Spastic paraplegia type 7 (ORPHA:99013)
A form of hereditary spastic ataxia characterized by an onset usually in adulthood (but ranging from 10-72 years) of progressive bilateral lower limb weakness and spasticity and sometimes predominant cerebellar ataxia. In addition to frequent sphincter dysfunction and decreased vibratory sense at the ankles, manifestations may include optical neuropathy, nystagmus, blepharoptosis, ophthalmoplegia, decreased hearing, scoliosis, pes cavus, motor and sensory neuropathy, muscle atrophy, parkinsonism, and dystonia.
Epidemiology
The worldwide prevalence of autosomal dominant and autosomal recessive spastic paraplegia (SPG) combined is about 1.8 /100.000, the prevalence of SPG type 7 is unknown.
Clinical description
The disease onset is typically between the third and fifth decade, even though earlier or later onset are reported (10-72 years). The clinical presentation can be a pure spastic paraplegia (pyramidal syndrome, sphincter dysfunction, lower limbs weakness, diminished vibration sense, pes cavus) mostly associated with, cerebellar ataxia. Optic atrophy, ptosis and oculomotor abnormalities (nystagmus, progressive external ophthalmoplegia, saccadic pursuit) are frequently associated. Additional neurological signs are spastic dysarthria, dysphagia, parkinsonism, dystonia, scoliosis, hearing loss, and cognitive impairment. Brain magnetic resonance imaging nearly always shows a cerebellar atrophy and electromyography can detect a motor and sensory neuropathy.
Etiology
The disease is due to biallelic pathogenic variants in the SPG7 gene (chromosome 16q24.3) coding for paraplegin protein.
Diagnostic methods
Diagnosis is suspected on clinical presentation and confirmed by genetic testing (panel sequencing of hereditary spastic paraplegia genes, exome or genome analysis).
Differential diagnosis
The differential diagnosis includes autosomal dominant and recessive spastic paraplegias, spinocerebellar ataxias (e.g. Spinocerebellar ataxia type 28), adrenomyeloneuropathy and other leukodystrophies, amyotrophic lateral sclerosis, and primary progressive multiple sclerosis.
Antenatal diagnosis
Prenatal diagnosis is possible if the pathogenic variants are known and present in at risk couples (where both parents are heterozygous carriers).
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy. Few cases of dominant transmission are reported, individuals carrying one pathogenic variant could present signs (e. g. mild cerebellar atrophy, peripheral neuropathy) or symptoms (e. g. cerebellar ataxia, brisk deep tendon reflexes).
Management and treatment
The treatment is symptomatic, including myorelaxants (oral or intrathecal baclofen, dantrolene, intramuscular botulinum toxin, etc.), bladder control medications, anti-parkinsonian drugs (L-Dopa, dopamine-agonists). Physical, occupational, and speech therapy should be proposed in association with medication.
Prognosis
The disease course is variable but often the walking autonomy is decreased requiring the use of a wheelchair. The disease strongly affects the quality of life.

                            Last update: 
                            November 2021


                            - Expert reviewer(s): 
                            Dr Giulia COARELLI | ERN-RND* - Pr Alexandra DURR | ERN-RND*


                                * European Reference Network