Objective: Report a case of early-onset Parkinson Disease with hypocalcemia and mild dysmorphic features leading to diagnosis of 22q11.2 deletion syndrome

Background: The 22q11.2 Deletion Syndrome is the most frequent human deletion syndrome affecting at least 1 in 4000 live births. The phenotypic spectrum is broad, crossing all medical specialities and can present at different age groups. Despite still being underdiagnosed, there is a recent growing evidence for the association with Early-Onset Parkinson Disease.

Methods: Case Report

Results: A 36-year-old right handed man at age 31 first noticed difficulties with fine motor control and a right-hand rest tremor. Two years later he was diagnosed with PD and had improvement with levodopa initiation. At age 35 there was a spread of parkinsonian symptoms involving his left-body with periods of painful hemidystonic posturing lasting seconds to a few minutes, occurring many times per day and precipitated by exertion and anxiety. After  increasing doses of dopaminergic therapy he sought emergency department presenting peak-dose dyskinesias, akathisia and rhabdomyolysis. Laboratory analysis revealed in addition to CK increase an hypocalcemia. After correcting metabolic problems the dopaminergic therapy was adjusted for lower daily doses and he started chronic calcium replacement therapy with a great improvement in the hemidystonic/espamodic posturing. He had a normal brain MRI and a DaTSCAN revealing severe bilateral decreased striatal dopamine transporter uptake. The presence of hypocalcemia and PD associated with slight facial dysmorphic features characteristic of DiGeorge syndrome led to the screening of 22q11.2 deletion. An MLPA (Multiplex Ligation-dependent Probe Amplification) testing confirmed the deletion.

His past medical history was unremarkable, except for mild developmental delay. There was no consanguinity or family history of Parkinsonism.

Conclusions: Adults with milder manifestations of 22q11.2 Deletion Syndrome remain unrecognized and pose a diagnostic challenge. In our case hypocalcemia in the presence of mild but characteristic dysmorphic features lead to the diagnosis of this syndrome. Furthermore, the identification and attempted treatment of hypocalcemia, that can by itself aggravate tremors or induce spasmodic muscular contractions, can avoid erroneous changes in dopaminergic replacement therapy as well as prevent other devastating medical consequences.

References:

1. Mok KY, Sheerin U, et al. Deletions at 22q11.2 in idiopathic Parkinson’s disease: a combined analysis of genome-wide association data. Lancet Neurol 2016; 15: 585–96.
2. Butcher NJ, Kiehl T-R, Hazrati L-N, et al. Association between early-onset Parkinson disease and 22q11.2 deletion syndrome: identification of a novel genetic form of Parkinson disease and its clinical implications. JAMA Neurol 2013; 70: 1359–66.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-onset-parkinson-disease-with-hypocalcemia-adult-presentation-of-22q11-2-deletion-syndrome/