OMIM ID:
Spastic Paraplegia 74
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Onset of visual impairment occurs at ages of 10-14 years with optic pallor evident on fundoscopy. MRI imaging reveals physical atrophy of the optic nerve. Visual acuity ranges from 0.5 to finger counting. Visual field defects include central scotomas and peripheral concentric constriction.
Systemic Features
Symptoms consisting of a spastic gait and distal sensory impairment usually appear in the first decade and are slowly progressive. Increased deep tendon reflexes and extensor plantar responses may be present at that time but later distal leg muscle atrophy and pes cavus appear. The ankle reflexes later disappear. Cognitive function is normal and adults are able to lead an independent life.
Nerve conduction studies in 4 individuals showed reduced muscle action potentials and velocity while sensory conduction was normal. Cerebellar atrophy along with an attenuated corpus callosum and cervical spinal cord atrophy was noted on MRI imaging in one of 3 studied patients.
Genetics
Inheritance
A homozygous splice site mutation in IBA57 (1q42) has been found to segregate with this condition in a large consanquineous Arab family.
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.