Saturday, September 30, 2017

Approach to Genetic Disorders Presenting with Infantile Hypotonia



Etiology

Hypotonia is a nonspecific sign that may be caused by a wide variety of etiologies.
Dysfunction in any component of the central or peripheral nervous system can cause hypotonia, including diseases of the muscle, neuromuscular junction, nerves, spinal cord, brain stem, cerebellum, basal ganglia, and cerebrum. Central hypotonia with peripheral spastic hypertonia is highly suggestive of central nervous system (CNS) involvement.

Clinical Presentation
Historical features supporting a genetic etiology include family history of neuromuscular disease, parental consanguinity, and a prior affected sibling. However, the absence of these features does not rule out a genetic cause.
Contractures in the newborn indicate prenatal onset but do not suggest a single, specific diagnosis.
Additional features that may indicate an underlying syndrome may not be present at a young age or may be difficult to appreciate in the neonate or infant.
Laboratory Studies
Several tests are recommended in the evaluation of a child with hypotonia and concern for a genetic disorder.
  • Blood tests: methylation studies for Prader-Willi and Angelman syndromes, creatine kinase, lactate and pyruvate, serum/plasma amino acids, comprehensive metabolic panel, karyotype (if normal, perform chromosomal microarray analysis), very long-chain fatty acids quantification, SMN molecular analysis (if reflexes absent), andmyotonic dystrophy molecular analysis. Consider leukocyte lysosomal enzyme panel.
  • Urine tests: organic acids. Consider mucopolysaccharidosis screen.
  • Other tests: electromyogram, nerve conduction studies, electrocardiogram, echocardiogram, brain MRI, and abdominal and pelvic ultrasound
Treatment
Confirming a genetic diagnosis may affect the treatment regimen and allow parents to more fully understand the child’s clinical course.
Treatment often involves physical therapy and providing methods that support the child, such as splints, braces, or assistive devices. In a few conditions, such as Pompe disease, enzyme replacement therapy is used to treat the underlying disorder and can improve all of the patient’s symptoms.

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