Clinical Guidance

No clinically relevant genotype-phenotype correlations have been reported for GAN-related neurodegeneration. Family members with the same pathogenic variant and different clinical phenotypes have been reported .

Source: GeneReviews — "GAN-Related Neurodegeneration"

Diagnostic Criteria

No consensus clinical diagnostic criteria for GAN-related neurodegeneration have been published.

Suggestive Findings

GAN-related neurodegeneration should be suspected in individuals with the following clinical, electrophysiologic, and brain imaging findings, and family history.

Clinical findings

Source: GeneReviews — "GAN-Related Neurodegeneration"

Differential Diagnosis

Hereditary Disorders in the Differential Diagnosis of Classic Giant Axonal Neuropathy At onset, classic giant axonal neuropathy (GAN) presents with features (e.g., neuropathic deficits, giant axons, and neurofilament aggregation) similar to those associated with several severe, early-onset hereditary motor and sensory neuropathies . These neuropathies and other disorders of interest in the differential diagnosis of classic GAN are summarized in . Table 3. Genes of Interest in the Differential Diagnosis of Classic Giant Axonal Neuropathy

Management Guidelines

No clinical practice guidelines for GAN-related neurodegeneration have been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with GAN-related neurodegeneration, 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 GAN-Related Neurodegeneration

System/Concern

|

Evaluation

|

Comment

Extent of

neurologic

involvement | Complete neurologic exam |

Assess LMN dysfunction: weakness, amyotrophy, sensory loss. | • Assessment to incl cranial nerve dysfunction (See Ophthalmologic involvement in this table.)

• Consider motor sensory NCV to document a sensorimotor axonal pattern of neuropathy.

Assess UMN dysfunction: spasticity, Babinski signs, hyperreflexia. |

Assess 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).1,2

EEG brain MRI (if not previously performed) if seizures are a concern |

Motor disability

ADL | Orthopedics / physical medicine rehab / PT / OT eval | To incl assessment of:

• Gross motor fine motor skills

• Mobility, ADL need for adaptive devices

• Need for PT (to improve gross motor skills) /or OT (to improve fine motor skills)

ID / Cognitive

Source: GeneReviews — "GAN-Related Neurodegeneration"

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 — "GAN-Related Neurodegeneration"

Surveillance Guidelines

Surveillance is individualized and involves monitoring response to ongoing interventions and identifying new manifestations. Surveillance may involve some or all of the recommendations in .

Table 6.

Recommended Surveillance at Each Visit for Individuals with GAN-Related Neurodegeneration

System/Concern | Evaluation

Development /

Cognitive decline

| Monitor developmental progress educational needs.1

Neurologic

| • Monitor those w/seizures as clinically indicated.

• Assess progression of peripheral neuropathy, ataxia, spasticity, cranial nerve dysfunction.

Motor disability ADL

| Physical medicine, OT/PT assessment of mobility, self-help skills

Wheelchair-bound

or bedridden persons | Examine for bedsores decubitus ulcers.

Dysarthria /

Language delay

| Speech-language pathology assessment

Feeding

| • Measurement of growth parameters

• Eval of nutritional status safety of oral intake

Optic atrophy

| • Eye exam (visual acuity, color vision testing, slit lamp exam for cataracts, fundoscopy, visual fields)

• Evaluate effectiveness of low-vision aids.

OT = occupational therapist; PT = physical therapist

1. Frequent reassessment is needed because of the progressive nature of the disorder. Special education often becomes necessary between ages five and 12 years.

Source: GeneReviews — "GAN-Related Neurodegeneration"