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Hypotonia of the newborn or infant is defined as decreased resistance to passive movement and is a frequent diagnostic challenge in pediatric practice. The hypotonic syndrome is a working diagnosis and its etiology must be identified to determine associated morbidities, prognosis, and management. Rapid advances in bioinformatics and molecular genetic testing allow for early accurate diagnoses in the diagnostic process. Therefore, it is necessary to carry out an updated review on this topic. The objective of this non-systematic narrative review is to describe the diagnostic approach to hypotonic syndrome and its main etiologies. A review of the literature from PubMed and Scielo databases was carried out, including relevant articles in English and Spanish published in the last 15 years. We emphasize the value of the clinical examination and history in locating the cause of hypotonia (cen tral or peripheral) as the first step toward the etiological diagnosis. Systemic diseases such as sepsis, hypoxic-ischemic encephalopathy, heart failure, and metabolic and electrolyte abnormalities are still common causes of central hypotonia. Peripheral hypotonia involves disorders of the anterior horn of the spinal cord, peripheral nerve, neuromuscular junction and muscle, of inherited and acquired origin. The use of images of the central nervous system and muscle and genetic panels and exome, constitute the most recent contributions to the diagnosis of hypotonic syndrome. This article propo ses an initial approach based on the main clinical clues leading to a certain diagnosis. Its therapy is supportive, except for some conditions that require specific treatment.

Non-dystrophic myotonias are a group of rare neuromuscular diseases linked to SCN4A or CLCN1. Among the subtypes, myotonia permanens, associated with the Gly1306Glu variant of SCN4A, is a relatively less frequent but more severe form. Most reports of non-dystrophic myotonias describe European populations. Therefore, to expand the genetic and phenotypic spectrum of this disorder, we evaluated 30 Chilean patients with non-dystrophic myotonias for associated variants and clinical characteristics. SCN4A variants were observed in 28 (93%) of patients, including 25 (83%) with myotonia permanens due to the Gly1306Glu variant. Myotonia permanens was inherited in 24 (96%) patients; the mean age of onset was 6 months, and the initial symptoms were orbicularis oculi myotonia in 17 (74%) patients and larynx myotonia in 12 (52%) patients. The extraocular muscles were involved in 11 (44%) patients, upper limbs in 20 (80%), and lower limbs in 21 (84%). Thirteen (52%) patients experienced recurrent pain and 10 (40%) patients reported limitations in daily life activities. Carbamazepine reduced myotonia in eight treated patients. The high frequency of the Gly1306Glu variant in SCN4A in Chilean patients suggests a founder effect and expands its phenotypic spectrum., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Sciatic neuropathy is rare and difficult to diagnose in pediatrics, and its long-term course has not been completely understood., Objective: To analyze the clinical presentation and evolution of a group of pediatric patients with sciatic neuropathy., Patients and Method: Retrospective anal ysis of the clinical characteristics of pediatric patients with sciatic neuropathy treated in two hospitals of Santiago between 2014 and 2018. Locomotor examination, muscle trophism, deep tendon reflexes, gait, sensation, and pain were assessed. Sciatic nerve conduction study and electromyography (EMG) were performed, and magnetic resonance imaging (MRI) in three patients., Results: Six patients were included with an average age of 11.8 years. The etiologies were traumatic (N = 2), by compression (N = 2), vascular (N = 1), and tumor (N = 1). All of the 6 patients presented foot drop and Achilles tendon hyporeflexia/areflexia, and 5 patients presented severe neuropathic pain. The EMG showed involvement of the sciatic nerve rami and dependent muscles. In two patients, a pelvic girdle and lower limbs MRI was performed, showing selective muscle involvement in sciatic territory. One patient underwent a lumbosacral plexus MRI, and subsequently histological study showing a benign neural tumor. Out of the three patients who were followed-up longer than one year presented motor sequelae and gait disorder., Conclusion: Sciatic neuropathy in the study group was secondary to different causes, predominantly traumatic and compressive etiologies. The three patients that were ina long-term follow-up presented significant motor sequelae. In most of the cases, neural injury wasassoci- ated with preventable causes, such as accidents and positioning in unconscious children, which is crucial in the prevention of a pathology with a high sequelae degree.

