Clinical Guidance

To date, no genotype-phenotype correlations have been identified.

Source: GeneReviews — "NARS1-Related Neurologic Disorders"

Diagnostic Criteria

No consensus clinical diagnostic criteria for NARS1-related neurologic disorders have been published.

Suggestive Findings

A NARS1-related neurologic disorder should be considered in a proband with the following clinical and neuroimaging findings and family history.

NARS1-Related Neurodevelopmental Disorder (NARS1-NDD)

Clinical findings

• Global developmental delay

Source: GeneReviews — "NARS1-Related Neurologic Disorders"

Differential Diagnosis

NARS1-related neurodevelopmental disorder (NDD). Because the phenotypic features associated with NARS1-NDD are nonspecific, other disorders with developmental delays/ intellectual disability, microcephaly, and epilepsy without other distinctive findings should be considered in the differential diagnosis. See OMIM Phenotypic Series for genes associated with:

• Autosomal dominant intellectual developmental disorders;

• Autosomal recessive intellectual developmental disorders;

• Syndromic X-linked intellectual developmental disorders.

NARS1-related hereditary neuropathy. See Charcot-Marie-Tooth Hereditary Neuropathy Overview.

Source: GeneReviews — "NARS1-Related Neurologic Disorders"

Management Guidelines

No clinical practice guidelines for NARS1-related neurologic disorders have been published. In the absence of published guidelines for NARS1-related neurodevelopmental disorder (NARS1-NDD), the following recommendations are based on the authors' personal experience managing individuals with this disorder. For information on the management of NARS1-related hereditary neuropathy, see Charcot-Marie-Tooth Hereditary Neuropathy Overview, Management.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with NARS1-NDD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

NARS1-Related Neurodevelopmental Disorder: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Neurologic

| Neurologic eval | • Assess for ataxia (e.g., SARA) peripheral neuropathy (nerve conduction studies).

• To include brain MRI if not performed at the time of diagnostic eval

• Consider EEG if seizures are a concern.

Development

| Developmental assessment | • To incl motor, adaptive, cognitive, speech/language eval

• Eval for early intervention/ special education

Speech delay

| By speech-language pathologist | Assess at age 9-12 mos

Musculoskeletal

| By orthopedist | To incl assessment for scoliosis/kyphoscoliosis

Physical medicine rehab/ PT OT eval | To incl assessment of:

Source: GeneReviews — "NARS1-Related Neurologic Disorders"

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 — "NARS1-Related Neurologic Disorders"

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 5. NARS1-Related Neurodevelopmental Disorder: Recommended Surveillance

Source: GeneReviews — "NARS1-Related Neurologic Disorders"