2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Biallelic Variations in ATP13A2 Manifesting with a Complicated Motor Neuron Disease Phenotype

Pdf Summary

This case report discusses a 19-year-old female patient who presented with neuromuscular disease symptoms and was eventually diagnosed with biallelic pathogenic variants in the ATP13A2 gene. The patient's symptoms included muscular weakness, muscle spasms, blurry vision, bladder incontinence, breathing difficulties, swallowing difficulties, and excessive salivation. Genetic testing revealed a pathogenic variant in the ATP13A2 gene, as well as variants of uncertain significance in other genes. The patient's diagnostic assessments, including brain and cervical spine MRI, EMG conduction studies, and modified barium swallow, were normal. The patient was started on carbidopa-levodopa therapy and atropine drops for symptom management. Physical therapy and speech therapy were also recommended for muscle strength and dysarthria improvement, respectively. The patient was advised to start non-invasive ventilation at home for breathing difficulties. <br /><br />A literature review found that biallelic mutations in ATP13A2 are present in rare neurodegenerative diseases such as Kufor-Rakeb syndrome and Hereditary Spastic Paraplegia. The patient's symptoms were compared to previous clinical descriptions in the literature, which were characterized by cognitive delay, various motor system disturbances, and neuroimaging or neuromuscular findings. The patient's time to diagnosis was 18 years, which was longer than the average time to diagnosis reported in previous studies. The patient's symptoms and features were unique compared to other cases described in the literature.<br /><br />In conclusion, biallelic variations in the ATP13A2 gene are associated with a rare form of neurodegenerative disease characterized by upper and lower motor neuron disease, hearing loss, cognitive-behavioral abnormalities, and extrapyramidal features. The case highlights the importance of considering genetic disorders with neurologic presentations and the need for early diagnosis and intervention.

Asset Subtitle

Co-Author - Maria Bederson, MS; Co-Author - Dhruv Patel, BS; Presenting Author - Jacquelyn Johnson, MS, CGC; Co-Author - Robert Bucelli, MD, PhD; Co-Author - Christina Laukaitis, MD, PhD;

Meta Tag

Brain/Nervous System

Clinical History

Genome sequencing

Genotype-Phenotype Correlations

Identification of Disease Genes

Neuroscience

Phenotype

Phenotypic delineation of disorders

Respiratory System

Sequencing

Variant Detection

Co-Author Maria Bederson, MS

Co-Author Dhruv Patel, BS

Co-Author Robert Bucelli, MD, PhD

Co-Author Christina Laukaitis, MD, PhD

Presenting Author Jacquelyn Johnson, MS, CGC

Keywords

neuromuscular disease

ATP13A2 gene

biallelic pathogenic variants

muscular weakness

muscle spasms

blurry vision

bladder incontinence

breathing difficulties

swallowing difficulties

excessive salivation