The causes of neonatal hypotonia are usually classified as central or peripheral. Central hypotonia may include chromosomal, metabolic and toxic conditions.
Peripheral cause of hypotonia (may impact anterior horn cell, peripheral nerve, neuromuscular junction and/or muscle):
(1) motor neuron and/or nerve disorders (spinal muscular atrophy or SMA, congenital neuropathy)
(2) myopathies (myotonic dystrophy, muscular dystrophy, congenital myopathy, metabolic myopathy, idiopathic)
Central nervous system (CNS) causes of hypotonia:
(1) ischemic (hypoxic-ischemic encephalopathy)
(2) intracranial hemorrhage
(3) brain malformations (agenesis of the corpus callosum, Dandy-Walker malformation, Joubert syndrome, lissencephaly, etc)
Chromosomal abnormalities associated with hypotonia:
(1) Down syndrme (trisomy 21)
(2) Prader-Willi syndrome
(3) Noonan syndrome
(4) other
Metabolic, endocrine and/or toxin-associated hypotonia:
(1) respiratory chain defect disorders
(2) peroxisomal disorders
(3) nonketotic hyperglycemia
(4) methemoglobinemia
(5) hypothyroidism
(6) infantile botulism
The diagnostic approach involves:
(1) an initial complete clinical examination
(2) selected testing based on initial assessment
(3) reserving expensive or low-yield testing as later steps in the process
Based on the initial evaluation the workup should be:
(1) Some metabolic and endocrine conditions can be identified based on laboratory tests or clinical history.
(2) For all other causes neuroimaging and an EEG should be performed.
(3) If dysmorphic features are present, then perform chromosomal studies and targeted genetic testing.
(4) If a peripheral cause is suspected, then perform tests for the more common conditions (spinal muscular atrophy, muscular dystrophy and Prader-Willi syndrome).
(5) Once these tests have been performed and analyzed, then more specific tests should be considered (muscle biopsy, metabolic testing, mutational analysis, EMG, etc).
