Hanalise V. Huff, MD, MPH, and Kenneth R. Huff, MD
A 6-month-old girl is brought to the office because she no longer reaches for her toys. The pregnancy was full term, but the mother remembers that the fetal kicking was less than with an older brother. Delivery was uncomplicated, and the newborn fed well from birth. The girl began to show visual attention at 2 to 3 weeks, smiled socially at 1 month, and pushed up while prone at 2 months. Although she turned over at 4 months, she has not done this in the past month. She no longer reaches up to the mobile over her crib.
On physical examination, the girl lies quietly on the table and watches the examiner intently. Her growth parameters, including head circumference, are normal. After she has been undressed, it is apparent that she exhibits “see-saw” breathing (ie, abdomen rises with inspiration) and has a frog-leg posture (ie, batra-chian position). The cranial nerve examination is normal except for head-turning strength. When she is pulled t a sitting position, her head lags far behind and her arms are straight at the elbows. She cannot raise her arms off the table. When a rattle is placed in her hands, she manipulates the toy, which she regards from the corner of her eye. Deep tendon reflexes are absent, but her pain sensation is intact.
1. What is meant by hypotonia?
2. How is the level of nervous system involvement determined in infants with hypotonia?
3. What is the significance of a loss of developmental milestones or abilities?
4. When are diagnostic tests appropriate for a child with hypotonia?
5. How are clinical management issues related to prognosis?
Infants with decreased tone are referred to as hypotonic or “floppy.” Hypotonia is most simply defined as lower than normal resistance to passive motion across a joint but is also suggested by abnormal posture. Although the lack of resistance may have other components (eg, connective tissue abnormalities suggested by an unusual range of joint mobility and hyperelastic skin, features of Ehlers-Danlos syndrome, features of Down syndrome), muscle strength is a key component. Tone can be used as a surrogate indicator of strength in infants who cannot cooperate with resistance testing. Weakness can also be inferred from functional observations and the inability to sustain limbs against gravity or the lack of a withdrawal response of a limb to a painful stimulus. Identification of the affected central nervous system (CNS) level (eg, upper motor neurons, lower motor neurons, spinal cord, anterior horn cell, peripheral nerve components, myoneural junction, muscle fibers) is most important in determining the etiology of hypotonia in infants and children. Only after this localization is the likely pathology defined in most cases.
Hypotonia is not unusual in neonates, and non-neuromuscular causes of hypotonia are more common than neuromuscular conditions. Non-neuromuscular causes include hypoxic-ischemic encephalopathy and brain lesions related to preterm birth, such as intraventricular hemorrhage and periventricular leukomalacia. Genetic abnormalities also are frequently present shortly after birth. Spinal muscular atrophy (SMA) is a common progressive genetic condition with a prevalence similar to that of cystic fibrosis (approximately 1 in 5,000). Duchenne muscular dystrophy (DMD), which manifests between ages 2 and 5 years, is the most common neuromuscular condition in childhood, with a prevalence of 1 in 1,700 to 1 in 3,500 male births. The DMD gene has been found to spontaneously mutate in approximately 50% of patients. Among non–genetically acquired disorders, the prevalence of acute postinfectious polyneuritis (ie, Guillain-Barré syndrome) is 2 to 8 per 100,000.
Hypotonia in infants often presents with unusual posture, diminished resistance to passive movements of the limbs or trunk, or an excessive range of joint mobility. Infants with hypotonia have delayed motor milestones, decreased movements, and poor head and trunk control (Figure 128.1). Older children may have decreased ability to resist with strength testing of individual muscle groups as well as impaired functional strength in sitting, standing, walking, climbing, or running (Box 128.1). Swayback posture in standing may be indicative of hip girdle or proximal weakness. Pointed toes in the supine position may be indicative of an upper motor cause.
Figure 128.1. Traction maneuver. The arms are completely extended, head control is poor, and the legs are abducted at the hip.
Box 128.1. Diagnosis of Hypotonia in the Pediatric Patient
•Decreased resistance to passive movement of a joint
•Muscular weakness in older children
•Etiologic diagnosis related to the nervous system level of the lesion
Tone is a product of connective tissue structural elements, including ligaments, tendons, and joint capsules; muscle fiber number and integrity; and nerve fiber input to muscle. Nerve input to the muscle includes the number and myelination of axon fibers, trophic factors from the nerve, and frequency of action potentials depolarizing the muscle membrane. The control of tone through the anterior horn cells is complex and involves more than just the corticospinal tract (upper motor unit) but also other descending tract influences. Lesions of the neuromuscular apparatus (lower motor unit), which includes muscle, nerve, nerve sheaths, and anterior horn cells, can most directly decrease tone; however, lesions of any of the other structures at many levels of the nervous system also can affect tone. The final common pathway of upper or lower motor unit modification of tone is through the gamma loop, which is part of the fusimotor system. The fusimotor system consists of gamma motor neurons within the anterior horn of the spinal cord innervate the contractile muscle portions on each end of the intrafusal fiber and enhance the sensitivity of the sensory endings to stretch, which in turn transmit signals back to the alpha motoneurons in the anterior horn, thereby innervating the rest of the muscle. Different CNS levels (ie, motor cortex, thalamus, basal ganglia, vestibular nuclei, reticular formation, cerebellum) can modify tone through their effect on the gamma loop motor neuron.
The nature of the lesion at different levels of the nervous system may be quite variable. For example, ultrastructural abnormalities occur in congenital myopathies, including those related to respiratory chain defects; anterior horn cell apoptosis occurs in SMA and may also occur with ischemic insults; stripping of myelin by macrophages occurs with acute postinfectious polyneuritis; and muscle voltage-gated channels are involved in periodic paralyses.
