Objective: To present a case of Huntington Disease-Like 2 (HDL2). HDL2 is rare and phenotypically similar to Huntington’s Disease (HD). However the gene, chromosome, and repeat expansion are distinct.

Background: The patient is a 72 year-old African American male whose symptoms have been progressing over 10 years. He initially presented with hallucinations, abnormal movements in the left arm, head nodding, and frequent throat clearing. The patient’s symptoms progressed to severe dysarthria, choreiform movements in his legs and lips. He is now wheelchair-bound. Family history is significant for multiple family members diagnosed with HD.

Method: Patient underwent brain MRI, neuropsychological testing, and targeted genetic analysis for pathogenic variants. Additionally, a pedigree and a review of the literature is presented.

Results: MRI brain showed supratentorial involutional changes disproportionate to the patient’s age. Neuropsychological testing revealed deficits in memory (1st percentile), abstract reasoning (2nd percentile), and nonverbal skills (2nd percentile). The overall score was below the 1st percentile. Targeted genetic analysis for pathogenic variants found 42 repeats of CAG/CTG in junctophilin-3 (JPH3) gene, which confirmed the diagnosis of HLD2.

Conclusion: While similar in phenotype to HD, HDL2 is caused by an expansion of CAG/CTG triplets in exon 2A of the JPH3 gene on chromosome band 16q24. HDL2 is a neurodegenerative disease without any disease-modifying pharmacological treatment, which progresses to death 10 to 20 years from diagnosis. Given the recent development of promising disease-modifying therapies for HD, it will become increasingly important from a clinical perspective to identify patients who will not respond to therapy due to differences in genotype.

References: 1. Anderson DG, Walker RH, Connor M, Carr J, Margolis RL, Krause A. A Systematic Review of the Huntington Disease-Like 2 Phenotype. Huntingtons Dis. 2017;6(1):37-46. 2. Rodrigues GG, Walker RH, Brice A, Cazeneuve C, Russaouen O, Teive HA, Munhoz RP, Becker N, Raskin S, Werneck LC, Junior WM, Tumas V. Huntington’s disease-like 2 in Brazil-report of 4 patients. Mov Disord. 2008 Nov 15;23(15):2244-7.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/huntington-disease-like-2-a-case-presentation-and-review-of-the-literature/