Clinical Reasoning: A 19-Month-Old Girl With Infantile-Onset Myopathy and White Matter Changes.

We describe the case of a 19-month-old girl presenting with gross motor delays, hypotonia, diminished deep tendon reflexes, hyperCKaemia, extensive white matter changes on MRI brain, and electromyography studies consistent with myopathy. The differential diagnosis for infantile-onset hypotonia and muscle weakness is broad. It includes numerous subtypes of genetic disorders, including congenital muscular dystrophies, congenital myopathies, congenital myasthenic syndromes, spinal muscular atrophy, single-gene genetic syndromes, and inborn errors of metabolism. We outline our clinical approach leading to the diagnosis of a distinctive genetic neuromuscular condition essential for neurologists and geneticists working with patients of all ages to recognize.

Two Turkish patients with Primary Coenzyme Q10 Deficiency-7: case report and literature review.

OBJECTIVES: Primary Coenzyme Q10 Deficiency-7 (OMIM 616276) results from bi-allelic pathogenic variants in the COQ4 gene. Common clinical findings include hypotonia, seizures, respiratory distress, and cardiomyopathy. In this report, we present two patients diagnosed with Primary Coenzyme Q10 Deficiency-7 along with a review of previously published cases, with the aim being to provide a better understanding of the clinical and laboratory manifestations of the disease. CASE PRESENTATION: A 3-month-and-22-day-old male was admitted to our outpatient clinic due to poor feeding and restlessness. He was born following an uneventful pregnancy to a nonconsanguineous marriage. A physical examination revealed hypotonia, a dolichocephaly, periorbital edema, and long eyelashes. Blood tests revealed metabolic acidosis and elevated serum lactate levels, while the genetic analysis revealed a variant previously reported as pathogenic, c.437T>G (p.Phe146Cys), in the COQ4 gene. Genetic tests were also conducted on both mother and father, and it revealed heterozygous variant, 0.437T>G (p.Phe146Cys), in the COQ4 gene. As a result of these findings, the patient was diagnosed with neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome (Primary Coenzyme Q10 Deficiency-7). A 1-year-old male was admitted to our clinic with complaints of hypotonia, seizures, and feeding difficulties. He was born following an uneventful pregnancy to a nonconsanguineous marriage. On his first day of life, he was admitted to the neonatal intensive care unit due to poor feeding and hypotonia. A physical examination revealed microcephaly, a high palate, poor feeding, weak crying, hypotonia, bilateral horizontal nystagmus, and inability to maintain eye contact. Laboratory findings were within normal limits, while a whole exome sequencing analysis revealed a homozygous variant previously reported as pathogenic, c.458C>T (p.A153V), in the COQ4 gene. The patient was diagnosed with Primary Coenzyme Q10 Deficiency-7. CONCLUSIONS: Primary Coenzyme Q10 Deficiency-7 should be considered in the differential diagnosis of infants presenting with neurological and dysmorphic manifestations.

[Degree of implementation in Spain of the therapeutic recommendations for hypotonia of central origin according to the consensus of experts of the American Academy for Cerebral Palsy and Developmental Medicine]. / Grado de implementación en España de las recomendaciones terapéuticas para la hipotonía de origen central según el consenso de expertos de la AACPDM.

INTRODUCTION: In early childhood, there are a number of different neurological conditions and syndromes that present with hypotonia of central origin. In 2019, the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) drew up a set of guidelines on therapeutic recommendations for the population aged from 0 to 6 years, based on the consensus of experts and on scientific evidence. The aim of this study is to determine how those therapeutic recommendations are being implemented in Spain. SUBJECTS AND METHODS: A survey of paediatric physiotherapists treating 0-6-year-old children with central hypotonia was carried out by means of a questionnaire consisting of 31 questions: 10 questions on sociodemographic and practice-related data, and the remaining 21 related to the use of the therapeutic recommendations based on the AACPDM guidelines for children with hypotonia of central origin. RESULTS: From a sample of 199 physiotherapists, it was found that familiarity with the AACPDM guidelines was significantly associated with the number of years of clinical experience, level of qualification and the community in which the professionals practise. CONCLUSION: These guidelines can serve to raise awareness and unify criteria regarding the therapeutic approach to children with central hypotonia. The results indicate that, with the exception of a few techniques, in our country most of the therapeutic strategies are being implemented within the framework of early care.

