Levodopa-responsive dystonia, parkinsonism, and treatment-resistant schizoaffective disorder in Williams syndrome

• Published in: Neurological sciences 2025-01, Vol.46 (1), p.463-468
• Main Authors: Reyes, Nikolai Gil D., Bendahan, Nathaniel, Swinkin, Emily, Lang, Anthony E., Bassett, Anne S.
• Format: Article
• Language: English
• Subjects: Adult; Antipsychotic Agents - therapeutic use; Antipsychotics; Basal ganglia; Central nervous system diseases; Chromosome 7; Chromosome deletion; Clinical trials; Clozapine; Dystonia; Dystonic Disorders - drug therapy; Female; Humans; Intellectual disabilities; Levodopa; Levodopa - adverse effects; Levodopa - therapeutic use; Male; Medicine; Medicine & Public Health; Mental disorders; Movement disorders; Neurodevelopmental disorders; Neuroimaging; Neurology; Neuroradiology; Neurosurgery; Parkinsonian Disorders - drug therapy; Phenotypes; Psychiatry; Psychotic Disorders - drug therapy; Psychotic Disorders - etiology; Psychotropic drugs; Schizoaffective disorder; Schizophrenia; Short Paper; Williams syndrome; Williams Syndrome - complications; Williams Syndrome - drug therapy
• ISSN: 1590-1874; 1590-3478; 1590-3478
• DOI: 10.1007/s10072-024-07705-3

Background Williams syndrome (WS; chromosome 7q11.23 deletion) is a rare, multisystemic, neurodevelopmental disorder with variable penetrance and expressivity. Although movement and psychiatric disorders are known to occur in individuals with WS, parkinsonism, dystonia, and treatment-resistant schizoaffective disorder have not been formally described. Methods We present two unrelated cases of adults with molecularly confirmed WS and typical histories of developmental delays, intellectual/learning disabilities, and treatment-responsive anxiety/mood disorder who developed similar noteworthy neuropsychiatric expressions. We reviewed detailed neuropsychiatric histories, laboratory investigations, neuroimaging, and treatment responses and compared data for the two cases. Results Both individuals developed treatment-resistant schizoaffective disorder in adulthood requiring multiple trials of antipsychotic treatments. While on clozapine, both patients developed parkinsonism and generalized dystonia with truncal involvement that responded to trials of low-dose levodopa without exacerbating underlying psychotic or affective symptoms. Conclusion This report illustrates the novel occurrence of levodopa-responsive movement disorders and treatment-resistant schizoaffective disorder in individuals with WS, adding to the expanding neuropsychiatric phenotypes, and highlighting potential shared underlying mechanisms. The observed treatment response suggests that levodopa, in relatively low doses, may be safe and useful in ameliorating presumed antipsychotic-associated parkinsonism and tardive dystonia in WS.