Penetrance

Penetrance is difficult to estimate because few unaffected individuals in families with a CHCHD10-related disorder have been genotyped or longitudinally followed for the emergence of symptoms.

Source: GeneReviews — "CHCHD10-Related Disorders"

Diagnostic Criteria

Suggestive Findings

A CHCHD10-related disorder should be suspected in an individual with clinical findings of a mitochondrial myopathy, amyotrophic lateral sclerosis, frontotemporal dementia, late-onset spinal motor neuronopathy, or axonal Charcot-Marie-Tooth neuropathy, especially when the family history of these diverse phenotypes is consistent with autosomal dominant inheritance.

Clinical Findings

Mitochondrial myopathy. Signs of muscle weakness (proximal, axial, and/or facial, including ptosis), amyotrophy, or symptoms that suggest respiratory chain dysfunction, such as exercise intolerance Amyotrophic lateral sclerosis (ALS).

Source: GeneReviews — "CHCHD10-Related Disorders"

Differential Diagnosis

The differential diagnosis of CHCHD10-related disorders spans a wide spectrum of neurodegenerative diseases. All genes known to be associated with the predominant phenotype in an affected individual should be considered in the differential diagnosis. See the following GeneReviews for detailed review of genes associated with each phenotype:

• Amyotrophic Lateral Sclerosis Overview

• Charcot-Marie-Tooth Hereditary Neuropathy Overview

• Hereditary Ataxia Overview

• Mitochondrial myopathy (See Mitochondrial Disorders Overview.)

Source: GeneReviews — "CHCHD10-Related Disorders"

Management Guidelines

Consensus clinical management recommendations for CHCHD10-related disorders have not been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with a CHCHD10-related disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 2.

Recommended Evaluations Following Initial Diagnosis in Individuals with CHCHD10-Related Disorders

System/Concern | Evaluation | Comment

Neurologic

| Complete neurologic eval | To assess:

• UMN involvement: spasticity, Babinski signs, hyperreflexia

• LMN involvement: weakness, amyotrophy, fasciculations

• Muscle strength

• Coordination balance

EMG/NCS | To document regions of involvement indicate LMN /or myopathic involvement

Brain MRI |

Neuropsychological exam | To evaluate extent profile of cognitive disturbance

Speech swallowing eval | For those w/frequent choking or severe dysphagia, also assess:

• Nutritional status;

• Aspiration risk.

PT OT | To evaluate for need for adaptive devices to maximize function

Neuropsychiatric

| Screening for depression /or behavioral concerns | Assess need for psychosocial support behavioral therapy.

Pulmonary

| Pulmonary function testing | To detect stage respiratory involvement

Hearing

| Audiologic exam | Incl auditory brain stem response evoked otoacoustic emission testing

Nutrition

| Nutrition eval | Consider involving a gastroenterology/nutrition/feeding team, incl formal swallowing eval.

Genetic

Source: GeneReviews — "CHCHD10-Related Disorders"

Clinical Guidance

The following should be noted:

• Baclofen used to treat spasticity can sometimes worsen muscle weakness.

• Some drugs used to treat the behavioral manifestations of FTD may worsen dysarthria, dysphagia, and/or respiratory weakness.

Source: GeneReviews — "CHCHD10-Related Disorders"

Surveillance Guidelines

Table 4. Recommended Surveillance for Individuals with CHCHD10-Related Disorders

Source: GeneReviews — "CHCHD10-Related Disorders"