Genetic evaluation of the pediatric patient with hypotonia: Perspective from a hypotonia specialty clinic and review of the literature

Aim Hypotonia is a symptom of diminished tone of skeletal muscle associated with decreased resistance of muscles to passive stretching, which can be caused by abnormalities of the central nervous system, any element of the lower motoneuron, or both. Hypotonia is not a specific diagnosis, but can be part of over 500 different genetic disorders, with many other conditions waiting to be identified. This review proposes a pragmatic approach to evaluating hypotonia in neonatal and pediatric populations by using a diagnostic algorithm. Method We use a dedicated literature review combined with clinical experience in a newly established multidisciplinary center for hypotonia to establish a diagnostic algorithm. Results Hypotonia can be a symptom of over 500 different genetic disorders. It can present as peripheral, central, or combined hypotonia, providing necessity for rational and systematic diagnostic testing. Interpretation Our analyses demonstrate that a staged diagnostic approach categorizing patients as having peripheral, central, or combined hypotonia is the most efficient to providing a rational work-up. Establishing a diagnosis is crucial for prognosis, management, and treatment strategies, and for ascertaining an accurate recurrence risk for future offspring in a family.