What Are Some Initial Evaluations for Suspected Congenital Muscle Diseases?

Patient Presentation
A term male infant was transferred from an outside hospital at 8 hours of life to a regional children’s hospital because of poor tone, poor feeding and an elevated creatinine kinase. He was born to a G1P1 mother with appropriate prenatal care. He had been started on antibiotics after blood and urine were obtained. A lumbar puncture was attempted but no fluid was obtained. The family history was negative for any known congenital or neurological problems.

The pertinent physical exam showed normal vital signs, weight of 3.560 kg (50%), head circumference of 34.5 cm (25%), and length of 52 cm (50-75%). Ballard score was consistent with 38 week gestation. He appeared floppy with arms and legs lying more to the side, and he would have poor respiratory effort intermittently. Respiratory pressure support was being provided to the infant. Anterior fontanelle was soft and flat. There were no obvious facial or other dysmorphic features. Skin showed congenital dermal melanocytosis on the sacrum. His heart, lung, abdomen and genitourinary examinations were normal. Neurologically he had poor tone and muscle weakness in the upper and lower extremities. He appeared to respond appropriately to sounds and lights and would look briefly at the examiner. His suck was poor but his gag reflex was intact. He would attempt to do appropriate newborn reflexes but they were poorly performed due to hypotonia and weakness.

The diagnosis of a newborn infant with poor tone and muscle weakness was made. The patient’s clinical course showed that he had some improvement in his physical examination over the next couple of days but still continued with hypotonia and weakness. The respiratory support continued but was slowly weaning. His creatinine kinase also continued to be elevated while other laboratory testing was normal including cultures at day 3. Magnetic resonance imaging of the brain was normal. The neurologist started to discuss additional potential evaluations and their timing with the neonatologists and family.

Usually congenital myopathies (CM, e.g. nemaline, core, centronuclear myopathies, etc.) and congenital muscular dystrophy (CMD, e.g. LAMA2-related, collage VI-related, alpha-dystroglycan-related muscular dystrophy, etc.) have been diagnosed based on physical examination and histopathology. Traditionally CMs are due to problems with the muscle contractile apparatus and structures that assist excitation-contraction coupling. CMD are due to problems with the extracellular matrix, muscle membrane and sarcolemmal membrane. Differentiating between CM and CMD have become more blurred as genetic testing and additional research and testing becomes available, and these entities have more overlap in these evaluations. Evaluation, diagnosis and management requires a multidisciplinary team to care for the infant and educate and support their family.

Infants with both CM and CMD usually present with hypotonia and muscle weakness which can cause early feeding problems and possibly respiratory problems. Physical examination findings can be subtle and can change with time. Suspicion of a muscle disease is important for starting the evaluation process and including specialists especially neurologists. Causes of muscle weakness with and without hypotonia can be found here, and hypotonia in infants can be reviewed here.

Learning Point
As with many evaluations, non-muscle related problems need to be considered and ruled in or out. For example, hypothyroidism, hypocalcemia and hypomagnesemia can cause hypotonia, and infection can present in many ways. Botulism is not very common but presents with hypotonia and muscle weakness. Having a suspicion for a muscle disease begins the evaluative process with inexpensive, easily available testing such as creatinine kinase and neuroimaging.

Creatinine kinase (CK) is found in muscles but also in the brain and heart. CK elevation usually indicates some type of muscle injury such as overexertion or rhabdomyolysis and generally returns to normal within 24-48 hours. Causes of rhabdomyolysis can be reviewed here. Newly born infants can have normal CK elevation but again they decline to normal after about 4 days. Persistent CK elevations in newborns is usually abnormal but is not specific for a particular muscle disease. Some muscle diseases may also have normal CK levels. If the CK remains elevated then neuroimaging is often the next step.

Neuroimaging, usually with a brain MRI, assists in determining if there are structural abnormalities and/or ventriculomegaly, or other problems such as changes associated with hypoxic-ischemic encephalopathy. Specific structural changes and no ventriculomegaly may lead to considering CMD or other specific genetic testing for the structural abnormality seen. Normal study or ventriculomegaly may lead to more testing by nerve conduction testing or electromyelography. Neurological evaluation is usually needed to gather and interpret data including potential nerve conduction testing, electromyelography, muscle biopsy and genetic testing. Each of these evaluations have advantages and disadvantages and may not be 100% diagnostic. Therefore a neurologist leading this evaluation is important given the costs, invasiveness and the difficulties there can be with test interpretation.

Questions for Further Discussion
1. What temperature should food be cooked to prevent botulism? A review can be found here
2. What specialists might an infant with a muscle disease need to have services from?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Muscle Disorders and Neuromuscular Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Mary P, Servais L, Vialle R. Neuromuscular diseases: Diagnosis and management. Orthop Traumatol Surg Res. 2018;104(1S):S89-S95. doi:10.1016/j.otsr.2017.04.019

Butterfield RJ. Congenital Muscular Dystrophy and Congenital Myopathy. Continuum (Minneap Minn). 2019;25(6):1640-1661. doi:10.1212/CON.0000000000000792

Harmelink M. Differentiating Congenital Myopathy from Congenital Muscular Dystrophy. Clinics in Perinatology. 2020;47(1):197-209. doi:10.1016/j.clp.2019.10.005

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa