Objective: To diagnose and elucidate the underlying disease mechanism in patients with neuromuscular and neurogenetic disorders with congenital or pediatric onset (phase 1 of the protocol) and to study the natural history and mechanism of disease in neuromuscular and neurogenetic disorders of childhood (phase 2 of the protocol). Study population: Patients with childhood onset neuromuscular and neurogenetic disorders, their affected and unaffected family members, and healthy volunteers. Patients with later onset of a disorder that is known to typically have childhood onset will be included as well. Design: Diagnostic and prospective longitudinal natural history study. Outcome Measures: Diagnose and characterize patients with neuromuscular and neurogenetic disorders with congenital or pediatric onset and study the natural history and underlying disease mechanism. In the characterized patient population identify and develop effective outcome measures for use in future clinical trials, including applicable motor scales, quality of life scales, biomarkers from blood and urine, imaging studies, and pulmonary function tests.
- INCLUSION AND EXCLUSION CRITERIA: Probands inclusion criteria Phase 1: 1. Aged 4 weeks and older 2. Documentation of a personal history of a childhood-onset, hereditary/familial, neurological disorder or later onset of a disease that more commonly has childhood onset. Acceptable documentation includes evaluation through any or all of the following evaluations done prior to enrollment. 1. Medical history, including family history information 2. Physical examination 3. Muscle, nerve, or skin biopsy 4. Magnetic resonance imaging (MRI) 5. Electromyography (EMG) 6. Nerve conduction study (NCS) 7. Electroencephalogram (EEG) 8. Muscle ultrasound 9. Genetic, metabolic, or other laboratory testing such as increased serum Creatine Kinase (CK) and abnormal serum lactate/pyruvate ratio. Exclusion criteria for probands Phase 1: 1. Individuals who are unable or unwilling to be examined 2. Minors who do not hve a parent or guardian able to provide informed consent 3. Adults seen offsite who are unable to provide their own consent Probands inclusion criteria Phase 2: 1. Aged 4 weeks and older 2. Documentation of a defined childhood onset neuromuscular and neurogenetic disorders through phase 1 testing. Exclusion criteria for probands Phase 2: 1. Individuals who are unable or unwilling to be examined. 2. Adults who are unable to provide their own consent and who have not previously appointed an individual with Durable Power of Attorney (DPA) or who are unable to appoint a DPA or guardian. 3. Minors who do not have a parent or guardian able to provide informed consent. 4. Adults seen offsite who are unable to provide their own consent. Unaffected Family members - Inclusion Criteria: 1. Unaffected family members must be related by blood to a proband enrolled in the study. Biological relations may include first (parent or sibling), second (grandparents, aunts, uncles, half siblings) and third degree relatives (cousins). 2. Age 4 weeks and older. Unaffected Family members - Exclusion Criteria: 1. Individuals whom are unable or unwilling to be examined. 2. Family members who are showing symptoms of the familial neurogenetic or neuromuscular condition (these may be enrolled as probands). 3. Neonates. 4. Adults who are unable to provide their own consent. Healthy Volunteers - Inclusion Criteria: 1. Must be unaffected by a neurological condition. 2. Willing and able to comply with all protocol requirements and procedures, including MRI without sedation and without contrast. 3. Able to give informed assent and parent(s)/legal guardian to give informed consent in writing signed by the subject and/or parent(s)/legal guardian. Healthy Volunteers - Exclusion Criteria: 1. Healthy volunteers who have metal objects in their body that are not MRI-safe. These include the following objects: 1) pacemakers or other implanted electrical devices; 2) brain stimulators; 3) some types of dental implants; 4) aneurysm clips (metal clips on the wall of a large artery); 5) metallic prostheses (including metal pins and rods, heart valves, and cochlear implants; 6) implanted delivery pump; 7) permanent eye liner; or 8) shrapnel fragments. 2. Healthy volunteers who have a fear of closed spaces. 3. Neonates. 4. Pregnant