LAMA2-MD (Merosin Deficient Congenital Muscular Dystrophy, MDC1A)
Conditions
Keywords
MDC1A, Congenital Muscular Dystrophy, Merosin Deficient, LAMA2, brain white matter abnormalities, Seizure
Brief summary
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.
Detailed 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.
Interventions
None listed
Sponsors
Congenital Muscle Disease International Registr
Cure CMD
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identify and grade the structural brain abnormalities observed on MRI | up to 5 months | Both single and longitudinal brain MRIs will be retrieved with patient consent from hospitals within the United States. Two trained neuroradiologists will evaluate de-identified brain MRIs using a pre-determined scoring system to identify and classify structural abnormalities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seizure History | up to 8 months | To obtain a seizure history on all individuals with LAMA2-MD who have had a seizure, including: type of seizures, age of seizure onset, seizure frequency, need for mechanical ventilation, seizure medications, and need for emergency room (ER) visit or hospitalization. |
| Evaluation of baseline and diagnostic electroencephalograms | up to 8 months | Both baseline and diagnostic electroencephalograms (EEG) will be obtained with patient consent from hospitals within the United States. An epileptologist will review de-identified EEG recordings to identify and classify abnormalities using a predetermined scoring system. |
| Examine the association between brain MRI structural abnormalities and EEG findings | up to 11 months | Compare the frequency of various grades of brain MRI abnormalities in individuals with LAMA2-MD with and without seizures. Identify any association between MRI abnormality and type of seizure. |
Countries
United States
Outcome results
None listed