Clinical Report: Neurodevelopmental Decline in PLA2G6-Related Neurodegeneration

Background

Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive neurodegenerative disorder characterized by early psychomotor regression and progressive motor impairment. It is part of the PLA2G6-associated neurodegeneration spectrum, which can present with normal neuroimaging findings, complicating diagnosis.

Data Highlights

No numerical data or trial data available in the article.

Key Findings

• The patient exhibited progressive neurodevelopmental regression starting at 18 months of age.
• Normal brain MRI findings were observed despite significant neurological impairment.
• A homozygous PLA2G6 variant was identified through whole-exome sequencing.
• Clinical manifestations included loss of motor abilities, absence of verbal language, and marked hypotonia.
• Normal neuroimaging does not exclude PLA2G6-associated neurodegeneration, particularly in atypical cases.

Clinical Implications

This case underscores the necessity of considering genetic testing in pediatric patients with neurodevelopmental regression, even when neuroimaging appears normal. Clinicians should be aware that PLA2G6-associated neurodegeneration can present atypically, necessitating a high index of suspicion.

Conclusion

The findings highlight the critical role of molecular diagnostics in identifying PLA2G6-associated neurodegeneration, even in the absence of typical neuroimaging abnormalities. Early diagnosis can facilitate appropriate management and support for affected families.

Related Resources & Content

1. Consensus Clinical Management Guideline for PLA2G6-Associated Neurodegeneration (PLAN), 2026 -- Clinical management guidelines
2. PLA2G6-Associated Neurodegeneration - GeneReviews® - NCBI Bookshelf, 2026 -- GeneReviews on PLA2G6
3. Acta Neuropathologica — Exploring the Connection Between G51D SNCA Mutation and α-Synucleinopathy: Implications for Parkinson's Disease and Multiple System Atrophy
4. European Radiology — Utilizing Brain MRI and FDG-PET for Diagnosing Neurodegenerative Disorders
5. Acta Neuropathologica — Extensive Presence of Alpha-Synuclein Oligomers in Brains Affected by Multiple System Atrophy Revealed Through Proximity Ligation
6. Brain — GGC Repeat Expansions in NOTCH2NLC Induce uN2CpolyG Protein Formation Linked to Cerebral Amyloid Angiopathy
7. Consensus Clinical Management Guideline for PLA2G6-Associated Neurodegeneration (PLAN)
8. PLA2G6-Associated Neurodegeneration - GeneReviews® - NCBI Bookshelf