Date of Release: May 2, 2022
Expiration Date: April 30, 2024
Credits offered: CME, P.A.C.E.®,
Estimated time for completion: 4.5 hours
Course must be completed by the expiration date
The episodic movement disorder phenotype often leads to diagnostic odysseys that end with the medical geneticist. In current practice, diagnosis is very late and patients with episodic movement disorders may reach the geneticist at any age. Despite a yield of 17%- 50% in confirmed neurogenetic diagnoses among patients with childhood-onset movement disorders in general, the average time to diagnosis was 11 years after symptom onset [PMID 30363430, 30283815]. A geneticist familiar with genetic causes of this phenotype can substantially improve patients’ care by making a timely diagnosis.
This practical, case-based session will broaden participants’ knowledge of neurogenetics by introducing key genetic and metabolic causes of episodic movement disorders beyond acute intoxication, as well as their implications for testing, prognosis, and treatment. At the end of the session, participants will be able to narrow the differential diagnosis of a patient with episodic movement disorder, select appropriate testing panels, and understand potential treatments.
An expert panel of neurogeneticists will present clinical cases, each followed by discussion of the patient’s condition and management. The disorders were selected to provide a broad overview of the diversity of movement disorder-associated genes:
- ADCY5-related Dyskinesias (20 min): This gain-of-function disorder can involve paroxysmal chorea, dystonia, or myoclonus which can continue through the night, unlike most movement disorders. The presenter will be Dr. Fuki Hisama, the author of the GeneReview for this condition.
- SLC2A1-related movement disorders / GLUT1 deficiency syndrome (G1D) (20 min): The spectrum of neurological involvement includes exercise-induced dystonia and other non-epileptic movement disorders, which can present in adults. Cerebral energy deficiency can be directly treated using the ketogenic diet. The presenter will be Dr. Juan Pascual, the author of the GeneReview for this condition.
- Alternating hemiplegia of childhood (AHC) (20 min): This disorder caused due to pathogenic ATP1A3 variants is characterized by distinctive clinical features such as monocular nystagmus. Management of respiratory compromise during episodes of paralysis is important, as well as treatment of co-occurring epilepsy and potential use of flunarizine. The presenter will be Dr. Sho Yano, who has described atypical ATP1A3-associated phenotypes and conducts research on AHC.
- Neurometabolic Disorders with Episodic Movement Disorder Phenotypes (25 min): Pyruvate dehydrogenase complex deficiency and TANGO2-related recurrent metabolic crises with encephalomyopathy and cardiac arrhythmias can both present with intermittent movement disorders. Biochemical testing and/or the presence of metabolic crises can help reach the diagnosis but may not always occur during the initial few years with atypical phenotypes. The presenter will be Dr. Kuntal Sen, who has described the intermittent movement disorders in these conditions and conducts research on mitochondrial disorders [PMID 30650451, 33592356].
Target Audience:
Clinical Genetics
Learning Objectives:
At the conclusion of this session, participants should be able to:
- Describe the phenomenology of movement disorders
- Discuss the basic classification of pediatric movement disorders.
- ADCY5 related Dyskinesia: Identify clinical features that could suggest the diagnosis of ADCY5-related dyskinesia.
- GLUT1DS: Identify the phenomenology and assess whether treatment is needed for the movement events typical of Glucose transporter type I deficiency.
- GLUT1DS: Discuss the clinical heterogeneity of GLUT-1 related disorders.
- Alternating hemiplegia: Recognize the classic childhood-onset presentation of alternating hemiplegia as well as adult-onset rapid-onset dystonia-parkinsonism and variant phenotypes.
- Analyze other phenotypes associated with ATP1A3 including adult-onset rapid-onset dystonia-parkinsonism and cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss.
- Compare biochemical and clinical features of metabolic disorders to those of other causes of intermittent movement disorders.
- Discuss a diagnostic approach for suspected inborn errors of metabolism presenting with movement disorders.