Clinical Guidance

DYNC1H1-related disorders are primarily characterized by an axonal neuropathy with a wide phenotypic spectrum, ranging from a neuromuscular-only phenotype (DYNC1H1-related neuromuscular disorder) to phenotypes involving both the central nervous system and peripheral nervous system referred to collectively as DYNC1H1-related neurodevelopmental disorder . DYNC1H1-related neuromuscular disorder (DYNC1H1-NMD). Manifestations are limited to the peripheral nervous system (PNS) and characterized predominantly by motor neuropathy, initially most pronounced in the lower limbs; muscle weakness and atrophy variably associated with foot deformities, contractures, and other skeletal involvement; and/or delayed motor milestones. DYNC1H1-related neurodevelopmental disorder (DYNC1H1-NDD). Manifestations include motor axonal neuropathy and global developmental delay/ intellectual disability, epilepsy, neurobehavioral/psychiatric manifestations, and movement disorders with or without malformations of cortical development (MCD) and or microcephaly. In an individual with more significant central nervous system (CNS) involvement, the motor axonal neuropathy may not be evident clinically and thus only detected on further evaluation such as electrophysiologic testing. To date, more than 200 individuals with DYNC1H1-related disorders have been identified . The following comparison of the two phenotypic designations for DYNC1H1-related disorders is based on these reports (see and ). Table 2. DYNC1H1-Related Disorders: Comparison of Presentations at Initial Evaluation

Diagnostic Criteria

Suggestive Findings

A DYNC1H1-related disorder should be considered in a proband with the following age-related clinical and electrophysiologic findings of axonal neuropathy with or without developmental delay/ intellectual disability and related central nervous findings, as well as family history.

DYNC1H1-Related Neuromuscular Disorder (DYNC1H1-NMD)

Axonal neuropathy. At all ages across the phenotypic spectrum of DYNC1H1-related disorders:

Management Guidelines

No clinical practice guidelines for DYNC1H1-related disorders have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with a DYNC1H1-related disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 7. DYNC1H1-Related Disorders: Recommended Surveillance