Clinical Guidance

No genotype-phenotype correlations for ZFYVE26 have been identified.

Source: GeneReviews — "Spastic Paraplegia 15"

Diagnostic Criteria

No consensus clinical diagnostic criteria for spastic paraplegia 15 (SPG15) have been published.

Suggestive Findings

Spastic paraplegia 15 (SPG15) should be suspected in individuals with the following clinical and brain imaging findings and family history.

Clinical findings

• Spasticity and weakness with progression from a spastic diplegia to a spastic tetraplegia with associated pyramidal signs (Babinski sign, hyperreflexia, ankle clonus)

• Learning disability or intellectual disability, progressive cognitive impairment

• Dysarthria and cerebellar signs

• Peripheral neuropathy (axonal sensorimotor neuropathy)

• Distal amyotrophy/ loss of muscle bulk

• Less common:

• Extrapyramidal movement disorders including focal dystonia and parkinsonism

• Retinopathy

• Sensorineural hearing impairment

• Epilepsy

• Cataracts

Source: GeneReviews — "Spastic Paraplegia 15"

Differential Diagnosis

SPG15 is one of the more common forms of complex hereditary spastic paraplegia with onset typically during childhood or adolescence. The initial clinical presentation of SPG15 is often nonspecific. A clinical differential diagnosis, after exclusion of acquired causes of spasticity, is best built on the combination of spasticity and neuroimaging findings. The most common neuroimaging findings: • Thinning of the corpus callosum • Signal abnormalities of the periventricular white matter • Cerebral and/or cerebellar atrophy While these findings are not specific, they can help guide a differential diagnosis. A thin corpus callosum is found in a number of hereditary spastic paraplegias. In SPG15, thinning of the corpus callosum tends to be identified in the anterior parts, in contrast to the AP-4-associated hereditary spastic paraplegias (SPG47, SPG50, SPG51, and SPG52) and others in which thinning of the corpus collosum is typically identified in the posterior parts . Similar to SPG11, the periventricular white matter signal changes in SPG15 can have a characteristic appearance involving the forceps minor. This is known as the "ears of the lynx sign," consisting of hypointense signal on T1-weighted images and hyperintense signal on FLAIR images which, on axial views, resembles the shape of the ears of a lynx with its characteristic apical hair tuft . (Note: It is also very difficult to distinguish SPG15 from SPG11 on clinical grounds alone and both disorders share a common molecular mechanism .) In addition to SPG11, overlapping clinical features exist with other forms of complex hereditary spastic paraplegia associated with thinning of the corpus callosum . Table 3. Autosomal Recessive Hereditary Spastic Paraplegias Associated with Thin Corpus Callosum (HSP-TCC) in the Differential Diagnosis of Spastic Paraplegia 15

Management Guidelines

No clinical practice guidelines for spastic paraplegia 15 (SPG15) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with spastic paraplegia 15 (SPG15), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Spastic Paraplegia 15

Source: GeneReviews — "Spastic Paraplegia 15"

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 15"

Surveillance Guidelines

Affected individuals should be evaluated periodically (i.e., every 6-12 months) by an interdisciplinary team that may include a neurologist, clinical geneticist, developmental specialist, orthopedic surgeon/physiatrist, physical therapist, occupational therapist, and speech and language pathologist, and feeding team to assess disease progression, maximize ambulation and communication skills, and reduce other manifestations.

Table 6.

Recommended Surveillance for Individuals with Spastic Paraplegia 15

System/Concern | Evaluation | Frequency

Neurologic

| Monitor treat spasticity extrapyramidal movement disorders. | At least annually, more frequently if needed

Musculoskeletal

|

• PT/OT eval

• Monitor for musculoskeletal complications of spasticity.

• Hip/spine x-rays as needed

Eyes | Ophthalmologic eval for visual acuity need for support services for the visually impaired | As needed

Gastrointestinal/

Nutrition

|

• Eval of aspiration risk nutritional status

• Consider eval for gastric tube placement in those w/dysphagia or aspiration risk.

Pulmonary

| Monitor for aspiration pulmonary complications.

Genitourinary

|

• Monitor bladder function.

• Monitor for urinary tract infections.

• Urodynamic testing

Mental health

| Monitor for depression or mood disorder.

Family support resources

| Monitor family/caregiver needs resources (social work involvement, home nursing referral)

OT = occupational therapy; PT = physical therapy

Source: GeneReviews — "Spastic Paraplegia 15"