Neurodevelopmental disorder and Early Onset Parkinson’s disease in 22q11.2 Deletion Syndrome

Introduction Early Onset Parkinson’s disease (EOPD) refers to parkinsonism occurring within 21 and 50 years of age. Twenty to 30% of EOPD cases are related to monogenic alterations, with a lower age of onset indicating a higher the risk of an underlying a genetic cause. Methods We report on a 40-year-old woman with a neurodevelopmental disorder and an EOPD. The diagnostic work-up included a neurophysiological analysis of her movement disorders, brain MRI and DaT-Scan, and Genetic Analysis. Results The patient suffered from developmental delay and mild intellectual disability. At the age of 40, she was diagnosed with psychiatric disorders (anxiety, apathy and anhedonia). No pharmacological treatment was prescribed. A few months later, she experienced progressive hypokinesia. Neurological examination showed hypomimia, asymmetrical bradykinesia (left>right), limb stiffness and reduced arm swing, resting tremor of the left hand and chin, and postural tremor of upper and lower limbs. Neurophysiological examination revealed a regular 6 Hz frequency of rest chin and left-hand tremor and a further 10 Hz postural tremor of the left hand. Levodopa/carbidopa administration notably improved bradykinesia and resting tremor while not affecting postural tremor. Brain MRI was normal. A DAT scan detected reduced radiotracer uptake in the right striatum and left putamen. CGH-Array revealed a 2.4 Mb 22q11.21 microdeletion associated with DiGeorge syndrome. Comment and Conclusions 22q11.2 deletion syndrome (22q11.2DS) can manifest with neurological and psychiatric symptoms as initial presentation. EOPD presents in 22q11.2DS with bradykinesia, stiffness/rigidity, reduced arm swing, and asymmetric tremor. Severe psychiatric disorders may anticipate the emergence of EOPD. The progression of the motor disorder, as well as neuroimaging exploration, are compatible with the diagnosis of idiopathic PD. COMT gene, which codifies for the catechol-O-methyltransferase enzyme implied in peri synaptic astrocyte dopamine catabolism, is located in the classical 22q11.2 deletion region. Hyperdopaminergic autotoxicity secondary to COMT defect has been hypothesised as a cause of PD in this syndrome.