Hypotonia and weakness may signify a variety of systemic, neurologic, and neuromuscular disorders (Table 120-1). Evaluation of hypotonia and weakness can be challenging, as the list of possible diagnoses is extensive and includes many rare conditions. A logical first step in the evaluation is to localize the lesion to the central nervous system (CNS) or the peripheral nervous system (PNS), which frequently can be accomplished by detailed birth and medical history, along with thorough general and neurological examination. Localization will help to narrow the list of differential diagnoses and guide subsequent investigations to reach a specific diagnosis. It is important that pediatric hospitalists are knowledgeable of the general approach to this group of patients, and have a basic understanding of the diagnostic possibilities and their clinical presentations, pathophysiology, diagnosis, and associated morbid conditions as well as management.
TABLE 120-1Differential Diagnosis of Infantile Hypotonia |Favorite Table|Download (.pdf) TABLE 120-1 Differential Diagnosis of Infantile Hypotonia
Central hypotonia (with upper motor neuron signs)
Brain or spinal cord: hypoxic ischemic injury, trauma, infection, malformations
Metabolic and endocrine etiology: hypothyroidism, Zellweger syndrome, neonatal adrenoleukodystrophy, biotinidase deficiency, mitochondria diseases, aminoacidopathies, organic acidurias, urea cycle disorders, and others
Chromosomal: trisomy 21, Prader-Willi syndrome, and others
Peripheral hypotonia (with lower motor neuron signs)
Anterior horn cell disease: spinal muscular atrophy, infantile neuroaxonal dystrophy, poliomyelitis, polio-like illnesses
Peripheral neuropathy: Riley-Day syndrome, Charcot-Marie-Tooth disease, chronic inflammatory demyelinating neuropathy (CIDP), Guillain-Barre syndrome
Neuromuscular junction defect: transient neonatal myasthenia gravis, congenital myasthenic syndrome, infant botulism, juvenile myasthenia gravis
Muscular dystrophy: congenital myotonic dystrophy, congenital muscular dystrophy
Metabolic myopathies: glycogen storage disease type II (Pompe), mitochondrial cytopathy
Congenital myopathy: nemaline myopathy, myotubular myopathy, central nuclear myopathy, central core myopathy, congenital fiber type disproportion, and others
Connective tissue: collagen VI disease (Ullrich muscular dystrophy)
CNS (or upper motor neuron [UMN]) diseases affect the neural pathway at any point from their origin in the cortex to above the anterior horn cells of the spinal cord or motor nuclei of the cranial nerves. PNS (or lower motor neuron [LMN]) diseases are further localized to the anterior horn cells, spinal roots, brachial or lumbosacral plexus, peripheral nerves, neuromuscular junctions, or muscle fibers. Overlap occurs in processes that affect both central and peripheral myelin, such as metachromatic leukodystrophy, or those that involve multiple tissues, as in mitochondrial disease or myotonic dystrophy.
An infant or a child presenting with weakness or hypotonia requires a thorough history and a comprehensive physical and neurological examination. Initial symptoms vary by age at presentation. During neonatal period and infancy, patients frequently present with poor tone (i.e. “floppy”) or with delay in achieving developmental milestones. In older children, the most common complaints relating to weakness include an unusual gait, frequent falls, inability to run or climb stairs, inability to keep up with ...