TITLE: Grado de implementación en España de las recomendaciones terapéuticas para la hipotonía de origen central según el consenso de expertos de la AACPDM.Introducción. En la primera infancia existen diferentes condiciones y síndromes neurológicos que presentan hipotonía de origen central. La American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) elaboró una guía en 2019 sobre recomendaciones terapéuticas para esta población de 0 a 6 años, basadas en un consenso de expertos y en la evidencia científica. El objetivo de este estudio fue ver cómo esas recomendaciones terapéuticas se están implementando en España. Sujetos y métodos. Se realizó una encuesta a fisioterapeutas pediátricos que tratan niños con hipotonía central de 0 a 6 años a través de un cuestionario que constaba de 31 preguntas: 10 preguntas sobre datos sociodemográficos y relativos al ejercicio de la profesión, y las 21 restantes relacionadas con el uso de las recomendaciones terapéuticas basadas en la guía de la AACPDM dirigidas a niños con hipotonía de origen central. Resultados. A partir de una muestra de 199 fisioterapeutas, se pudo objetivar que el conocimiento de la guía de la AACPDM se asociaba de forma significativa con los años de experiencia clínica, el nivel de titulación y la comunidad donde ejercen. Conclusión. Esta guía puede servir para concienciar y unificar los criterios en cuanto al abordaje terapéutico de los niños con hipotonía central. Los resultados indican que, excepto algunas técnicas, la mayoría de las estrategias terapéuticas se está implementado en nuestro país en el marco de la atención temprana.

Joubert syndrome: a case report of neonatal presentation and early diagnosis.

BACKGROUND: Joubert syndrome is a rare genetic condition with a prevalence of 1:80,000-1:100,000. In most cases, it shows an autosomal autosomal recessive hereditary pattern, although X-linked and autosomal dominant cases have been described. The distinctive characteristic of this syndrome is the malformation at cerebral and cerebellar levels, known as the "molar tooth sign," hypotonia, and delayed neurodevelopment. CASE REPORT: We describe the case of a newborn with transient tachypnea. However, during hospital stay, he showed other clinical signs not corresponding to the admission diagnosis, such as bradycardia, apneas, hypotonia, and alteration in swallowing mechanics. To rule out etiologies of central origin, we conducted a magnetic resonance of the brain and identified the "molar tooth sign," where the pathognomonic sign of Joubert syndrome. CONCLUSIONS: Rare genetic diseases may manifest as early as the neonatal period with non-specific signs. The early diagnosis of Joubert syndrome is reflected in better pediatric follow-up, which impacts its prognosis and the possibility of improving the patient's quality of life with a multidisciplinary management and genetic counseling.

INTRODUCCIÓN: El síndrome de Joubert es una rara condición genética con una prevalencia de 1:80,000 a 1:100,000. En la mayoría de los casos se presenta con un patrón de herencia autosómica recesiva, aunque se han reporatdo casos ligados al cromosoma X y autosómicos dominantes. La característica distintiva de este síndrome es la malformación a nivel cerebral y del cerebelo conocido como el "signo del molar", hipotonía y retraso en el neurodesarrollo. CASO CLÍNICO: Se describe el caso de un recién nacido con taquipnea transitoria del recién nacido; sin embargo, durante su estancia manifestó otros signos que no correspondían con el diagnóstico de ingreso, como bradicardia, apneas, hipotonía y alteración en la mecánica de la deglución. Para descartar etiologías de origen central, se realizó una resonancia magnética cerebral en la que se detectó el "signo del molar", patognomónico del síndrome de Joubert. CONCLUSIONES: Las enfermedades genéticas raras pueden manifestarse desde el periodo neonatal con signos muy inespecíficos. El diagnóstico precoz del Síndrome de Joubert permite un mejor seguimiento pediátrico que impacta en su pronóstico y en la posibilidad de mejorar la calidad de vida del paciente con un manejo multidisciplinario, así como brindar asesoramiento genético.

