F003 Defining the intermediate allele phenotype

<h3>Background</h3> Intermediate alleles (IA), defined as CAG repeats 27–35, have been described associated with Huntington’s disease (HD) signs.^{1 2} Here we report clinical and radiological features of three patients carrying IA. <h3>Case History 1</h3> A 62-year-old woman after 8 years of cervical dystonia presented hyperkinetic movements, anxiety, depression, memory deficits, impaired executive functions and constructive apraxia. Brain MRI showed basal ganglia calcifications (figure 1). Genetic testing for HD revealed 29 triplets. Family history was unremarkable. <h3>Case History 2</h3> A 68-year-old man after traumatic subdural hematoma, surgically treated, developed postural instability and frequent falls. Five years later he developed generalized choreic movements, deficits in verbal fluency, executive functions, attention, memory, and anxiety and depression. Brain MRI showed globus pallidus calcifications (figure 1). Genetic testing for HD revealed 29 repetitions. Family history was unremarkable. <h3>Case History 3</h3> A woman with family history of HD presented since her 50s a severe anxiety-depressive disorder with intrusive thoughts. At age 72 she developed postural and intentionalhands tremor and cautious gait. Deficits in verbal fluency, executive functions, attention and memory emerged. Genetic testing for HD showed 35 repeats. <h3>Conclusions</h3> Our patients presented a long history of movement and psychiatric disorders before the onset of choreic movements, as reported in literature.¹ Initial symptoms might represent early disease stages or predisposing factors. It could be speculated that head trauma, neurosurgery, or pre-existing movement disorders may cause suffering leading to CAG somatic expansion and, clinically, to the onset of HD phenotype. In the absence of specific HD biomarkers it is challenging to define the role of IA in determining patient’s phenotype. <h3>References</h3> Savitt D, Jankovic J. Clinical phenotype in carriers of intermediate alleles in the huntingtin gene.<i> J. Neurol. Sci</i>. 2019;<b>402</b>:57–61. Jevtic SD, Provias JP. Case report and literature review of Huntington disease with intermediate CAG expansion.<i> BMJ Neurol. Open</i> 2020;<b>2</b>:e000027.