Early-onset parkinsonism in PPP2R5D-related neurodevelopmental disorder.
PPP2R5D-related neurodevelopmental disorder (NDD) is a rare autosomal-dominant disease with developmental delay and mild to severe intellectual disability. So far, fewer than 30 affected individuals with mostly recurrent, de novo missense variants in PPP2R5D were reported. Recently, parkinsonism with an onset between 20 and 40 years was reported in four adult individuals with the same p.(Glu200Lys) variant in PPP2R5D. By trio exome sequencing we now identified the variant p.(Glu198Lys) in a 29 year old woman presenting with typical clinical manifestations of PPP2R5D-related neurodevelopmental disorder and additionally with motor decline and levodopa responsive, early-onset parkinsonism from her mid-twenties on. Accordingly, a clear reduction of dopamine transporter in the striatum on both sides was revealed by brain scintigraphy. Our findings further expand the molecular and clinical spectrum of PPP2R5D-related NDD and confirm the association with parkinsonism in early adulthood. This has marked implications for prognosis of PPP2R5D-related NDDs and for the therapeutic management of motor decline and parkinson-like symptoms in affected individuals.
['Hetzelt|Katalin L M L|KLML|', 'Kerling|Frank|F|', 'Kraus|Cornelia|C|', 'Rauch|Christophe|C|', 'Thiel|Christian T|CT|', 'Winterholler|Martin|M|', 'Reis|André|A|', 'Zweier|Christiane|C|']
D017668:Age of Onset D000978:Antiparkinson Agents D003342:Corpus Striatum D005260:Female D006801:Humans D007980:Levodopa D020125:Mutation, Missense D020734:Parkinsonian Disorders D010641:Phenotype D054648:Protein Phosphatase 2 D055815:Young Adult
Parkinsonism Neurodevelopmental disorder PPP2R5D Parkinson's disease