Clinical Guidance

Missense and splice site variants are more often associated with later onset and mild disease severity .

Source: GeneReviews — "Spastic Paraplegia 11"

Diagnostic Criteria

Suggestive Findings

Spastic paraplegia 11 (SPG11) should be suspected in individuals with the following clinical and imaging findings.

Frequent clinical findings

• Progressive spasticity and weakness of the lower limbs

• Mild intellectual disability with learning difficulties in childhood and/or progressive cognitive decline with onset in the first to third decade

• Axonal, motor, or sensorimotor peripheral neuropathy (80% of individuals) [, , , , , ]

• Pseudobulbar involvement with dysarthria and/or dysphagia

• Increased reflexes in the upper limbs

Less frequent clinical findings

• Cerebellar signs (ataxia or ocular signs including nystagmus and/or saccadic pursuit)

• Retinal degeneration (Kjellin syndrome)*

• Pes cavus

• Scoliosis

• Extrapyramidal signs such as parkinsonism

Source: GeneReviews — "Spastic Paraplegia 11"

Differential Diagnosis

See Hereditary Spastic Paraplegia Overview. The relative frequency of spastic paraplegia 11 (SPG11) varies according to phenotype and geographic origin. In Portugal, it accounts for 13% of all forms of spastic paraplegia regardless of the inheritance mode . SPG11 accounts for 5%-20% of autosomal recessive spastic paraplegias and up to 30%-50% of autosomal recessive complex spastic paraplegia . This frequency increases up to 59%-70% when mental impairment and thinning of the corpus callosum are associated. SPG11 pathogenic variants can be found in a small proportion of individuals with a pure spastic paraplegia (10%) but disease duration usually fewer than five years . There are other forms of spastic paraplegia associated with thinning of the corpus callosum and mental impairment and it is often difficult to distinguish them from SPG11 on clinical grounds. Table 2. Other Hereditary Spastic Paraplegias Associated with Thin Corpus Callosum (HSP-TCC) and Mental Impairment of Interest in the Differential Diagnosis of Spastic Paraplegia 11 (SPG11)

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with spastic paraplegia 11 (SPG11), the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Neuropsychological testing to assess the cognitive impairment and decline

• Neuro-urologic examination for those with sphincter disturbance

• Electrophysiologic investigations (e.g., ENMG, VEP, SEP)

• Ocular investigations (e.g., funduscopic examination, OCT)

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

No specific drug treatment or cure exists for SPG11. Care by a multidisciplinary team that may include a general practitioner, neurologist, clinical geneticist, physiotherapist, physical therapist, social worker, and psychologist should be considered. Symptomatic treatment to reduce pyramidal hyperactivity in the lower limbs includes the following:

• Physiotherapy for stretching of the spastic muscles to prevent contractures. Adapted dance or movements are also helpful to maintain strength (see www.clickanddance.com).

• Antispastic drugs such as baclofen and tizanidine

• Botulin toxin and intrathecal baclofen, which can be considered when oral drugs are ineffective and spasticity is severe and disabling

Source: GeneReviews — "Spastic Paraplegia 11"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Spastic Paraplegia 11"

Surveillance Guidelines

Specialized outpatient clinic evaluations are suggested every six months to adjust medication and physical rehabilitation that will depend on disease severity. Annual brain MRI can be used to follow the atrophy of the corpus callosum, cerebellum, and brain stem, and to monitor increases in the size and intensity of white matter hyperintensities. Annual electrophysiologic investigations (e.g., ENMG, VEP, SEP) are recommended to follow the extent of the disease. Visual acuity should be assessed annually.

Source: GeneReviews — "Spastic Paraplegia 11"