Early onset (childhood) monogenic neuropathies
Pierre Landrieu1, Jonathan Baets
1Department of Pediatric Neurology, CHU Paris sud, Hôpital Bicêtre, Paris, France.
Handbook of Clinical Neurology
|August 13, 2013
Summary
Childhood-onset hereditary neuropathies (HN) are classified by clinical signs, genetics, and electrophysiology. Differentiating secondary causes and identifying primary motor sensory neuropathies are key for diagnosis.
Area of Science:
- Neurology
- Genetics
- Pediatrics
Background:
- Hereditary neuropathies (HN) in children require precise classification based on clinical presentation, electrophysiology, and genetic transmission.
- Distinguishing between secondary (metabolic) and primary neuropathies, as well as syndromic versus nonsyndromic forms, is crucial in pediatric cases.
- Autosomal recessive forms and syndromic presentations are more common in childhood-onset HN.
Purpose of the Study:
- To outline the classification and diagnostic considerations for hereditary neuropathies presenting in childhood.
- To highlight the importance of differentiating various HN subtypes, including motor sensory, motor, and sensory/dysautonomic forms.
- To emphasize the genetic heterogeneity and the role of specific genes in diverse HN phenotypes.
Main Methods:
- Classification based on clinical presentation, electrophysiological findings, and genetic transmission patterns (autosomal dominant, autosomal recessive).
- Distinguishing primary neuropathies from those secondary to generalized metabolic disorders.
- Review of genetic heterogeneity and specific gene associations for different HN subtypes.
Main Results:
- Primary motor sensory neuropathies, particularly demyelinating autosomal dominant forms (CMT1), are most frequent.
- Autosomal recessive spinal muscular atrophies and hereditary motor neuropathies (<10% of HN) show significant clinical and genetic diversity.
- Over 40 genes are implicated in primary HN, with many exhibiting varied phenotypes and transmission modes.
Conclusions:
- Accurate classification of childhood-onset HN is essential for identifying specific monogenic disorders.
- Systematic approaches, including ruling out metabolic disorders and considering syndromic forms, guide diagnosis.
- The genetic landscape of HN is complex, with numerous genes contributing to diverse clinical presentations.
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