Approach to hypotonia (newborn and infant): Clinical sciences

Hypotonia, or decreased muscle tone, is characterized by poor movement and posture control or delayed motor skills. Newborns or infants with hypotonia are often described as “floppy”. You can categorize hypotonia as conditions affecting the central or peripheral nervous system.

If a pediatric patient presents with hypotonia, perform an ABCDE assessment to determine if they are stable or unstable. If unstable, stabilize the airway, breathing, and circulation, and consider intubation if necessary. Obtain IV access, consider giving IV fluids, begin continuous vital sign monitoring, and provide supplemental oxygen if needed. Finally, consider a full sepsis workup and antibiotics for newborns, since hypotonia might be related to sepsis.

When it comes to stable patients, your next step is to obtain a focused history and physical examination. There are a few things you should look out for. Generally, these patients present with motor delay. It is also important to determine if hypotonia was present at birth or developed progressively, as this will be a clue to the cause. Be sure to assess for clues of central nervous system (CNS) involvement like seizures, cognitive, vision, or hearing issues. Next, assess if there is upper or lower motor neuron involvement.

As a reminder, upper motor neuron lesions will present with spasticity and hyperreflexia, while lower motor neuron lesions will present with hypotonia and reduced or absent reflexes. Finally, ask about family history.

First, let’s discuss central nervous system etiologies of hypotonia. History might include developmental regression or seizures, while the exam reveals reduced alertness, normal strength, and hyperactive or normal reflexes, as well as the presence of primitive reflexes. Patients may have microcephaly or macrocephaly, and their eyes might not track. They might display hand fisting or scissoring on vertical suspension. With these findings, consider a central nervous system etiology. Obtain brain imaging, like a CT or MRI; an EEG; and a metabolic screen, including a CMP and ammonia level.

Let’s go over your findings, starting with inborn errors of metabolism. Affected newborns are often healthy at birth but develop hypotonia over the first 12 to 24 hours. Physical exam reveals signs suggesting organ dysfunction, like arrhythmias or hepatomegaly. Imaging and EEG are usually non-specific and might be abnormal. Labs commonly reveal hypoglycemia or hyperammonemia, which suggests inborn errors of metabolism.

Next, let’s look at genetic syndromes. If you see syndromic or dysmorphic features with normal brain imaging, EEG, and metabolic screen, consider genetic syndrome. Now, if physical exam findings include flattened posterior occiput, upslanted palpebral fissures, epicanthal folds, flat nasal bridge, protuberant tongue, excess posterior nuchal skin, and a single palmar crease, consider Down syndrome. Next, obtain genetic testing to confirm trisomy 21 and diagnose Down syndrome.

Here’s a clinical pearl! Other trisomies associated with hypotonia include trisomy 13, Patau syndrome; and trisomy 18, Edwards syndrome.

On the flip side, if your patient had early feeding problems but later developed an insatiable appetite, and exam reveals micropenis and cryptorchidism or clitorial and labial hypoplasia, consider Prader-Willi and obtain genetic testing. A deletion of 15q11-q13 confirms the diagnosis.

Here’s a clinical pearl! Fragile X syndrome is a genetic condition that presents with hypotonia during infancy; however, these children aren’t usually diagnosed until 3 to 4 years of age, when learning and developmental disabilities begin. Affected individuals typically demonstrate characteristic phenotypic features, such as a prominent forehead and jaw, large, low-set ears, and macroorchidism in biological males.

Alright, let’s look at functional or structural brain abnormalities. If you see abnormal MRI findings, like signal intensity changes or reduced gyri, an abnormal EEG revealing seizure activity, and a normal metabolic screen, consider a brain abnormality.

First up is hypoxic-ischemic encephalopathy, or HIE, which is caused by perinatal hypoxemia. These infants usually had a difficult delivery and develop poor feeding and seizures. Physical exam revealing autonomic dysfunction, like decreased heart rate with stimuli; and brain MRI demonstrating signal intensity changes, suggest HIE.

Next up are brain malformations. Affected patients initially have hypotonia but gradually develop hypertonia. Exam findings include cranial nerve abnormalities, like impaired eye abduction; Babinski sign; global delay; and micro- or macrocephaly. Imaging confirms a structural brain malformation like lissencephaly, where the cerebral cortex is smooth; holoprosencephaly, where the cerebral hemispheres are not fully separated; and Joubert syndrome, in which the cerebellar vermis is absent or underdeveloped. In these cases, you can diagnose brain malformations.

Finally, let’s go back to our imaging and discuss spinal cord abnormalities. These patients may have a history of breech delivery, and the exam demonstrates a spinal cord-level sensory or motor abnormality. However, imaging, EEG, and metabolic screening are normal. With these findings, consider a spinal cord abnormality and obtain a spine MRI. The presence of abnormalities like myelodysplasia, syringomyelia, arteriovenous malformation, trauma, or tumor; confirms a spinal cord abnormality.

Now, let’s take a step back and talk about peripheral nervous system etiologies of hypotonia. On exam, these patients are alert and respond appropriately to their surroundings, but exhibit profound weakness, hyporeflexia or areflexia, and muscle atrophy. In this case, consider peripheral nervous system etiologies, and obtain a serum creatine kinase level, and electromyography, or EMG.