The Role of Muscle Biopsy in Diagnostic Process of Infant Hypotonia: From Clinical Classification to the Genetic Outcome

Veneruso, Marco; Broda, Paolo; Baratto, Serena; Traverso, Monica; Donati, Alice; Savasta, Salvatore; Falsaperla, Raffaele; Mancardi, Maria Margherita; Pedemonte, Marina; Panicucci, Chiara; Piatelli, Gianluca; Pacetti, Mattia; Moscatelli, Andrea; Ramenghi, Luca A.; Nobili, Lino; Minetti, Carlo; Bruno, Claudio

doi:10.3389/fneur.2021.735488

Cited by 8 publications

(4 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The decision to conduct a diagnostic workup involving a muscle biopsy for infants with hypotonia is sometimes difficult owing to a few factors, including the general anesthesia required for invasive procedures, the risk of respiratory complications, and occasional non-specific results. Except in cases of spinal muscular atrophy, which is routinely diagnosed through genetic investigations without the need for histopathological results, the roles of a muscle biopsy are to classify the specific disease category, help clinicians choose a genetic test, and/or modify a previous diagnosis [20]. Patients with congenital myopathy present a higher concordance rate between biopsy and genetic findings than those with congenital muscular dystrophies and metabolic myopathies.…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Neurologic Outcomes of X-Linked Myotubular Myopathy

et al. 2022

View full text Add to dashboard Cite

Purpose: X-linked myotubular myopathy (XLMTM) is a rare condition of centronuclear myopathy caused by myotubularin 1 (MTM1) mutations. Patients with XLMTM show different neurodevelopmental outcomes after the neonatal period depending on age and acquired hypoxic damage. We aim to evaluate the clinical characteristics and neurodevelopmental outcomes of patients with XLMTM who were followed up at a single center. It is essential to understand the volume and conditions to prepare for being a candidate for new therapeutic strategies. Methods: Patients diagnosed with centronuclear myopathy by muscle pathology and MTM1 mutation analysis were included. We retrospectively investigated motor milestones, communication skills, and bulbar and respiratory function in the patients. The patients were categorized into two groups: with and without hypoxic insults (HI). Results: All 13 patients were severely affected by neonatal hypotonia and required respiratory support and a feeding tube during the neonatal period. The follow-up duration was 4.4 years (range, 0.3 to 8.9). In the non-HI group, developmental milestones were delayed but were slowly achieved. Some patients underwent training in oral feeding with thickened foods and weaning from ventilation. Patients with HI showed poor motor function catch-up and communication skills. Three deaths were associated with acute respiratory failure.Conclusion: Patients with XLMTM without HI can survive long-term with the slow achievement of motor milestones and bulbar and respiratory function. However, hypoxic brain damage following acute respiratory failure negatively influences their developmental potential or even lead to death. Therefore, parental education for proper respiratory management is necessary, especially for young children.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Neurologic Outcomes of X-Linked Myotubular Myopathy

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Mutations in 12 genes that encode proteins related to the thin filament of the sarcomere have been identified, with NEB and ACTA1 being the most common [ 15 ]. Traditionally, nemaline myopathy is diagnosed by the presence of “nemaline bodies” or “rods” on skeletal muscle biopsy, which appear as small red inclusions arranged in clusters on Gomori trichrome stain [ 16 ]. The role of muscle biopsy in the diagnostic workup of hypotonia is controversial as it is invasive, and the results are not specific and may yield inconclusive results [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Traditionally, nemaline myopathy is diagnosed by the presence of “nemaline bodies” or “rods” on skeletal muscle biopsy, which appear as small red inclusions arranged in clusters on Gomori trichrome stain [ 16 ]. The role of muscle biopsy in the diagnostic workup of hypotonia is controversial as it is invasive, and the results are not specific and may yield inconclusive results [ 16 ]. However, advances in molecular genetic testing offer a non-invasive and more accurate alternative to muscle biopsy, which can be painful and carry risks of complications such as bleeding or infection [ 1 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

Nemaline Myopathy in a Hypotonic Neonate: Diagnostic Approach for Early Detection and Management

