PLP1

Spastic Paraplegia 2

Clinical Characteristics
Ocular Features: 

Nystagmus is common but variable in age of onset, and half of affected individuals have optic atrophy.

Systemic Features: 

This is a complex form of spastic paraplegia in which primarily lower limb spasticity is associated with dysarthria, sensory disturbances, cognitive deficits, muscle wasting and mild ataxia.  There is, however, considerable variability in age of onset and rate of symptom progression.  The first motor symptoms are often evident when children start walking, which is often delayed and clumsy.  However, evidence of spasticity may be present in children under 1 year of age.   Some patients have normal mental functions while others are considered mentally retarded.  The MRI reveals patchy leukodystrophy and degeneration of both corticospinal and spinocerebellar tracks was found in an autopsied individual.  Progression is relentless with many individuals requiring assistive devices such as crutches or walkers by early adult life.

Genetics

This is an X-linked disorder secondary to a mutation in the PLP1 gene at Xq22.2which codes for 2 major proteins found in myelin.  SPG2 is allelic to the more severe Pelizaeus-Merzbacher disease (312080).

Treatment
Treatment Options: 

Mobility devices and physical therapy can be helpful, especially in younger individuals.

References
Article Title: 

Pelizeaus-Merzbacher Disease

Clinical Characteristics
Ocular Features: 

Nystagmus is the major ocular feature in this disease and may appear as early as the first weeks of life in severe cases.  However, more mildly affected individuals may never have nystagmus and, further, it can disappear later.  The ocular movements are usually pendular but may have horizontal and rotatory components as well.  The presence of nystagmus is diagnostically important as it is an uncommon finding in other leukodystrophies.

Systemic Features: 

The classic disease is infantile in onset with hypotonia, titubation, weakness, stridor, respiratory problems, and even seizures often noted in the first weeks of life.   Ataxia, spasticity and cognitive delay are soon apparent.  Infants affected early and severely may never achieve normal motor or mental milestones whereas those less severely affected may at some point ambulate and acquire some language skills.  However, acquired skills may be lost by adolescence.  Survival to the sixth decade of life is common but those with the most severe form of disease may not live beyond the second decade. 

This is an X-linked recessive disorder in which only males have the complete syndrome.  However, multiple carrier females have been studied and many have subtle evidence of disease mainly in gait and motor control.

Genetics

Pelizeaus-Merzbacher disease is the result of mutations in an X-linked gene PLP1 (Xq22).  It is inherited in an X-linked recessive pattern.  Duplication of the PLP1 gene is more common than point mutations.  The signs and symptoms are not diagnostic of PMD as mutations in other genes can cause a similar phenotype. 

Spastic paraplegia-2 (SPG2; 312920)is an allelic disorder in which nystagmus and optic atrophy are also found in some patients.

Pedigree: 
X-linked recessive, carrier mother
X-linked recessive, father affected
Treatment
Treatment Options: 

There is no effective treatment for this disease.  Airway protection and seizure control should be applied in specific situations.  Patients often need a feeding tube for adequate nutrition.

References
Article Title: 
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