Extubation failure after cardiac surgery in children with Down syndrome.

Extubation failure (EF) after cardiac surgery is associated with poorer outcomes. Approximately 50% of children with Down syndrome (DS) have congenital heart disease. Our primary aim was to describe the frequency of EF and identify risk factors for its occurrence in a population of patients with DS after cardiac surgery. Secondary aims were to describe complications, length of hospital stay, and mortality rates. This report was a retrospective case-control study and was carried out in a national reference congenital heart disease repair center of Chile. This study includes all infants 0-12 months old with DS who were admitted to pediatric intensive care unit after cardiac surgery between January 2010 and November 2020. Patients with EF (cases) were matched 1:1 with children who did not fail their extubation (controls) using the following criteria: age at surgery, sex, and type of congenital heart disease. Overall, 27/226 (11.3%) failed their first extubation. In the first analysis, before matching of cases and controls was made, we found association between EF and younger age (3.8 months vs 5 months; p = 0.003) and presence of coarctation of the aorta (p = 0.005). In the case-control univariate analysis, we found association between an increased cardiothoracic ratio (CTR) (p = 0.03; OR 5 (95% CI 1.6-16.7) for a CTR > 0.59) and marked hypotonia (27% vs 0%; p = 0.01) with the risk of EF. No differences were found in ventilatory management. CONCLUSIONS: In pediatric patients with DS, EF after cardiac surgery is associated with younger age, presence of aortic coarctation, higher CTR reflecting the degree of cardiomegaly and hypotonia. Recognition of these factors may be helpful when planning extubation for these patients. WHAT IS KNOWN: • Extubation failure after cardiac surgery is associated with higher morbidity and mortality rates. Some studies report higher rates of extubation failure in patients with Down syndrome. WHAT IS NEW: • In children with Down syndrome, extubation failure after cardiac surgery is associated with younger age, presence of aortic coarctation, higher CTR reflecting cardiomegaly and severe hypotonia.

Serial Neurologic Examination in a Child With Acute Flaccid Weakness.

A 5-month-old healthy infant presented with acute flaccid weakness, anisocoria, and urinary retention with clinical suspicion of acute flaccid myelitis versus acute transverse myelitis.

Hypotonia: Is It a Clear Term and an Objective Diagnosis? An Exploratory Systematic Review.

BACKGROUND: Hypotonia is considered a determinant factor in multiple developmental disorders and is associated with various characteristics and morbidities. It is necessary to perform a systematic review to know which characteristics are described as associated with hypotonia in children and which methods are used for its diagnosis. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used to develop the systematic review protocol. A search of databases (Pubmed, Cochrane, Web of Knowledge, among others) was performed in May 2021 to identify relevant studies. Those describing characteristics or tests of hypotonia assessment were included, excluding those that exclusively addressed peripheral hypotonia. Two reviewers evaluated the articles and collected the data in a table, noting the authors, date of publication, type of study, and characteristics or tests described in relation to hypotonia. The quality of the studies was also assessed, and data were extracted. RESULTS: A total of 8778 studies were identified and analyzed, of which 45 met the inclusion criteria. Fifty-three characteristics associated with hypotonia and tests used for its evaluation were located, with pull to sit and vertical suspension being the most frequently referenced. CONCLUSIONS: The characteristics associated with hypotonia, more highly debated by authors are muscle strength, hypermobility, or the maintenance of antigravity postures. The most used test in the diagnosis of hypotonia is observation, followed by the pull-to-sit test, and adoption of frog posture. A unanimous understanding of the term hypotonia would favor further research.

