OMIM ID:
Spastic Paraplegia 46
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Congenital cataracts (not further described) have been reported in several individuals with this type of complicated spastic paraplegia. Optic atrophy and nystagmus have not been reported.
Systemic Features
Stiffness and weakness of the lower limbs begins between 2 and 20 years of age. This is slowly progressive although most individuals are still mobile with mild to moderate handicaps into the 4th decade. The gait is spastic with weakness, hyperreflexia, and extensor plantar responses in the lower limbs. The upper limbs are variably involved and movements are dysmetric. Dysarthria and bladder dysfunction are often present. Cerebellar ataxia is common and some patients first present with this as a prominent sign in the first and second decades. Early cognitive development is normal but mild cognitive decline appears eventually. Pes cavus and scoliosis may occur.
Brain imaging can show thinning of the corpus callosum, with mild cerebellar and cerebral atrophy.
Genetics
Inheritance
Linkage analysis identified a locus at 9p13.3 and sequencing confirmed homozygous or compound heterozygous mutations in GBA2. The presence of parental consanguinity in some families supports autosomal recessive inheritance.
This database contains two other types of autosomal spastic paraplegia with ocular signs: spastic paraplegia 15 (270700) with a “flecked retina”, and spastic paraplegia 7 (607259) with optic atrophy and nystagmus. Cataracts have not been reported in these two conditions.
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.