Parkinson’s disease with hypocalcaemia: adult presentation of 22q11.2 deletion syndrome

Abstract

A growing amount of evidence indicates that 22q11.2 deletion syndrome (22q11.2DS) increases the risk of early-onset Parkinson's disease (EOPD). Here, we describe a 36-year-old patient with EOPD. The patient presented with 22q11.2DS features, including associated cognitive disabilities, hypocalcaemia and facial dysmorphia that led us to screen for and confirm this deletion. In addition, hypocalcaemia and vitamin D deficiency were the main factors responsible for severe, painful muscle spasms that were non-levodopa (L-Dopa) responsive and remitted after calcium and vitamin D replacement therapy. Many patients with this deletion remain undiagnosed until adulthood due to the absence of 'major' phenotypic hallmarks, which usually present during early childhood. Later onset problems involving various medical subspecialties are increasingly recognised as important components of 22q11.2DS. Therefore, the multisystem nature and associated burden of morbidities demand a high degree of suspicion for this entity from all clinicians regardless of their medical subspecialty.

22q11.2 Deletion Syndrome–Associated Parkinson's Disease

“…However, PD in 22q11.2DS may be difficult to diagnose as a result of the clinically complex multisystem nature of the condition with lack of familiarity with the syndrome, even compared to rarer conditions . For example, Wilson's disease was considered, but not confirmed, in at least 4 reported patients with 22q11.2DS and abnormal movements . Use of antipsychotic medications may delay the diagnosis of PD significantly, given that parkinsonism may be assumed to be drug induced .…”

“…6 For example, Wilson's disease was considered, but not confirmed, in at least 4 reported patients with 22q11.2DS and abnormal movements. [28][29][30][31] Use of antipsychotic medications may delay the diagnosis of PD significantly, given that parkinsonism may be assumed to be drug induced. 23 Other medications that may be associated with parkinsonism, including selective serotonin reuptake inhibitors, 32 are also frequently taken by individuals with 22q11.2DS.…”

“…23 22q11.2DS-specific management considerations necessitate a multidisciplinary approach. 26 Prevalent comorbid conditions in 22q11.2DS that may affect PD expression and/or treatment outcome include, but are not limited to, recurrent seizures, 16 the possible association between 22q11.2DS and other movement disorders (e.g., myoclonic disorders), 9,[11][12][13] psychiatric disorders, 8 intellectual disability, 26 sensory dysfunction, 5,9,10,19 endocrinological disorders (i.e., thyroid dysfunction, hypoparathyroidism, hypocalcemia, and hypomagnesemia), 5,20,30 and obstructive sleep apnea. 22 In the case of planned treatment with clozapine, 38 which has proven efficacy for schizophrenia in 22q11.2DS, 39 prophylactic anticonvulsant treatment is recommended given the lowered seizure threshold.…”