Clinical Guidance

Individuals with biallelic loss-of-function pathogenic variants typically have more pyramidal signs and optic atrophy compared to individuals who have at least one missense variant (see Table 1 in ). Individuals with at least one variant had slightly later age of onset and presented with a cerebellar phenotype when compared to individuals with loss-of-function pathogenic variants who had a more spasticity-predominant phenotype (see Table 2 in ).

Source: GeneReviews — "SPG7-Related Neurologic Disorder"

Diagnostic Criteria

No consensus clinical diagnostic criteria for SPG7-related neurologic disorder have been published.

Suggestive Findings

The diagnosis of SPG7-related neurologic disorder should be considered in probands with the following clinical and imaging findings and family history .

Clinical findings

Source: GeneReviews — "SPG7-Related Neurologic Disorder"

Differential Diagnosis

Spastic paraplegia. The differential diagnosis of SPG7-related spastic paraplegia includes the following:

• Other types of uncomplicated (pure) hereditary spastic paraplegia (HSP) (see Uncomplicated [Pure] Hereditary Spastic Paraplegia Overview). No significant differences exist between SPG7-related spastic paraplegia and other types of uncomplicated autosomal dominant and autosomal recessive spastic paraplegia .

• Complicated HSP (characterized by the impairments present in uncomplicated HSP plus other system involvement or other neurologic findings such as ataxia, seizures, intellectual disability, dementia, muscle atrophy, optic nerve atrophy, extrapyramidal disturbance, and/or peripheral neuropathy)

• Other genetic disorders

• Acquired conditions

Source: GeneReviews — "SPG7-Related Neurologic Disorder"

Management Guidelines

No clinical practice guidelines for SPG7-related neurologic disorder have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with SPG7-related neurologic disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

SPG7-Related Neurologic Disorder: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Neurologic

| Assessment by neurologist for cerebellar motor dysfunction (gait postural ataxia, dysmetria, dysdiadochokinesis, tremor, dysarthria, nystagmus, saccades smooth pursuit) | Use standardized scale to establish baseline for ataxia (SARA, ICARS, or BARS).1

UMN /or LMN dysfunction (weakness, spasticity, Babinski signs, hyperreflexia, amyotrophy, fasciculations) | • Brain MRI /or spinal cord MRI may be indicated to rule out coincident pathologies.

• Consider referral to neuromuscular clinic.

Extrapyramidal features (e.g., dystonia, parkinsonism) | Use standardized scale to establish baseline for dystonia (BFMDRS, UDRS, or BADS).

Musculoskeletal/

ADL | OT PT, physiatry | To assess gross motor fine motor skills, gait, ambulation, as well as need for adaptive devices ongoing PT/OT

Orthopedics exam | To assess for pes cavus scoliosis

Ophthalmologic

| Comple...

Source: GeneReviews — "SPG7-Related Neurologic Disorder"

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 — "SPG7-Related Neurologic Disorder"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. In addition to the routine surveillance outlined in , it is important to monitor bedridden individuals with advanced disease to avoid potential complications from aspiration pneumonia, urinary tract infections, and pulmonary embolism. Table 5. SPG7-Related Neurologic Disorder: Recommended Surveillance

Source: GeneReviews — "SPG7-Related Neurologic Disorder"