DMCRN-02-001: Assessing Pediatric Endpoints in DM1

Milestone Assessment using Peabody definitions: This survey would ask parents to assess the age of motor milestones in days, months of infant age. Birth history, including prematurity, ventilatory status, and feeding problems would also be collected on the CRF. Feeding and ventilatory support, as well as height and weight will be collected at each study visit.

A blinded, standardized video assessment tabulating language milestones by a trained rater will be conducted at each visit.

The Vineland will be administered by an interviewer to ensure standardized intake of data. This assessment will capture the adaptive function, including gross motor and fine motor, as reported by the parent proxy.

The congenital and childhood myotonic dystrophy health index is a disease specific patient or proxy reported outcome measure specific to these conditions. The current study will utilize the proxy version.

This assessment asks parents for global impression of change related to the baseline visit and will be used as an anchoring measure for the statistical analyses.

The GMFM assesses functional abilities like lying/rolling, sitting, crawling/kneeling, standing, and walking, running, and jumping.

Fine needle muscle biopsy:On the baseline visit, a fine needle aspirate will be performed. Biopsy will only be peformed once to minimize the risk. The procedure will be performed with local anesthesia (1% lidocaine without epinephrine and free of preservatives) of the vastus lateralis. Following lidocaine injection, a fine needle will be used to aspirate the quadriceps muscle to obtain a total of one aspirate. The aspirate will be flash frozen in liquid nitrogen. A similar procedure has been performed on adults with DM1, and the average biopsy yields sufficient tissue for RNA-Seq analysis.

DNA and RNA samples will be processed by Virginia Commonwealth University.

Lean muscle mass will be evaluated using serial DEXA scans as an exploratory endpoint. All sites will use a Hologic DEXA scanner. Investigators will evaluate whole body lean mass, left and right arm lean mass, and left and right leg lean mass. Particularly early in childhood, investigators would expect rapid changes in lean muscle mass. If there were a divergence between controls and subjects with CDM, this would provide evidence that CDM is a disorder of muscle maturity, as well as provide a potential biomarker.

The WHO Motor Milestones is a set of 6 standardized motor milestones that include 1) Sitting without support, 2) Standing with assistance, 3) Hands-&-knees crawling, 4) Walking with assistance, 5) Standing alone, and 6) Walking alone.