PLAN
PLAN, or PLA2G6-Associated Neurodegeneration, an inherited autosomal recessive disorder; named for the responsible gene: PLA2G6. This gene is thought to be important in helping cells maintain a healthy membrane (outer layer). It is involved in fat (lipid) metabolism.
It is not yet known how changes in this gene cause the symptoms of PLAN or high brain iron in some affected individuals.
This disorder is made up of three distinct forms with differing characteristics:
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INAD, or Infantile Neuroaxonal Dystrophy
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NAD, or atypical neuroaxonal dystrophy, which starts a few years later in life than INAD
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an adult form of PLA2G6-related dystonia-parkinsonism in which onset occurs in the second to third decade of life.
INAD
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INAD starts early in life and progresses rapidly.; usually developing between 6 months and 3 years of age.
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The first signs are often delays in developing skills, such as walking and talking.
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Children may be floppy or have low muscle tone early on, but this later turns into stiffness (spasticity) as they get older, especially in the arms and legs.
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Eye disease caused by the degeneration of the optic nerve (optic atrophy) is common later on and can cause poor vision and eventual blindness.
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Seizures and fast rhythms on an EEG may also occur.
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A loss of cognitive abilities occurs, and many affected children never learn to walk or lose the ability early on.
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Many affected children do not survive beyond their first decade, but some survive into their teens or later. Supportive care can contribute to a longer life span by reducing the risk of infection and other complications.
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Clinical Diagnosis of INAD
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An MRI of the brain and an eye exam are keys to diagnosing INAD.
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In addition to a loss of motor skills, affected individuals also experience cerebellar atrophy, strabismus (crossed eyes) and nystagmus (rapid involuntary eye movements).
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Abnormal axons (a part of nerve cells), called spheroid bodies, can be seen on biopsies but may not appear until later in the disease as they accumulate with age.
Managing INAD
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Drugs are given to treat spasticity and seizures.
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Fiber supplements and/or stool softeners are used to treat constipation.
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A transdermal scopolamine patch may help with mouth secretions.
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Feeding modifications such as softer foods or a feeding tube may be required to prevent aspiration pneumonia and achieve adequate nutrition
NAD
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NAD usually starts in early childhood, but can be as late as the end of the second decade.
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It has a slower progression and a different variety of movement problems than INAD.
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At first, children may have delays in speaking or exhibit features similar to autism.
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Eventually, difficulty with movement develops and these individuals usually have dystonia.
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Behavior changes are common, such as acting impulsively, not being able to pay attention for long periods of time, or becoming depressed, which may require treatment by a doctor.
Clinical Diagnosis of NAD
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Certain MRI views (T2-weighted images) that show a hypointense globus pallidus indicating iron accumulation and an eye exam are keys to establishing strong clinical features of NAD.
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Predominant features of NAD are onset before age 20, psychomotor regression (i.e. loss of previously acquired skills), language difficulties, autistic-like behavior, cerebellar atrophy, optic atrophy, progressive dystonia and dysarthria (difficulty pronouncing words).
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As with INAD, biopsies show evidence of abnormal axons called spheroid bodies.
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Other common features are psychiatric and behavior abnormalities, spasticity, joint contractures, seizures, and nystagmus (rapid involuntary eye movements).
Managing NAD
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Drug therapy is provided for spasticity and seizures.
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For dystonia, oral or intrathecal baclofen may be tried.
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Treatment by a psychiatrist is indicated for those with later-onset neuropsychiatric (mental disorder due to disease of the nervous system) symptoms.
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Fiber supplements and/or stool softeners are used to treat constipation.
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A transdermal scopolamine patch may help with mouth secretions.
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Feeding modifications such as softer foods or a feeding tube may be required to prevent aspiration pneumonia and achieve adequate nutrition.
PLA2G6-related dystonia-parkinsonism
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The onset of PLA2G6-related dystonia-parkinsonism varies from childhood to second and third decade of life.
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These individuals experience dystonia, eye movement abnormalities, slowness, poor balance, rigidity and marked cognitive decline.
Clinical Diagnosis of PLA2G6-related dystonia-parkinsonism
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Abnormal brain iron accumulation in the globus pallidus, substantia nigra and/or striatum varies among affected individuals and may not be evident on MRI studies until late in the disease.
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The main features are variable onset from childhood to young adulthood; parkinsonism (tremor, bradykinesia, rigidty, and impaired postural responses); dystonia; cognitive decline; neuropsychiatric (mental disorder due to disease of the nervous system) changes; and an initial dramatic response to dopaminergic (levodopa) treatment followed by the early development of dyskinesias (diminished voluntary movements and the presence of involuntary movements).
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Other common features are dysarthria (difficulty pronouncing words), autonomic involvement and mild cerebral atrophy.
Managing PLA2G6-related dystonia-parkinsonism
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Consider treating with dopaminergic agents.
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Consult a psychiatrist to treat neuropsychiatric symptoms.
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A physical therapy evaluation may help problems with posture and walking.
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Occupational therapy can help the person perform activities of daily living.
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Periodic assessment of vision and hearing may be needed.
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To prevent secondary complications: start physical therapy early and orthopedic management to help prevent contractures as the disease progresses.
Please see the link on this page for more detailed clinical information on PLAN at Gene Reviews, which was used as a source for some of the above information. Gene Reviews is primarily for the use of genetics professionals so the terminology and information may be difficult to understand for the general public.
Gene Review Authors: Allison Gregory, MS, CGC, Manju A Kurian, MA, MRCPCH, PhD, Eamonn R Maher, MD, FRCP, FMedSci, Penelope Hogarth, MD, and Susan J Hayflick, MD.
Please visit the NBIA Disorders Association website, which was used as a primary source for the above information.