Distinguishing clinical features in determining the level of the lesion in the nervous system includes pattern of weakness, activity of deep tendon reflexes, presence of fasciculations or sensory loss, cerebrospinal fluid findings, serum muscle enzyme levels, electromyography (EMG) pattern, nerve conduction studies, and histologic appearance or assays of the muscle or nerve biopsy. When assessing the child with hypotonia it is useful to separate first upper motor neuron or brain causes from neuromuscular causes (Table 128.1). The former includes perinatal hypoxia-ischemia, intracranial hemorrhage, and cerebral dysgenesis. These problems may present with hypotonia in infancy but later are evident as a static encephalopathy. A child with a CNS cause may have a below-normal level or range of attention and may lack age-appropriate social skills. Seizures or hemiparesis also signify a likely CNS cause. In an older child, fine motor coordination, quality and repertoire of movements, and language may be affected. The deep tendon reflexes may be brisk or easily elicited. The Babinski reflex may be dorsiflexor. In infants, fisting of the hands, scissoring of the extended legs on vertical suspension, and movement through postural reflexes, such as the asymmetric tonic neck reflex, are clues to an upper motor neuron process. In a patient with an upper motor neuron lesion, serum muscle enzymes, EMG, nerve conduction studies, and muscle biopsy are all normal. However, the child with 1 of the neuromuscular causes for hypotonia, including congenital myopathy, SMA, muscular dystrophy, and acute postinfectious polyneuritis, that does not also involve brain or facial nerves or muscles may have an interested and visually attentive facial appearance. This may be the case even in the presence of severe weakness that allows only sparse or nearly absent limb movements. With many of these neuromuscular lesions, deep tendon reflexes may be difficult to elicit or may be absent.
Older children may display a different pattern of weakness that is suggestive of the level of involvement. If the weakness is preferentially in the upper extremity extensor and lower extremity knee flexor, ankle dorsiflexor, and ankle evertor muscle groups (ie, anti-gravity muscles), the lesion likely involves the upper motor neuron. Static bilateral hemiparesis is suggestive of severe hypoxemicischemic insult, and in the child who was born preterm, diplegia is suggestive of periventricular leukomalacia. A differential weakness in opposing muscle groups resulting from CNS causes may be present and contribute to hypotonia for a long period before spasticity intervenes and increases tone. If the weakness involves agonist and antagonist muscles equally across a limb joint, however, it probably represents a neuromuscular process. It is also important to remember that hypotonia can result from disorders with combined lesions in levels above the lower motor neuron and in the motor unit. Examples include Krabbe disease, glycogen storage disease type 2 (ie, Pompe disease), congenital myotonic dystrophy, mitochondrial and peroxisomal disorders, and hypoxic-ischemic insults involving the upper motor neuron and anterior horn cell.
|Table 128.1. Exemplified Differential Diagnosis of Infantile Hypotonia by Nervous System Level|
Static encephalopathy related to perinatal or prenatal insults
Dysgenesis (eg, Down syndrome, Prader-Willi syndrome)
Degenerative conditions (eg, storage disease)
Dysraphism or other malformation
Anterior horn cell
Spinal muscular atrophy
Arthrogryposis multiplex congenita
Hereditary sensorimotor neuropathy type 3
Acute polyneuritis (rarely occurs in infancy)
Myasthenia gravis (transient or congenital)
Toxin (botulism or aminoglycoside antibiotics)
Congenital structural myopathy (ie, nemaline, central core, myotubular, multicore, congenital fiber-type disproportion)
Congenital myotonic dystrophy
Congenital muscular dystrophy (eg, Fukuyama type, Walker-Warburg syndrome, muscle eye brain disease, merosin-deficient myopathy)
Mitochondrial myopathy (cytochrome-c oxidase deficiency)
Aminoacidopathy and organic acidemia, hypercalcemia, renal tubular acidosis, rickets, celiac disease, hypothyroidism, collagen disease, congenital heart disease, glycogen storage disease (eg, Pompe disease), carnitine deficiency, peroxisomal disorders)
A methodical assessment using clinical and laboratory features in children to localize the lesion to a particular nervous system level can help anatomically narrow a wide differential diagnosis (Table 128.2).
Particular aspects of the history are especially important (Box 128.2). Strength of fetal movements relative to other pregnancies and ischemic, toxic, metabolic, or infectious fetal exposures should be ascertained. Relatively decreased fetal movements may signify an early degenerative condition. Polyhydramnios can signal prenatal weakness in swallowing. Birth events should be investigated for sources of possible insults to the neonatal nervous system, such as preterm status or birth asphyxia. The physician should determine whether any of the child’s developmental skills have been lost. Any associated loss of tone or strength could signify a progressive condition rather than a static problem, such as would occur with a birth injury. The acuity of the developing weakness is another important clue in the differential diagnosis. Rapid-onset hypotonia accompanied by constipation, poor feeding, and other bulbar involvement may be suggestive of botulism. Acute losses of tone and strength may also occur with enteroviral poliomyelitis, Guillain-Barré syndrome, myasthenia, and myositis. Relapsing-remitting courses of hypotonia may occur with myasthenia; metabolic myopathies, including mitochondrial dis-orders; and periodic paralysis in the older child. The child who has recently been hiking should be evaluated for tick paralysis. A parallel deterioration in intellectual functions or seizures may be indicative of leukodystrophy, storage disorder, or another degenerative disorder, including 1 of the several types of Leigh disease, particularly if ataxia, brain stem symptoms, and respiratory dysfunction subsequently occur.
Box 128.2. What to Ask
•Were the fetal movements of the child abnormal or less than those of previous pregnancies?
•Was the pregnancy full term? Was the delivery complicated?
•Does the mother, do any siblings, or do other family members suffer from a similar weakness?
•Has the child lost any developmental skills? Is the problem getting worse?