retrospective natural history study of infants and toddlers with lama2-cmd

Conditions: Merosin Deficient Congenital Muscular Dystrophy

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.

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.

Eligibility criteria:
inclusion criteria: 1. patients diagnosed with lama2-cmd through: 1. genetic confirmation of two (2) pathogenic mutations in lama2 -or- 2. genetic confirmation of one (1) pathogenic mutation in lama2, and supporting clinical phenotype based on two or more of the following: physical examination, brain imaging, muscle imaging, muscle biopsy, and creatine kinase (ck) levels (blood test) 2. patients may be living or deceased 3. patients may be male or female 4. patients with available medical records between 2000-2017, documenting diagnosis, observation, and treatment between ages 0-5 years and a minimum set of data covering 12-24 months during this age period. 5. patients with medical charts available in english 6. patients (or parents of minor patients) who are able to consent to participation in english or spanish, either directly, or through their own trusted interpreter 7. patients between the ages of 8-17 years who are able to provide assent to participation in english or spanish, either directly, or through their own trusted interpreter exclusion criteria: 1. patients not diagnosed with lama2-cmd 2. patients with no available medical records documenting diagnosis, observation, and treatment between ages 0-5 years 3. patients with medical charts not available in english 4. patients (or parents of minor patients) not able to consent to participation in english or spanish, either directly, or through their own trusted interpreter

Keywords: lama2 lama2-cmd cmd mdc1a lama2-md merosin deficient