Introduction: Mucopolysaccharidoses (MPS) are rare and clinically heterogeneous lysosomal storage disorders. Carpal tunnel syndrome (CTS) is a frequent complication in MPS types I, II, VI, and VII. CTS symptoms are difficult to recognize in these children, and often there is a lack of appropriate investigations., Patients and Methods: In this retrospective study, all MPS patients were referred to the electrodiagnostic (EDX) laboratory of a single academic center during a 10-year period. Forty-eight children underwent serial EDX studies for CTS diagnosis and follow-up after surgery. Forty-two patients were diagnosed with CTS. Sensory nerve conduction velocity (SNCV), distal motor latency (DML), and motor nerve conduction velocity through the wrist (MNCV-W) of the median nerve were reviewed and analyzed., Results: One-hundred-three EDX examinations were performed on 48 patients. The median age at disease diagnosis was 2.1 years versus 4.9 years for CTS diagnosis. Analysis of the series revealed that electrophysiological abnormalities of CTS could have started much earlier (before the age of 2 years or at diagnosis of MPS). Diagnosis was based on SNCV and DML results, and MNCV-W was taken into consideration. Bilateral CTS was frequent (88%) in the types of MPS studied in our population and was observed from the first year of life, and may not have be associated with obvious clinical symptoms. EDX studies also helped in the follow-up and detection of CTS relapses, thus leading to an early intervention allowing a better recovery., Conclusion: EDX studies should be performed promptly and regularly in these patients. Prospective studies are required in order to understand the effect of disease-specific therapies in preventing the development of CTS in these patients., Synopsis: EDX studies should be performed in MPS patients soon after diagnosis and during routine follow-up, before and after surgical decompression.

Fibrodysplasia ossificans progressiva (FOP) or myositis ossificans, is a genetic disease, with a prevalence of 1 in 2.000.000. It is caused by pathogenic variants in ACVR1 gene and characterized by soft tissue heterotopic ossification, starting in the second decade of life. It is associated to early mortality caused by respiratory complications. It evolves in flare-ups, triggered by soft tissue injuries; therapy is symptomatic, using analgesia, steroids and diphosphonates. We report a 12-year-old female with left renal agenesis, hallux valgus and intellectual disability, presenting with a six months history of thoracic kyphosis, tender nodules in the thorax, and rigidity of right elbow and left knee. Clinical examination revealed dysmorphic facial features. A magnetic resonance showed heterotopic ossification nodules, which was confirmed with spinal radiography. These findings prompted the diagnosis of FOP. Pain treatment was started, and prednisone was used during flare-ups. The ACVR1 gene was analyzed and a pathogenic variant, p. Arg206His, was found, confirming the diagnosis of FOP.

Background: The myopathic form of carnitine palmitoyltransferase type II deficiency is an inherited autosomal recessive metabolic myopathy usually starting in childhood. Most reports have been on European and Japanese populations, and no Native South American patients have been reported to date. The p.Ser113Leu mutation is the most frequent in the European population. Only lower-leg magnetic resonance imaging findings have been reported, with gluteus maximus involvement in one case and normal imaging in other patients., Case Presentation: Two Native South American siblings, a boy and a girl, presented to our neuromuscular clinic with recurrent rhabdomyolysis associated with transient muscle weakness after prolonged exercise. During episodes, their creatine kinase concentrations were markedly increased, up to 148,000 (1.48 × 10 5 ) IU/L in the boy and 18,000 (1.8 × 10 4 ) IU/L in the girl. The results of electroneuromyography and histopathology suggested a nonspecific myopathy. CPT2 gene sequencing showed two heterozygous mutations: the p.Ser113Leu variant and a novel one (predicted to be deleterious by in silico analysis), the p.Ser373Pro variant. The patients' parents were asymptomatic carriers. Whole-body magnetic resonance imaging showed mild selective involvement in the thoracic extensors and pelvic girdle in both siblings, and in the thighs and lower legs in one of them. Dietary and bezafibrate treatment was started, and symptomatic relief was observed., Conclusions: To the best of our knowledge, this is the first reported Native South American family with a CPT2 deficiency carrying a novel mutation and particular features visualized by whole-body magnetic resonance imaging.

