Clinical Guidance

Although clinical variability is observed with HMERF-related TTN variants, no relationship between the pathogenic variant and phenotype is evident.

Source: GeneReviews — "Hereditary Myopathy with Early Respiratory Failure"

Penetrance

Penetrance appears to depend on the pathogenic variant. For the common variant, penetrance appears to be complete, although individuals with very late-onset disease have been described (as late as age 71 years); therefore, it is possible that some affected individuals may die from other causes before the disease becomes manifest. The variant appears to have reduced penetrance in at least one family, where only one of two heterozygous family members developed the disease. Because the other pathogenic variants have only been described in a few individuals to date [, , , , , ], data are insufficient to draw conclusions regarding their penetrance; however, current observations suggest complete penetrance.

Source: GeneReviews — "Hereditary Myopathy with Early Respiratory Failure"

Diagnostic Criteria

Hereditary myopathy with early respiratory failure (HMERF) is a slowly progressive myopathy with typical onset in adulthood. The diagnosis of this rare disorder is not supported by any formal diagnostic criteria at this time.

Suggestive Findings

Diagnosis of hereditary myopathy with early respiratory failure (HMERF) should be suspected in individuals with the following:

Source: GeneReviews — "Hereditary Myopathy with Early Respiratory Failure"

Differential Diagnosis

Table 2. Disorders to Consider in the Differential Diagnosis of Hereditary Myopathy with Early Respiratory Failure

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with hereditary myopathy with early respiratory failure (HMERF), 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 HMERF

Source: GeneReviews — "Hereditary Myopathy with Early Respiratory Failure"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Hereditary Myopathy with Early Respiratory Failure"

Surveillance Guidelines

No specific guidelines are in place for surveillance of this disorder; general recommendations are provided in .

Table 5.

Recommended Surveillance for Individuals with HMERF

System/Concern | Evaluation | Frequency

Neuromuscular

| Reassessment of muscle strength clinical status w/neurologist who can coordinate any additional required services | Annually

Respiratory

| Pulmonary function testing | Every 6-12 mos or guided by individual findings

Source: GeneReviews — "Hereditary Myopathy with Early Respiratory Failure"