GENE: PLA2G6; INHERITANCE: Autosomal recessive; ONSET: Childhood; SYMPTOMS: Dystonia, ataxia, cognitive decline, and parkinsonism; NOTES: PLAN includes INAD, atypical NAD, and dystonia-parkinsonism; symptoms vary by subtype.
PLA2G6-Associated Neurodegeneration (PLAN) is one of the most common forms of NBIA, caused by changes (mutations) in the PLA2G6 gene. This gene provides instructions for making an enzyme that helps maintain healthy cell membranes. When it does not work correctly, nerve cells are damaged over time, leading to progressive movement, developmental, and cognitive challenges.
PLAN includes several overlapping conditions, each with different ages of onset and symptoms:
Infantile Neuroaxonal Dystrophy (INAD) – symptoms usually begin in infancy or early childhood.
Atypical Neuroaxonal Dystrophy (atypical NAD) – symptoms begin later, often between ages 4–20.
PLA2G6-related dystonia-parkinsonism – symptoms often appear in adolescence or adulthood.
Genetics & Mechanism
PLAN is caused by mutations in the PLA2G6 gene, which provides instructions for an enzyme called phospholipase A2 group VI. This enzyme is essential for maintaining the health of cell membranes in nerve cells.
Inheritance: PLAN is usually autosomal recessive. This means a child must inherit two non-working copies of the PLA2G6 gene (one from each parent) to develop the condition. Parents who each carry one faulty copy are typically healthy but have a 25% chance with each pregnancy of having an affected child.
Variants: Different mutations within the PLA2G6 gene account for the spectrum of PLAN presentations – from early-onset INAD to later-onset dystonia-parkinsonism.
Research: Ongoing studies suggest that not all genetic mechanisms behind PLAN are fully understood, and researchers continue to investigate how these gene changes cause the wide range of symptoms.
Symptoms
The symptoms of PLAN can vary widely depending on age of onset and form of the condition, but may include:
Developmental delays or regression in young children
Movement challenges such as dystonia, ataxia (unsteady walking), or parkinsonism (slowness, stiffness, tremors)
Speech and swallowing difficulties (dysarthria, dysphagia)
Cognitive decline or loss of previously learned skills
Eye problems, including optic atrophy that can lead to vision loss
Seizures, which may occur in some children
Over time, PLAN typically causes increasing disability. The rate of progression varies, even among individuals with the same diagnosis.
Diagnosis
PLAN is diagnosed through a combination of:
Clinical evaluation of symptoms and family history
MRI scans, which may show brain changes typical of NBIA
Genetic testing, which confirms mutations in the PLA2G6 gene
Early and accurate diagnosis is important to guide supportive care and connect families with specialists and research opportunities.
Inheritance
PLAN is inherited in an autosomal recessive manner. This means:
A child must receive one non-working copy of the PLA2G6 gene from each parent to develop the condition.
Parents who carry one altered copy are typically healthy but are “carriers.”
When two carriers have a child, there is a 25% chance the child will have PLAN, a 50% chance the child will be a carrier, and a 25% chance the child will not inherit the mutation.
Research & Support
Although there is currently no cure for PLAN, research is ongoing worldwide to better understand the condition and explore potential treatments, including:
Gene therapy approaches aimed at replacing or repairing the faulty gene
Neuroprotective strategies to slow progression
Symptom management therapies, such as medications for dystonia or parkinsonism, physical therapy, and assistive technologies
Families affected by PLAN are encouraged to connect with NBIA organizations and participate in registries and research studies, which are vital for advancing understanding and finding treatments.
