MECR-Related Neurologic Disorder

Excerpt

Clinical characteristics: MECR-related neurologic disorder is characterized by a progressive childhood-onset movement disorder and optic atrophy; intellect is often – but not always – preserved. The movement disorder typically presents between ages one and 6.5 years and is mainly dystonia that can be accompanied by chorea and/or ataxia. Over time some affected individuals require assistive devices for mobility. Speech fluency and intelligibility are progressively impaired due to dysarthria. Optic atrophy typically develops between ages four and 12 years and manifests as reduced visual acuity, which can include functional blindness (also known as legal blindness) in adulthood. Because only 13 affected individuals are known to the authors, and because nearly half of them were diagnosed retrospectively as adults, the natural history of disease progression and other aspects of the phenotype have not yet been completely defined.

Diagnosis/testing: The diagnosis of MECR-related neurologic disorder is established in a proband with a childhood-onset movement disorder and biallelic (compound heterozygous or homozygous) pathogenic variants in MECR identified by molecular genetic testing.

Management: Treatment of manifestations: Visual aids for decreased visual acuity due to optic atrophy; occupational therapy and physical therapy to maintain range of movement and special aids (e.g., braces, walkers, wheelchairs) to maintain/improve mobility; speech therapy for dysarthria and augmentative communication if needed. Medications that may relieve dystonia include anticholinergic agents, baclofen, and benzodiazepines.

Surveillance: The following yearly examinations are warranted: ophthalmologic (need for additional visual aids), neurologic (need for medications to relieve dystonia), speech therapy (need for augmentative communication), cognitive evaluation, and feeding evaluation (assess risk of aspiration).

Agents/circumstances to avoid: Stress and febrile illness as much as possible as these are presumed to exacerbate disease progression. Discuss anesthetic risks with a patient's medical team prior to surgical procedures.

Genetic counseling: MECR-related neurologic disorder is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the MECR pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic diagnosis are possible.