LAMA2-related Muscular Dystrophy Brain Study

Cure Cmd

Status: Withdrawn

Conditions: LAMA2-MD (Merosin Deficient Congenital Muscular Dystrophy, MDC1A)

Study type: Observational

Funder types: Other

Identifiers

NCT01952028

CMDIR-003

Details and patient eligibility

About

Laminin alpha-2 (LAMA2)-related muscular dystrophy (LAMA2-MD, Merosin Deficient CMD) is a form of congenital muscular dystrophy (CMD). A person with LAMA2-MD will have changes on brain imaging (MRI), a decrease or absence of the protein merosin (laminin 211) on muscle or skin biopsy and changes in the LAMA2 gene that are inherited from both parents. Several studies have described the changes on brain MRI. Brain changes on MRI do not correlate with the partial reduction or absence of merosin on muscle or skin biopsy. 8-30% of people with LAMA2-MD develop seizures. The types of seizures, electroencephalogram changes and common treatment regimens have not been characterized. This study will review the magnetic resonance imaging (MRI) changes, determine whether certain brain MRI changes are linked to seizures and define the common seizure treatment regimens.

Full description

LAMA2-MD is a congenital muscular dystrophy (CMD) subtype caused by mutations in the laminin alpha 2 gene. LAMA2-MD may present clinically as an early onset, severe phenotype or a late onset limb girdle phenotype. The early onset form is most commonly associated with a complete absence of merosin on muscle biopsy with profound neonatal hypotonia, possible respiratory distress and feeding difficulties while the late onset form presents with proximal muscle weakness, contractures and is able to achieve walking. In both early and late onset forms, brain white matter abnormalities have been described on brain MRI and approximately 8-30% develop a seizure disorder. On magnetic resonance (MR) spectroscopy, white matter changes are shown to be due to increased water content rather than areas of demyelination. Both, non-ambulant and ambulant patients may develop respiratory insufficiency requiring non-invasive ventilation and scoliosis.

Although several studies have evaluated the correlation between brain MRI white matter changes and cognition, no studies to date have provided a systematic evaluation of brain imaging, electrophysiologic testing and seizures in patients identified by molecular or immunohistochemical testing to have LAMA2-MD.

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Genetic confirmation of 2 variants in LAMA2 gene OR muscle biopsy with complete absence of merosin
• Complete authorization to obtain medical records for Congenital Muscle Disease International Registry
• Complete authorization to obtain medical records for National Institutes of Health (NIH)
• Reside in United States or Canada
• Complete registration and intake survey in the Congenital Muscle Disease International Registry

Exclusion criteria

• Individuals with LAMA2-MD who have not had a brain MRI