New insights into genetic profiles of movement disorders linked to mitochondrial diseases

Movement disorders (MDs) associated with mitochondrial cytopathies (MCs) exhibit a broad and complex range of symptoms, making diagnosis challenging, according to a poster presented at the 2024 International Congress of Parkinson’s Disease and Movement. Early onset and specific brain MRI findings are key predictors for identifying genetic mutations, though genetic confirmation is not always possible.

A retrospective chart review was conducted on 76 cases of clinically suspected MCs. The study utilized whole exome sequencing (WES) to explore the genetic profile of these patients.

Among the 76 identified cases, the median age at onset (AAO) was 10 years, with a range spanning from 1 month to 45 years. Movement disorders (MDs) were present in 49 patients (65.3%), with a median AAO of 12 years. The types of MDs observed included ataxia (65.3%), dystonia (36.7%), tremors (20.4%), recurrent falls (18.4%), parkinsonism (16.3%), myoclonus (16.3%), and chorea (8.2%). Systemic symptoms commonly associated with these patients included seizures (28.6%), neuropathy (22.4%), hearing loss (22.4%), and optic atrophy (18.4%).

Genetic diagnoses were achieved in 16% of the overall cases and 16.3% of those with MDs. The most common genetic findings were mitochondrial complex deficiencies, Leigh spectrum, and pyruvate dehydrogenase deficiency. Predictors for genetic positivity included an age at onset of less than 10 years and brain MRI results suggestive of mitochondrial involvement.

Reference
Dhar VD, et al. Utility of Whole Exome Sequencing in movement disorders potentially related to Mitochondrial cytopathies [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/utility-of-whole-exome-sequencing-in-movement-disorders-potentially-related-to-mitochondrial-cytopathies/. Accessed September 27, 2024.