Isolated limb dystonia as presenting feature of Parkin disease

Mutations in the parkin gene (PRKN, PARK2) cause autosomal-recessive early-onset Parkinson's disease (PD). Reported parkin mutation frequencies vary across studies, but percentages up to 49% of familial and 20% of sporadic cases of early-onset PD have been reported on. [1][2][3][4] It is difficult to clinically distinguish parkin mutations from other causes of PD. Clinical clues for mutations in the parkin gene are symmetrical onset, dystonia, hyperreflexia, slower disease progression, and a good response to levodopa. In this report, we describe a 35-year-old Dutch man with "foot drop dystonia" resulting from a parkin mutation. Case DescriptionThe patient was referred to our neurology outpatient clinic with a gait disorder. He had progressive difficulties with walking for 6 years. He complained of walking bent over with his legs apart. While walking, it felt like his feet dropped to the floor. His complaints worsened during the day and during exercise. In the beginning, he only experienced this during strenuous effort, especially while playing football. He ran straddle-legged on the lateral sides of his feet. He recovered in half an hour. At the end, playing football was not possible anymore. He also experienced trembling in his legs during walking and worsening with emotions and exhaustion. His girlfriend noticed a mumbled speech. He reported a restless sleep with flailing and kicking during sleep. Family history was negative for neurological or psychiatric disorders. There was no parental consanguinity. He has one healthy sister and no brothers or children.Neurological examination on admission showed a monotonous voice, minimal hypomimia, mild general rigidity, and minimal bradykinesia during finger tapping. He walked with exaggerated lifting and subsequently dropping of the feet, slightly with the legs apart, which we classified as a dystonic gait (see Video 1). Dopa-responsive dystonia (DRD) was in our differential diagnosis, because of worsening during the day and the combination of foot dystonia with some bradykinesia.5 Importantly, mild parkinsonism may occur in DRD. 6 Indeed, L-dopa/carbidopa 100/25 mg three times daily appeared successful. Brain MRI showed no abnormalities. Cerebrospinal fluid (CSF) analysis showed normal concentrations of biopterin, neopterin, and homovanillic acid (however, during L-dopa treatment). Genetic tests for mutations in the genes for guanosin triphosphate cyclohydrolase 1 (GCH1, DYT5), sepiapterin reductase (SPR), and tyrosin hydroxylase (TH) were negative. A dopamine transporter imaging with single-photon emission computed tomography (DAT SPECT) scan showed bilateral and asymmetrical loss of striatal DAT binding with the right striatum showing the largest loss (Figure 1). Finally, multiplex litigation-dependent probe amplification showed a compound heterozygous parkin mutation (i.e., deletion exons 3-6 and deletion exon 3).To prevent early development of L-dopa-induced dyskinesia, which is more common in patients with parkin mutations, 4 L-dopa/carbidopa was replaced by pram...

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“…For this, nuclear imaging (e.g., DAT SPECT) may be helpful. These PD patients, as with our case, may show a mutation in the parkin gene …”

Section: Discussionsupporting

confidence: 75%

Foot Drop Dystonia Resulting from parkin (PARK2) Mutation

Schipper

Munts

2015

Movement Disord Clin Pract

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“…The pathological process is usually restricted to the brainstem, and Lewy bodies are rarely found. Lower limb dystonia is increasingly recognized as a peculiar feature of parkin disease that may also occur as an isolated presenting feature …”

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confidence: 99%

Quantitative gait analysis in parkin disease: Possible role of dystonia

et al. 2016

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“…Isolated dystonia may be the presenting feature of combined syndromes that can remain isolated for a significant amount of time before another movement disorder appears. An isolated dystonia may be the long‐standing presenting feature of PARK2 parkinsonism (PARK‐Parkin) , of rapid‐onset dystonia parkinsonism (DYT12, DYT‐ATP1A3) , of Lubag disease (DYT3, DYT/PARK‐TAF1) and of dopa‐responsive dystonia (DYT5a, DYT‐GCH1 or DYT5b, DYT‐TH ). In most cases, a full‐house syndrome of combined dystonia will develop in time, whilst in some cases the phenotype will remain limited to isolated dystonia.…”

Section: Etiologymentioning

confidence: 99%

Dystonia: diagnosis and management

Albanese

Giovanni

Lalli

2018

Euro J of Neurology

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Clinical practice in dystonia has greatly evolved in recent years; a synthetic review on patient management is provided here. Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures or both. A recent classification has innovated clinical practice and serves as guidance for clinical assessment: Axis I describes clinical features, whereas Axis II indicates etiology. Dystonia presents with different syndromic aggregations with varied somatic involvement and some common features. There are five recognizable physical signs of dystonia: two main signs (dystonic postures and movements) and three additional signs (gestes antagonistes or tricks, mirror dystonia and overflow dystonia). There is still no validation of diagnostic criteria for the different dystonia syndromes, and many cases with mild phenomenology remain undiagnosed. Patients with dystonia also present non-motor features that are variably combined with the movement disorder. The features of the most common inherited and acquired dystonia syndromes are reviewed here. There is clear evidence of genetic-environmental interaction in the determinism of dystonia. The diagnostic process is guided by clinical examination and based on specific laboratory examinations. Symptomatic treatments are available for dystonia: botulinum neurotoxin injections are the primary choice for most focal dystonia syndromes; deep brain stimulation is useful in some generalized and non-generalized syndromes. Additional treatment strategies are currently being assessed.

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Isolated limb dystonia as presenting feature of Parkin disease

Cited by 25 publications

References 8 publications

Foot Drop Dystonia Resulting from parkin (PARK2) Mutation

Foot Drop Dystonia Resulting from parkin (PARK2) Mutation

Quantitative gait analysis in parkin disease: Possible role of dystonia

Dystonia: diagnosis and management

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