Clinical Guidance

No genotype-phenotype correlations have been observed with recurrent pathogenic variants.

Source: GeneReviews — "Pelizaeus-Merzbacher-Like Disease 1"

Diagnostic Criteria

Suggestive Findings

Pelizaeus-Merzbacher-like disease 1 (PMLD1) should be suspected in individuals with the following classic clinical and neuroimaging findings:

Clinical findings

• Nystagmus that typically presents during the neonatal period or early infancy

• Mainly motor developmental delay and central hypotonia during infancy

• Signs of upper motor neuron dysfunction (including spasticity, brisk deep tendon reflexes, and Babinski sign) usually affecting the lower limbs more than the upper limbs

• Gait ataxia and other cerebellar signs

• Mild choreiform movements and dystonia of the extremities that can become severe and disabling

• Dysarthria and swallowing dysfunction

Neuroimaging findings. Findings on brain MRI include the following :

Source: GeneReviews — "Pelizaeus-Merzbacher-Like Disease 1"

Differential Diagnosis

Pelizaeus-Merzbacher disease

(PMD) is an X-linked disorder caused by a hemizygous pathogenic variant in PLP1. The clinical presentation and radiologic appearance are similar to PMLD1. Most individuals present with neonatal nystagmus, hypotonia, global developmental delay, spasticity, gait ataxia, and choreoathetosis. Diffuse hypomyelination on brain MRI is observed in most individuals. Note that MRI evidence of brain stem involvement is more characteristic of PMLD1 than PMD. Both PMD and PMLD1 can present as an isolated spastic paraparesis; see . Hypomyelination with atrophy of the basal ganglia and cerebellum (see TUBB4A-Related Leukodystrophy) is caused by a heterozygous pathogenic variant in TUBB4A; affected individuals are typically simplex cases (i.e., a single occurrence in a family).

Source: GeneReviews — "Pelizaeus-Merzbacher-Like Disease 1"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Pelizaeus-Merzbacher-like disease 1 (PMLD1), the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis of Pelizaeus-Merzbacher-Like Disease 1

Source: GeneReviews — "Pelizaeus-Merzbacher-Like Disease 1"

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 — "Pelizaeus-Merzbacher-Like Disease 1"

Surveillance Guidelines

Table 6. Recommended Surveillance for Individuals with Pelizaeus-Merzbacher-Like Disease 1

Source: GeneReviews — "Pelizaeus-Merzbacher-Like Disease 1"