Tone opposes gravity and maintains postural attitude. The term hypotonia refers to a state of low muscle tone. Infants who are hypotonic are often referred to as floppy because their limbs and head hang limply rather than firmly extended when held by an examiner in the prone position. These infants also may show a diminished resistance to passive limb movement when examined. The floppy infant seems to be weak, but the examiner may find it difficult to distinguish between true weakness and apparent weakness due to hypotonia and/or hyperlaxity.

Causes for hypotonia in infants are many, and it is the responsibility of the clinician to create a relevant differential diagnosis for the clinical presentation (Fig. 136.1). The clinician should first focus on the presenting history, noting weeks of gestation, intrauterine drug exposure, perinatal ultrasound abnormalities (e.g., cerebral dysgenesis, reduced fetal movements, oligohydramnios, or polyhydramnios), intrauterine infections (herpes simplex, cytomegalovirus, toxoplasmosis, rubella), and perinatal drug exposure or trauma (global or focal). A notation also should be made on whether the infant had low tone, limb contractures, difficulty breathing, or a weak cry at birth. This information helps determine whether the condition began before, at, or after birth. Hypotonia, emerging days after birth suggests an inborn error of metabolism. Additional history, when evaluating an infant in the first month of life, should include the strength of the infant’s suck and whether the infant chokes with feeds. Potential exposures to Clostridium botulinum (via honey or corn syrup consumption or dirt) are important. Family history may reveal an inherited risk for hypercoagulability (including prior maternal spontaneous abortions), immune-mediated conditions, genetic syndromes (premature death may suggest a metabolic syndrome), neuropathies, myasthenia gravis, or myopathies/muscular dystrophies (developmental delay and weakness).

The aforementioned history will complement a careful neurologic exam that identifies (1) unique dysmorphic features; (2) a highly arched palate or tenting of the mouth (suggestive of congenital tongue weakness); (3) respiratory distress; (4) heart, abdominal, genitourinary, skin (birthmarks, doughy quality), or musculoskeletal abnormalities (congenital scoliosis, kyphosis, contractures, hip dysplasia, torticollis, hyperextensibility of joints); (5) level of alertness; (6) quality of cry; (7) cranial nerve dysfunction (facial weakness, ptosis, limited extraocular movements, tongue fasciculations, tongue atrophy, strength of suck); (8) focal or diffuse weakness; (9) evidence of hypertonicity (increased jitteriness and rigidity of the limbs) or hypotonicity (frog-legged posture while supine, lack of spontaneous movement, scarf sign, tendency to keep the trunk flexed while held in horizontal suspension, slip through); and (10) tendon reflex responses. The pertinent findings on examination, in conjunction with a thorough history, will guide the clinician to whether the infant’s presentation is related to a nonneurologic (structural, toxic, or genetic syndrome) or neurologic etiology that may be central (brain and spinal cord) or peripheral (peripheral nerves, neuromuscular junction, or muscle).

If the clinician believes that the hypotonia is neurologic and central in nature, additional workup would include brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan), electroencephalography (EEG), and cerebrospinal fluid (CSF) studies. If the hypotonia is neurologic and peripheral, confirmatory studies may include electromyography (EMG), nerve conduction studies (NCS), serum creatine kinase (CK) levels, muscle ultrasound or MRI, and muscle and/or nerve biopsy. If the findings from these tests raise concerns for a dystrophy or myopathy, additional processing of the muscle for electron microscopy (to identify distinctive ultrastructural abnormalities), immune staining, or biochemical assays for specific enzyme deficiencies should be performed.

If the clinician finds that the hypotonia is nonneurologic, confirmatory diagnostic workup should address a particular genetic syndrome (chromosomal microarray, whole exome sequencing, or targeted gene sequencing), inborn error of metabolism (blood studies—e.g., glucose, electrolytes, blood gas, ammonium, lactate and pyruvate, carnitine profile, liver function testing, very longchain fatty acids, plasma amino acids, 7-dehydrocholesterol, isoimmune electrophoresis for transferrin; urine studies—e.g., urinalysis, urine amino acids, urine organic acids; CSF studies— e.g., amino acids, lactate, pyruvate, neurotransmitters, pterins, and 5-methyltetrahydrofolate), or structural abnormality (bone films, spinal MRI). These studies complement the newborn screening.

Central hypotonia refers to decreased tone due to lesions above the anterior horn cells of the spinal cord. Such hypotonia is often symmetric and affects the upper and lower limbs equally. It may also present with additional features of developmental delay (speech, motor, or global), seizures, and/or brisk reflexes.

Peripheral hypotonia refers to disorders of the motor unit/anterior horn cell, peripheral nerve, neuromuscular junction, and/or muscle. Identifying whether or not there is focality to the weakness often helps with diagnosing its etiology.