Journal de la maladie d'Alzheimer et du parkinsonisme

Abstrait

Children with Mild CAG Repeat Expansion in HTT Gene Showing Psychiatric but not Neurological Presentation: Is It One More Shade of Huntington Disease?

Massimo Marano, Simone Migliore, Sabrina Maffi, Federica Consoli, Alessandro De Luca, Irene Mazzante and Ferdinando Squitieri

Objective: Huntington disease (HD) generally manifests in adulthood. Large mutations with CAG repeat expansion in HTT gene may rarely cause juvenile Huntington disease (JHD) in early childhood or adolescence with atypical clinical features, i.e., atypical parkinsonism, if compared to adult patients. Our objective is to characterize the rare occurrence of clinical manifestations in children carrying mutations in the low-mild size, generally causing adult HD with typical choreic movements. Methods: We are following up a subgroup of young subjects with HD mutation who manifested with disabling psychiatric condition since early childhood or adolescence. We are collecting data by the observational studies Registry and ENROLL-HD since 2004. Among 60 JHD patients we are currently following-up, we selected people who carry a mutation in the mild range of CAG expansions (i.e., expected to manifest in adulthood), psychiatric manifestations and no neurological signs or movement disorders suggestive of HD. All patients were genetically (i.e., CAG size analysis) and clinically (i.e., total motor score within the Unified HD Rating Scale) characterized. Results: We found four subjects who showed the characteristics for this analysis. All four subjects presented a CAG expansion size <45 repeats. Two patients manifested a schizophrenia-like disturbance during their adolescence, with the later appearance of motor signs after age 20. In the other two cases, patients presented symptoms of autistic spectrum disorder, since infancy. One of them showed also a schizophrenia-like disturbance and, later, HD onset with motor signs after 20. A 45 year old patient is currently manifesting an autistic disorder in absence of others neurological signs. Conclusion: The description of JHD includes sometimes children with psychiatric manifestations associated with adult motor onset. We advise to pay careful attention to such rare conditions that might represent either psychiatric conditions erroneously classified as JHD or prodromic adult HD cases.