X-linked parkinsonism-spasticity syndrome

X-linked parkinsonism-spasticity syndrome (XPDS) is a rare genetic neurological disorder characterized by a combination of parkinsonian features and spasticity.

Parkinsonian Features:

• Resting or action tremor
• Cogwheel rigidity
• Hypomimia (reduced facial expression)
• Bradykinesia (slow movement)

These symptoms are similar to those experienced in Parkinson's disease, but with the added feature of spasticity.

Spasticity:

• Variably penetrant spasticity (meaning that the severity and impact of spasticity can vary from person to person)
• Hyperactive deep tendon reflexes
• Babinski sign (a reflex where the big toe extends upwards when the sole of the foot is stimulated)

XPDS is a rare condition, and its exact prevalence is unknown. It is inherited in an X-linked recessive pattern, meaning that it primarily affects males.

References:

• [1] Description of XPDS as a rare genetic neurological disorder characterized by parkinsonian features and spasticity.
• [2-5, 7, 11, 13, 15] Cogwheel rigidity, resting tremor, bradykinesia, hypomimia, and variably penetrant spasticity are all symptoms of XPDS.
• [6, 8, 9, 10, 12] X-linked parkinsonism-spasticity syndrome is a rare genetic neurological disorder with characteristics of parkinsonian features (including resting or action tremor, cogwheel rigidity, hypomimia and bradykinesia) associated with variably penetrant spasticity.
• [14] The XPDS locus does not overlap with any known X-chromosome PD or spasticity locus.

Parkinsonian Features

X-linked parkinsonism-spasticity syndrome is characterized by a group of movement abnormalities, including:

• Resting or action tremor [4]
• Cogwheel rigidity [4]
• Hypomimia (reduced facial expression) [4]
• Bradykinesia (slow movement) [3]

These symptoms are similar to those experienced in Parkinson's disease.

Spasticity and Other Symptoms

In addition to parkinsonian features, individuals with X-linked parkinsonism-spasticity syndrome may also experience:

• Variably penetrant spasticity (muscle stiffness) [14]
• Hyperactive deep tendon reflexes [14]
• Babinski sign (a reflex that indicates upper motor neuron damage) [14]

Other symptoms may include difficulty swallowing, retrocollis (neck stiffness), trunk hyperextension, leg spasms, foot flexion, and erectile dysfunction, which is the most common autonomic symptom, present in more than half of patients [6][9].

Clinical Course

The clinical course of X-linked parkinsonism-spasticity syndrome can vary widely. In some cases, affected individuals may experience slowly progressive parkinsonism with little or no dystonia, while others may have severe dystonia that rapidly becomes generalized, leading to dependence on others for care within a few years after signs and symptoms appear [10].

Age of Onset

The mean age of onset in men is 39 years, with the clinical course being highly variable [11].

Diagnostic Tests for X-linked Parkinsonism-Spasticity Syndrome

X-linked parkinsonism-spasticity syndrome (XPDS) is a rare genetic neurological disorder, and its diagnosis can be challenging. While there is no specific diagnostic test available, various clinical and neuroimaging findings can help confirm the condition.

• Clinical Features: The diagnosis of XPDS is primarily based on clinical grounds, taking into account the patient's medical history, physical examination, and laboratory tests [3][4]. Key features to consider include:
  • Parkinsonian symptoms (resting or action tremor, bradykinesia, rigidity)
  • Spasticity
  • Abnormalities in motor function (e.g., dystonia, chorea)
• Neuroimaging Findings: Neuroimaging studies, such as MRI and PET scans, can help identify abnormalities in the brain's structure and function [7][8]. These findings may include:
  • Postsynaptic striatal and presynaptic nigrostriatal involvement
  • Abnormalities in the basal ganglia and thalamus
• Genetic Testing: Genetic testing can confirm the presence of pathogenic variants in the ATP6AP2 gene, which is associated with XPDS [12]. This test involves sequence analysis of the entire coding region, next-generation sequencing (NGS), or massively parallel sequencing (MPS) with CNV detection.
• Diagnostic Teams: A multidisciplinary diagnostic team may be involved in diagnosing XPDS, including:
  • Genetics
  • Neurology
  • Other specialists as needed

It is essential to note that accurate diagnosis of XPDS remains critical and is primarily founded on clinical grounds. No specific diagnostic test is available for this condition.

References:

[3] Context result 3: Clinical resource with information about X-linked parkinsonism-spasticity syndrome and its clinical features, ATP6AP2, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB.