Vu,

Nanda,

Chassee

2024

Cureus

View full text Add to dashboard Cite

Neonatal hypotonia presents with low muscle tone and an array of symptoms that vary depending on the etiology. The differential diagnosis for this condition is complex. It is crucial to exclude life-threatening causes before following a diagnostic algorithm and performing additional tests. Given the wide range of clinical symptoms and etiologies for neonatal hypotonia, rapid genetic testing has the potential to expedite diagnosis, reduce invasive testing such as muscle biopsy, reduce hospital stays, and guide condition management. A four-week-old girl was admitted to the emergency department (ED) with a one-day history of lethargy, poor feeding, congestion, cough, and hypoxemia. Given positive rhino-enterovirus testing and high inflammatory markers, antibiotics were administered. Imaging, venous blood gas, and blood cultures were negative, and the patient was admitted to the pediatric intensive care unit (PICU) for hypoxemia. After speech-language pathology (SLP) and occupational therapy (OT) evaluation, weak orofacial muscles and feeding issues resulted in a nasogastric tube placement. A swallow study revealed decreased pharyngeal contraction and post-swallow liquid residue. Laryngoscopy showed mild laryngomalacia and dysphagia with aspiration. Genetic testing identified an ACTA1 mutation and confirmed nemaline myopathy (NM). The patient's oxygen levels dropped further during sleep, resulting in diagnoses of severe obstructive and moderate-severe central sleep apnea. Treatment included oxygen therapy, SLP, physical therapy, albuterol, and cough assists. After discharge, the patient was frequently re-admitted with chronic respiratory failure and bronchiolitis and later had gastrostomy and tracheostomy tubes inserted. This specific case highlights the importance of implementing a diagnostic algorithm for neonatal hypotonia. It is also important for physicians, especially emergency medicine (EM) providers, to first exclude infection, sepsis, and cardiac and respiratory organ failure before looking into other tests. Then, physicians should evaluate for more rare etiologies. In this patient’s case, the hypotonia was due to a rare genetic disease, nemaline myopathy, and a multidisciplinary approach was used for this patient’s care.

show abstract

“…In the pediatric population of neuromuscular patients, the diagnostic yield was higher when genetic testing was matched with muscle biopsy findings (52). Congenital myopathies in particular show the highest degree of agreement between muscle biopsies findings and genetic results (53).…”

Section: Case Presentationmentioning

confidence: 99%

Case report: A novel ACTA1 variant in a patient with nemaline rods and increased glycogen deposition

Piga,

Rimoldi,

Magri

et al. 2024

Front. Neurol.

View full text Add to dashboard Cite

BackgroundCongenital myopathies are a group of heterogeneous inherited disorders, mainly characterized by early-onset hypotonia and muscle weakness. The spectrum of clinical phenotype can be highly variable, going from very mild to severe presentations. The course also varies broadly resulting in a fatal outcome in the most severe cases but can either be benign or lead to an amelioration even in severe presentations. Muscle biopsy analysis is crucial for the identification of pathognomonic morphological features, such as core areas, nemaline bodies or rods, nuclear centralizations and congenital type 1 fibers disproportion. However, multiple abnormalities in the same muscle can be observed, making more complex the myopathological scenario.Case presentationHere, we describe an Italian newborn presenting with severe hypotonia, respiratory insufficiency, inability to suck and swallow, requiring mechanical ventilation and gastrostomy feeding. Muscle biopsy analyzed by light microscopy showed the presence of vacuoles filled with glycogen, suggesting a metabolic myopathy, but also fuchsinophilic inclusions. Ultrastructural studies confirmed the presence of normally structured glycogen, and the presence of minirods, directing the diagnostic hypothesis toward a nemaline myopathy. An expanded Next Generation Sequencing analysis targeting congenital myopathies genes revealed the presence of a novel heterozygous c.965 T > A p. (Leu322Gln) variant in the ACTA1 gene, which encodes the skeletal muscle alpha-actin.ConclusionOur case expands the repertoire of molecular and pathological features observed in actinopathies. We highlight the value of ultrastructural examination to investigate the abnormalities detected at the histological level. We also emphasized the use of expanded gene panels in the molecular analysis of neuromuscular patients, especially for those ones presenting multiple bioptic alterations.

show abstract

The Role of Muscle Biopsy in Diagnostic Process of Infant Hypotonia: From Clinical Classification to the Genetic Outcome

Cited by 8 publications

References 17 publications

Clinical Characteristics and Neurologic Outcomes of X-Linked Myotubular Myopathy

Clinical Characteristics and Neurologic Outcomes of X-Linked Myotubular Myopathy

Nemaline Myopathy in a Hypotonic Neonate: Diagnostic Approach for Early Detection and Management

Case report: A novel ACTA1 variant in a patient with nemaline rods and increased glycogen deposition

Contact Info

Product

Resources

About