OMIM ID:
Spastic Paraplegia 78
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Reduced upgaze with nystagmus and strabismus have been reported.
Systemic Features
This progressive neurodegenerative disorder usually has its onset in young adults but the signs and symptoms are highly variable. Ambulation and gait difficulties combined with spasticity and lower limb weakness are common signs. Ataxia and dysarthria are also important signs. Some individuals have dementia while others have only mild cognitive impairment. Some individuals have mild signs of Parkinsonism.
Brain imaging may show cerebellar and cortical atrophy with a thin corpus callosum.
Genetics
Inheritance
This condition results from homozygous or compound heterozygous mutations in the ATP13A2 gene (1p36.13).
The same gene is also mutated in the Kufor-Rakeb syndrome (606693), an early-onset form of Parkinsonism.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.