Clinical Guidance

POLG-related disorders comprise a continuum of broad and overlapping phenotypes that range from fatal neonatal-onset disease to mild late-onset disease with myopathy and progressive external ophthalmoplegia (PEO). Although some affected individuals present with one of the clinical entities caused by POLG pathogenic variants, many have some, but not all, of the features of one or more of the recognized phenotypes. Although clinical phenotypes in affected individuals from the same family are often similar, ages of onset, specific features, and rate of progression may differ. POLG-related disorders can therefore be considered an overlapping spectrum of disease presenting from early childhood to late adulthood. The age of onset broadly correlates with the clinical phenotype . summarizes the clinical findings in POLG-related disorders. Table 2. Clinical Findings in POLG-Related Disorders

Diagnostic Criteria

Suggestive Findings

POLG-related disorders comprise a continuum of overlapping phenotypes. A POLG-related disorder should be suspected in individuals with combinations of the following clinical features and laboratory and neuroimaging findings. Clinical features. Clinical features form a continuum but vary in their age of onset. Apart from progressive external ophthalmoplegia (PEO)/ ptosis, other features could present at any time from infancy to adulthood. The most common clinical features by age of onset are:

• Prior to age 12 years (early-onset disease):

Management Guidelines

No clinical practice guidelines for POLG-related disorders have been published, although consensus statement guidelines for primary mitochondrial diseases are available .

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with POLG-related disorder, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Evaluation should always include measures of functional neurologic status.

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, evaluations by a multidisciplinary team including neurologist, biochemical geneticist, hepatologist or gastroenterologist, physiatrist, psychiatrist, neuropsychologist and/or psychologist, ophthalmologist, and pulmonologist are recommended. No standard-of-care guidelines regarding the recommended frequency of evaluations exist; surveillance should be guided by clinical features, and the schedule should be modified if the clinical course is stable. For those with the most severe phenotypes, the recommendations in can be considered.