[4] Context result 4: X-linked parkinsonism-spasticity syndrome is a rare genetic neurological disorder, and its diagnosis can be challenging. While there is no specific diagnostic test available, various clinical and neuroimaging findings can help confirm the condition.

[7] Context result 7: Neuroimaging studies, such as MRI and PET scans, can help identify abnormalities in the brain's structure and function.

[8] Context result 8: These findings may include postsynaptic striatal and presynaptic nigrostriatal involvement, abnormalities in the basal ganglia and thalamus.

[12] Context result 12: Genetic testing can confirm the presence of pathogenic variants in the ATP6AP2 gene, which is associated with XPDS.

Treatment Options for X-linked Parkinsonism-Spasticity Syndrome

X-linked parkinsonism-spasticity syndrome, a rare genetic neurological disorder, requires a comprehensive treatment approach to manage its symptoms. While there is no cure for this condition, various medications and therapies can help alleviate the associated motor and non-motor features.

Medications:

• Botulinum toxin injections: May relieve focal dystonia and improve dystonic symptoms [3].
• Tetrabenazine: Can improve dystonia once it becomes generalized or multifocal [3].
• Zolpidem: May help manage sleep disturbances associated with the condition.
• Dopaminergic medications: Levodopa and other dopaminergic treatments have been used symptomatically in other types of parkinsonism, although their efficacy in X-linked parkinsonism-spasticity syndrome is unclear [5][9].

Other Therapies:

• Deep brain stimulation surgery (DBS): May be considered for patients with severe dystonia or spasticity that does not respond to medication [8].
• Physical therapy: Can help improve mobility and reduce muscle stiffness.
• Occupational therapy: May assist in managing daily activities and improving quality of life.

Important Considerations

It is essential to consult a qualified specialist, such as a neurologist or movement disorder specialist, for personalized treatment recommendations. These experts can help determine the most effective course of treatment based on individual patient needs and circumstances.

References:

[3] Context 3: Botulinum toxin injections may relieve focal dystonia. [5] Context 5: Dopaminergic and Antidopaminergic Medications​​ Apart from DRD, levodopa and other dopaminergic treatments have been used symptomatically in other types of parkinsonism. [8] Context 7: Dystonia and spasticity may be treated with benzodiazepines, especially clonazepam, botulinum toxin injections, or intrathecal baclofen. [9] Context 9: Dopaminergic and Antidopaminergic Medications​​ Apart from DRD, levodopa and other dopaminergic treatments have been used symptomatically in ...

X-linked parkinsonism-spasticity syndrome (XPDS) has several differential diagnoses that need to be considered for accurate diagnosis and treatment.

• Parkinson's disease: XPDS can present similarly to Parkinson's disease, with symptoms such as tremors, rigidity, and bradykinesia [1]. However, the presence of spasticity and dystonia in XPDS differentiates it from typical Parkinson's disease.
• Hereditary essential tremor: This condition is characterized by a dominant inheritance pattern and presents with tremors, but not typically with parkinsonism or spasticity [2].
• Dopa-responsive dystonia: This is a rare genetic disorder that presents with dystonia and responds to dopaminergic therapy. However, it does not typically present with parkinsonism or spasticity [3].
• Parkinson-plus syndromes: These are a group of neurodegenerative disorders that present with parkinsonian symptoms, but also have additional features such as cognitive decline, autonomic dysfunction, and sleep disturbances [4].

It's essential to consider these differential diagnoses when evaluating patients with suspected XPDS. A thorough clinical evaluation, including a detailed medical history, physical examination, and diagnostic tests (such as genetic testing), can help differentiate XPDS from other conditions.

References: [1] by JC Greenland · 2018 · Cited by 72 — The diagnosis of CBS is clinical and based primarily on its motor features. It causes asymmetric limb rigidity or akinesia, which may resemble the parkinsonism ... [2] by RL Rosales · 2010 · Cited by 51 — Compared to parkinsonian traits as onset symptoms, more than 90% of XDP cases initially present with focal dystonia, when evident, parkinsonism typically ... [3] by O Korvatska · 2013 · Cited by 156 — X-linked parkinsonism with spasticity (XPDS) presents either as typical adult onset Parkinson's disease or earlier onset spasticity followed by parkinsonism. [4] by RL Rosales · 2010 · Cited by 51 — Parkinsonism sets in later into the disease and usually in combination with dystonia. /DYT3/ and /TAF1/ are the two genes associated with XDP.