Retrospective Natural History Study of Infants and Toddlers With LAMA2-CMD
Condition: Merosin Deficient Congenital Muscular Dystrophy
MeSH terms: Muscular Dystrophies
Study type: Observational

Summary: 
      This retrospective chart review study of 75-120 LAMA2-CMD patients will expand the
      investigators understanding of the natural history of this disease. Current and pending
      publications cover research performed only in ages 5-16 years; there is currently no
      documented natural history for patients ages 0-5 years. Data collected in this study has the
      potential to inform the design of future interventional studies that draw nearer to clinical
      trial readiness every day.
    

Detailed description: 
      LAMA2-related congenital muscular dystrophy (LAMA2-CMD) is caused by a deficiency of the α2
      subunit of laminin due to mutation of the LAMA2 gene.

      Typical LAMA2-CMD cases present with prominent hypotonia and weakness in infancy. Congenital
      contractures are a common finding in the hands and feet. Weakness and contractures are slowly
      progressive, and most patients do not achieve independent ambulation. Facial weakness and jaw
      contractures disrupt normal feeding, resulting in failure to thrive. Most patients require
      nutrition support at an early age. Cardiac involvement is rare. In addition to neuromuscular
      aspects of the disorder, patients with LAMA2-CMD have central nervous system findings
      including prominent T2 and fluid-attenuated inversion recovery (FLAIR) abnormalities in the
      white matter on brain MRI. Despite the prominent changes on MRI, cognitive function is
      normal, although patients are at risk of seizures, which are seen in 30% of patients.

      A number of potential therapies are currently in development for LAMA2-CMD. A larger
      prospective natural history was conducted at the National Institutes of Health in LAMA2-CMD
      patients, ages 5-16 years of age, testing and validating a wide variety of outcome measures
      suitable for use in clinical trials. However, appropriate clinical outcome measures in
      younger patients (ages 0-5 years) have yet to be validated.

      Some treatments currently in development will almost certainly be more effective the earlier
      the treatment is administered. Given that there is a distinct lack of data for affected
      individuals less than 6 years of age, this study will be instrumental in building outcome
      measures appropriate in younger patients. In order to obtain regulatory authorization to
      launch clinical trials in affected individuals less than 6 years of age, a documented natural
      history for this age group must be demonstrated.

      The primary objective of this study is to characterize aspects of LAMA2-CMD in ages 0-5 years
      through medical chart review/data extraction, and participant survey. This study aims to
      derive clinical trial endpoints useful in conducting interventional trials in the near
      future.

      The secondary objectives of this study include identifying potential prognostic variables of
      LAMA2-CMD, identifying adverse events associated with LAMA2-CMD that warrant monitoring and
      potential preventative measures, and to grow the knowledge base of care standards and
      optimization to improve the patient's quality of life.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Infants and toddlers affected by LAMA2-CMD
      
Keywords: LAMA2; LAMA2-CMD; CMD; MDC1A; LAMA2-MD; Merosin Deficient