Introduction: The aim of this study was to delineate the spectrum of muscle involvement in patients with a myopathy due to mutations in SEPN1 (SEPN1-RM)., Methods: Whole-body magnetic resonance imaging (WBMRI) was used in 9 patients using T1-weighted turbo spin-echo (T1-TSE) sequences and short tau inversion recovery (STIR) in 5 patients., Results: Analysis of signal and volume abnormalities by T1-TSE sequences in 109 muscles showed a homogeneous pattern characterized by a recognizable combination of atrophy and signal abnormalities in selected muscles of the neck, trunk, pelvic girdle, and lower limbs. Severe wasting of sternocleidomastoid muscle and atrophy of semimembranosus were detected. Selective paraspinal, gluteus maximus, and thigh muscle involvement was also observed. The lower leg was less constantly affected., Conclusions: WBMRI scoring of altered signal and atrophy in muscle can be represented by heatmaps and is associated with a homogeneous, recognizable pattern in SEPN1-RM, distinct from other genetic muscle diseases., (© 2015 Wiley Periodicals, Inc.)

A paediatric and adult whole-body MRI (WB-MRI) protocol using a 1.5-T MRI system was used to examine 117 individuals (106 patients, 11 asymptomatic relatives). Genetic diagnosis was obtained in 38 subjects (RYR1, LMNA, COL6, DNM2, GAA, TPM2, SGCA, MYH7, NEB, SMN, FKBP14). T1-TSE WB-MRI sequences were abnormal in 67% of patients and 27% of asymptomatic relatives. Multiple striped signal abnormalities ('tiger-like') were very specific for COLVI-related myopathy. Distinct involvement of muscles in the head, neck, trunk, girdles and limbs was observed in patients with RYR1, SEPN1, GAA, LMNA or TPM2 mutations. Abnormalities and pattern recognition were more frequent in patients studied due to rigid spine syndrome (80% abnormal, recognisable in 75% of cases), hyperlaxity syndrome (75%; 50%) or with confirmed myopathy but absence of these markers (71%; 40%). Pattern was consistent with the molecular diagnosis in 97%. Mild clinical involvement was revealed by muscle testing in three parents with abnormal WB-MRI. The Garches WB-MRI protocol is suitable for a large spectrum of adults and children with early-onset neuromuscular disorders and can be used as an effective screening test in relatives. Recognition of characteristic patterns of abnormalities is improved by whole-body scanning compared with sequential MRI and, therefore, diagnostic impact is greater., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Mutations in the beta-tropomyosin gene (TPM2) are a rare cause of congenital myopathies with features of nemaline myopathy and cap disease and may also cause distal arthrogryposis syndromes without major muscle pathology. We describe the muscle biopsy findings in three patients with cap disease and novel heterozygous mutations in TPM2., Methods: Three unrelated patients with congenital myopathy were investigated by muscle biopsy and genetic analysis., Results: All three patients had early-onset muscle weakness of variable severity and distribution. Muscle biopsy demonstrated in all three patients near uniformity of type 1 fibers and an unusual irregular and coarse-meshed intermyofibrillar network. By electron microscopy, the myofibrils were broad and partly split, and the Z lines appeared jagged. In one of the patients caps structures were identified only by electron microscopy, and in one patient they were identified only in a second biopsy at adulthood. Three novel, de novo, heterozygous mutations in TPM2 were identified: a three-base pair deletion in-frame (p.Lys49del), a three-base pair duplication in-frame (p.Gly52dup), and a missense mutation (p.Asn202Lys)., Conclusions: Mutations in TPM2 seem to be a frequent cause of cap disease. Because cap structures may be sparse, other prominent features, such as a coarse-meshed intermyofibrillar network and jagged Z lines, may be clues to correct diagnosis and also indicate that the pathogenesis involves defective assembly of myofilaments.