Clinical Guidance

No clear genotype-phenotype correlations have been identified. While affected family members often share the same phenotype, intrafamilial variability has also been reported. For example, individuals from one Chinese family with the same DCTN1 pathogenic variant presented with dHMN7B, Perry syndrome, or overlapping features of dHMN7B-Perry syndrome .

Source: GeneReviews — "DCTN1-Related Neurodegeneration"

Penetrance

Although precise estimates have not been calculated given the limited number of families reported, penetrance is age related and high, with all asymptomatic heterozygotes being younger than or within the range of age of onset.

Source: GeneReviews — "DCTN1-Related Neurodegeneration"

Diagnostic Criteria

Suggestive Findings

DCTN1-related neurodegeneration should be suspected in individuals with any combination of the following clinical features, family history of the following features, or neuroimaging findings.

Clinical findings

• Parkinsonism

• Mood/personality/cognitive changes (depression, apathy, withdrawal, disinhibition, dementia)

• Weight loss

• Breathing disturbances (in particular central hypoventilation)

• Muscle atrophy

• Autonomic dysfunction

• Vocal fold paralysis

• Facial weakness

Family history is consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations). Absence of a known family history does not preclude the diagnosis. Neuroimaging and other studies [, , , , , , , , , , , , ]

Source: GeneReviews — "DCTN1-Related Neurodegeneration"

Differential Diagnosis

Table 2. Disorders of Interest in the Differential Diagnosis of DCTN1-Related Neurodegeneration

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with DCTN1-related neurodegeneration, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with DCTN1-Related Neurodegeneration

Source: GeneReviews — "DCTN1-Related Neurodegeneration"

Clinical Guidance

Use of central respiratory depressants (e.g., benzodiazepines, alcohol, narcotics) should be minimized.

Source: GeneReviews — "DCTN1-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 — "DCTN1-Related Neurodegeneration"

Surveillance Guidelines

Evaluate weight and calorie intake, respiratory function (particularly at night or during sleep), motor function, and mood/personality changes annually or more frequently as needed.

Source: GeneReviews — "DCTN1-Related Neurodegeneration"