163868\charrsid5721975 
\par }}