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

The role of muscle biopsy in the diagnostic workup of floppy infants is controversial. Muscle sampling is invasive, and often, results are not specific. The rapid expansion of genetic approach has made the muscle histopathology analysis less crucial. This study aims to assess the role and efficacy of muscle histopathology in the diagnostic algorithm of hypotonia in early infancy through a retrospective analysis of 197 infants who underwent muscle biopsy in their first 18 months of life. Data analysis revealed that 92/197 (46.7%) of muscle biopsies were non-specific (80) or normal (12), not allowing a specific diagnosis. In 41/197 (20.8%) cases, biopsy suggested a metabolic or mitochondrial myopathy, while in 23/197 cases (11.7%), we found evidence of muscular dystrophy. In 19/197 cases (9.7%), histopathology characteristics of a congenital myopathy were reported. In 22/197 cases (11.7%), the histopathological study indicated presence of a neurogenic damage. Overall, 46 diagnoses were then achieved by oriented genetic tests. Muscle biopsy results were consistent with genetic results in 90% of cases. Diagnostic algorithms for the diagnosis of a floppy infant are largely missing. Muscle biopsy alone can lead to a diagnosis, help the clinician in the choice of a genetic test, or even modify a diagnosis made previously.

A floppy infant without lingual frenulum and kyphoscoliosis: Ehlers Danlos syndrome case report

Background Ehlers-Danlos syndrome (EDS) represents a group of connective tissue disorders characterized by the fragility of the soft connective tissues resulting in widespread skin, ligament, joint, blood vessel and internal organ involvement. The clinical spectrum is highly variable in terms of clinical features, complications, severity, biochemical characteristics and genes mutations. The kyphoscoliotic type EDS (EDS VIA) is a rare variant of the disease, with an incidence of 1:100.000 live births. EDS VIA presents at birth as severe muscular hypotonia, early onset of progressive kyphoscoliosis, marked hyperelasticity and fragility of the skin with abnormal scarring, severe joint hypermobility, luxations and osteopenia without a tendency to fractures. This condition is due to a mutation in the PLOD1 gene, and less commonly in FKBP14 gene, which results in the erroneous development of collagen molecules with consequent mechanical instability of the affected tissue. Case presentation A female newborn, found to be floppy at birth, presented a remarkable physical examination for joint hypermobility, muscle weakness, hyperelastic skin, a slight curve of the spine, the absence of the inferior labial and lingual frenulum. Due to severe hypotonia, neuromuscular disorders such as Spinal Muscular Atrophy (SMA), genetic diseases such as Prader Willi syndrome (PWS), myopathies and connective tissue disorders were considered in the differential diagnosis. Targeted gene sequencing were performed for SMN1, PLOD1, FKBP14, COL6A1, COL6A2, COL6A3. The urinary lysyl and hydroxy-lysyl pyridinoline ratio was diagnostic before discovering the homozygous duplication in the PLOD1 gene, which confirmed kyphoscoliotic EDS diagnosis. Conclusion In front of a floppy infant, a large variety of disorders should be considered, including some connective diseases. The presence at the birth of kyphoscoliosis, associated with joint hypermobility and the absence of the lingual and lower lip frenulum, should suggest an EDS.

MIOPATI KONGENITAL PADA BAYI: SEBUAH LAPORAN KASUS

Background: The congenital myopathies are group of genetic muscle disorders with a prevalence estimated between 1:22,480 in Sweden and 1:135,000 in Northern England. The most severe forms of congenital myopathy present In infant is the floppy infant with hypotonia and generalized musle weakness, and a frog leg posture, with facial, bulbar and respiratory weakness. We will provide an approach to the diagnosis of congenital myopathies with clinical examination, muscle imaging (MRI), muscle biopsy and identifying the genetic basis. Management of congenital myopathy are treatment of symptoms and complication caused by myopathies. Aim: To report a case of congenital myopathy in infant Case Description: A boy, a month, consulted from pediatric department to neurology department with chief complains the mouth is held in a open position, difficulty in feeding and generalized muscle weakness. From physical examintaion shows hypotonus in the masseter muscle, bulbar, respiration and all of extremities. In the chest cavity show pectus excavatum. Reflexes decrease in all of extremities with phatological reflexes in both lower extremities. We found pneumonia bilateral from thorax X-ray. ENMG shows moderate to severe axonal neuropathy and demyelination on all of extremities with normal EMG results. He received paracetamol 30 mg iv, ampicilin 150 mg iv, gentamicin 12 mg iv. He received exercise and chest fisiotherapy. After 22 days of treatment, he was discharge with clinical improvement. Conclusion: Patient has pneumonia bilateral caused by respiratory weakness congenital myopathy. Follow up and histological features is essential in guiding management for prediction of prognosis.