Clinical Characteristics
Ocular Features
Many but not all individuals have significant visual loss due to optic atrophy. Other ocular signs include supranuclear palsy, ptosis, and nystagmus. Older individuals with advanced disease may have progressive external ophthalmoplegia.
Systemic Features
There is a great deal of clinical heterogeneity between families and not all individuals have severe neurological disease. Progressive neurological signs (primarily abnormal gait) are often present in late childhood or early adolescence but may occur late in life. Clinical features include muscle atrophy and weakness with spasticity (more pronounced in the lower limbs), ataxia, pyramidal signs, dysphagia, and cerebellar dysarthria. Hyperreflexia and extensor plantar responses are often present. Cognitive deficits are manifest as deficits in attention and higher levels of reasoning. Some patients have a mild peripheral neuropathy with decreased vibratory sense. Many patients have significant dysfunction of the bladder sphincter. Adults may lose their mobility and are confined to a wheelchair.
Some patients develop scoliosis and pes cavus. The MRI often shows cerebellar and mild frontal cortical atrophy.
Genetics
Inheritance
This type of spastic paraplegia results from mutations in the paraplegin gene, SPG7 (16q24.3). It is usually transmitted in an autosomal recessive pattern although heterozygous patients with symptoms have been reported. Evidence suggests that the symptoms arise from a defect in mitochondrial respiration.
Patients with spastic paraplegia 15 (270700) have a similar neurological phenotype plus a flecked retina. Congenital cataracts are part of the phenotype of spastic paraplegia 46 (614409).
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.