Patient's neurological examination showed continuous, patternless, involuntary hyperkinetic movements focally involving the first three digits of the left hand, which were not distractible or entrainable nor associated with an urge to perform the movements. The observed phenomenology was consistent with chorea, which was present at rest, on posture, and while walking and could only be abolished by sleep. Bradykinesia was not detectable on finger tapping whereas mild myoclonic jerks were present at the same site (see Video 1). No involuntary movements were observed in the left foot. Chorea had been present since age 53, with a gradual onset and no spreading or worsening and did not cause major functional limitations to the patient. A CT brain scan showed extensive bilateral basal ganglia and dentate nuclei calcifications, consistent with FD (Fig. 1A,B). A brain MRI demonstrated a hyperintense focal lesion on diffusion-weighted imaging sequences in the periventricular white matter of the left frontal lobe, consistent with a recent lacunar stroke (Fig. 1C,D). Blood calcium, phosphates, vitamin D, and parathyroid hormone were all in the normal range. Blood glocose was within normal limits on admission (95 mg/dL). Despite the unusual presentation, rarer genetic or autoimmune causes of chorea, such as Huntington's disease and antiphospholipid syndrome, were not investigated in view of the absence of family history, normal cognition (Mini–Mental State Examination: 29/30), duration and lack of spreading of the movement disorder (that had been present for the past 12 years), and the patient's age and multiple cardiovascular risk factors.
Figure 1. (A and B) Patient's brain CT scan at age 65, showing extensive bilateral calcification of basal ganglia and dentate nuclei in the cerebellum. (C and D) Patient's brain MRI on admission, demonstrating a left frontal lacunar stroke in the periventricular white matter.
Genetic analysis revealed a missense mutation in the SLC20A2 gene (c.338C>G), which creates a premature stop codon in the coding protein (p.Ser113*), and was previously reported in association with an atypical parkinsonian phenotype. Other family members were not available for genetic testing.
Isolated hyperkinetic movement disorders have only rarely been described as a manifestation of FD since the identification of the first three causative genes. Nicolas et al. found 10 SLC20A2-positive patients, of whom 1 had dystonia and 1 orofacial dyskinesias. Among 15 PDGFRB-positive subjects, only 1 was reported to have chorea, but no details on the distribution of movement disorders were available. Interestingly, also, paroxysmal dystonia has been reported in FD with and without SLC20A2 mutations.[6-8]
Recently published genetic screenings demonstrated poor correlation between the site and extension of brain calcifications and clinical symptoms in FD, with patients showing no or minor abnormalities on examination despite extensive calcium deposition. Here, we report on an unusual clinical phenotype of FD, with adult-onset focal unilateral chorea despite extensive bilateral calcifications in the striatum and dentate nuclei. This case confirms the clinical heterogeneity of FD, broadening the spectrum of hyperkinetic movement disorders associated with SLC20A2 mutations. To the best of our knowledge, a similar phenotype has not been previously reported on in SLC20A2-positive patients.