Concomitant Facioscapulohumeral Muscular Dystrophy and Parkinsonism Mimicking Multiple System Atrophy

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Video 1

Segment 1: The subject is examined at age 65. She displays asymmetric leg weakness, steppage, and marked stooped posture. Her posture improves upon grabbing the walker. We can also appreciate freezing of gait and typical FSHD1 features such as scapular winging and a trapezius hump. Segment 2 was recorded at age 68 and displays camptocormia. Bell's phenomenon, another typical feature of FSHD, is also evident as well as irreducible anterocollis, right laterocollis, hypomimia, marked left-side bradykinesia, posturing of the fingers, and mild postural tremor. Alternating hand movements are slow and irregular. We can also see reduced foot stamps, loss of left dorsal flexion, reduced right dorsal flexion, and resting tremor of the right foot.

Martin Paucar MD, Stanislav Beniaminov MD, Göran Solders MD, PhD and Per Svenningsson MD, PhD

Article first published online:  20 OCT 2015 | DOI: 10.1002/mdc3.12247


Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disease with an estimated prevalence of 5 cases per 100,000 individuals.[1-3] Two forms of this disease are recognized: FSHD1, which constitutes the majority of cases (95%), is caused by contractions of the D4Z4 allele in chromosome 4q35, and FSHD2 (5%), which is caused by mutations in SMCHD1 located in chromosome 18p. The normal D4Z4 allele spans between 11 and 100 repeat units whereas FSHD1 subjects have between 1 and 10 repeat units in this allele.[2] Symptoms in FSHD1 are very variable; onset is in the first or second decade of life with weakness and atrophy in facial and scapula-stabilizer muscles. Extramuscular manifestations often include hearing loss and, more seldom, retinal abnormalities.[1, 2] An association between FSHD1 and a movement disorder has been reported only once in a subject with cervical dystonia.[4] We report here on a subject affected by FSHD1, dystonia, and levodopa responsive parkinsonism.

Case Report

The subject is a 68-year-old Swedish woman with a family history of FSHD (Fig. 1). Her past medical history consists of hypertonia and lumbal spinal stenosis, which was managed conservatively. At the age of 53, she developed progressive weakness of the neck, shoulders, arms, and facial muscles. She displayed typical FSHD features, namely, Bell's phenomenon, upward rotation of the shoulder blades causing scapular winging, and leg weakness (see Video 1). The latter was likely exacerbated by spinal stenosis. MRI of the spinal cord revealed fat infiltration of paraspinal muscles. Electromyography (EMG) revealed widespread myopathic abnormalities and signs of a lumbosacral radiculopathy. A study of peripheral nerve conduction was normal. A hearing test revealed a mild high-tone loss, but the subject did not require hearing aids. Examination of the retina was normal.

A targeted mutation analysis revealed four repeat units in the contracted D4Z4 allele in chromosome 4q35. At the age of 63, the subject noticed insidious resting tremor predominately on the left side, back pain, stiffness, and walking difficulties with freezing of gait. Two years later, bradykinesia, mild rigidity, hypomimia, marked stooped posture, irreducible anterocollis, and marked right laterocollis were found upon examination (see Video 1).There was no “geste antagoniste” in this case. The subject also reported anosmia, benign visual hallucinations, and rapid eye movement sleep behavior disorder. Her University of Pennsylvania Smell Identification Test score was 11, compatible with pronounced anosmia. Screening with Montreal Cognitive Assessment yielded 25 points, and a psychometric evaluation demonstrated visuospatial deficits. Neither dysautonomia nor fluctuacting cognition were found. Brain MRI at the age of 66 was normal, but dopamine transporter imaging revealed significantly reduced nigrostriatal uptake (Fig. 2). Her tremor receded to treatment with l-dopa (current dosage 100 mg q.i.d.); ropinirol (4 mg o.i.d) was added later. Camptocormia appeared later in the course of disease and the subject became unable to walk without support. The frequency of her visual hallucinations was reduced after introducing quetiapine. A recent second EMG displayed a tonic and phasic pattern in both sternocleidomastoid muscles, more pronounced in the left side, and right splenius capiti muscle besides myopathic features. The latter were also present in paraspinal muscles. The use of botulinum toxin in her cervical muscles was refrained from owing to the marked myopathic abnormalities.

Legend to Pedigree

Figure 1. Legend to pedigree of an FSHD1 family whose index case is indicated by the arrow. The subject could not recall other cases of parkinsonism in her family.





Dopamine Transporter Imaging

Figure 2. Dopamine transporter imaging displaying asymmetric and significantly reduced nigrostriatal uptake in a subject affected by FSHD1.




Whether the occurrence of l-dopa responsive parkinsonism is coincidental in this case or an underdiagnosed feature of FSHD1 remains to be determined. In rare cases with large contractions of the D4Z4 allele, learning difficulties and epilepsy have been reported.[5] The presence of anterocollis and parkinsonism in our case are reminiscent of MSA; however, concomitant widespread myopathy, absence of dysautonomia, and disease duration argue against this disease. This presentation is rather compatible with idiopathic Parkinson's disease. Diagnosing movement disorders in individuals affected by neuromuscular diseases can be challenging. The predominant muscle weakness of FSHD may initially overshadow the presence of a movement disorder. Camptocormia in FSHD has been mistaken for dystonia in the past.[6] Camptocormia in this case is likely due to myopathic weakness whereas abnormal neck posture is likely to be the result of both dystonia and the underlying myopathy. Other neuromuscular diseases such as the multisystem TDP43 proteinopathies display protean manifestations that include parkinsonism.[7] However, in FSHD1, there is no evidence of protein aggregation in the muscle or in the brain. The unique mechanism of disease proposed for FSHD1 states that a defective repression of the D4Z4 macrosatellite repeat array leads to expression of the DUX4 retrogene in skeletal muscle.[3, 8, 9] It is still unknown whether this expression also occurs in the brain. Of note, TUBB7P located near the contracted chromosome 4q35 region was one of the first candidate genes for FSHD. Given that its product has been reported to interact with parkin, one could speculate about an altered interaction as a potential link between the myopathy and the extrapyramidal involvement.[10] Despite the likely coincidental character of the described movement disorders and FSHD in the cases reported so far, we call for clinicians’ attention on this rare combination, which may contribute to expand the increasingly broad spectrum of FSHD in the future.

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