El lactante hipotónico / The hypotonic infant

En la presente revisión pretendemos repasar conceptos básicos sobre la exploración y enfoque diagnóstico inicial del lactante hipotónico, centrándonos exclusivamente en aspectos recogidos mediante la anamnesis y la exploración, pilares fundamentales a la hora de abordar correctamente el diagnóstico de la hipotonía en el lactante. Mencionaremos las principales enfermedades que puedan manifestarse con hipotonía como síntoma guía, facilitando algunos datos clíni cos “clave” para la adecuada clasificación y enfoque diagnós tico. Subrayaremos la gran importancia en el momento actual de la identificación del lactante hipotónico arrefléxico, que exige de un despistaje urgente de la Atrofia Muscular Espinal (AME), que precisa de un tratamiento urgente (código AME En la presente revisión pretendemos repasar conceptos básicos sobre la exploración y enfoque diagnóstico inicial del lactante hipotónico, centrándonos exclusivamente en aspectos recogidos mediante la anamnesis y la exploración, pilares fundamentales a la hora de abordar correctamente el diagnóstico de la hipotonía en el lactante. Mencionaremos las principales enfermedades que puedan manifestarse con hipotonía como síntoma guía, facilitando algunos datos clíni cos “clave” para la adecuada clasificación y enfoque diagnós tico. Subrayaremos la gran importancia en el momento actual de la identificación del lactante hipotónico arrefléxico, que exige de un despistaje urgente de la Atrofia Muscular Espinal (AME), que precisa de un tratamiento urgente (código AME) (AU)

A 43-Day-Old Male With Respiratory Distress and Acute-Onset Hypotonia.

A 43-day-old, full-term, previously healthy male presented with decreased activity and oral intake. He was found to be grunting and hypoxemic on examination, and a respiratory pathogen panel was positive for rhinovirus. He was diagnosed with presumed bronchiolitis. His neurologic exam on admission was normal. Because of respiratory failure, he was escalated from high-flow nasal cannula to bilevel positive airway pressure upon admission and he was started on ceftriaxone and vancomycin while awaiting culture data. On hospital day 6, he required escalation of respiratory support. His examination at that time was notable for new hypotonia of his bilateral upper and lower extremities, sluggish pupils, bilateral exotropia, intermittent vertical nystagmus, and an absent Moro reflex. He developed a focal seizure and a computed tomography of the brain demonstrated simple right otomastoiditis. The seizure was attributed to a serum sodium of 113 mmol/L in the setting of syndrome of inappropriate antidiuretic hormone secretion, thought to be secondary to viral bronchiolitis. However, as the patient's sodium was corrected to a normal range, he continued to have neurologic deficits on examination. Given his persistent hypotonia and respiratory failure, atypical for the expected course of viral bronchiolitis, the patient underwent an extensive neurologic and infectious workup, which ultimately revealed a surprising diagnosis.

[Allan-Herndon-Dudley syndrome: a diagnosis to rule out in any male infant with undiagnosed hypotonia]. / Síndrome de Allan-Herndon-Dudley: un diagnóstico a descartar ante todo lactante varón con hipotonía sin causa determinada.

Allan-Herndon-Dudley syndrome is a rare X-linked genetic disorder, caused by a deficiency of the monocarboxylate transporter 8 (MCT8), a specific transporter of thyroid hormones, with functions mainly at the brain level. The syndrome produces an early onset of severe neurological disorder, in which hypotonia predominates. OBJECTIVE: To present a rare case with an unexpected diagnosis, highlighting the usefulness of requesting a complete thyroid profile in every hypotonic male infant without a specific cause. CLINICAL CASE: A 10-month-old male infant with severe axial and peripheral hypotonia, global weakness with little spontaneous mobility, without head support or stable sitting. Complete metabolic and peripheral neurophysiological studies were performed. Genetic studies for spinal muscular atrophy, Prader Willi syndrome, and myotonic dystrophy were also performed. The trio exome analysis detected a probably pathogenic variant c.359C>T;p.(Ser120Phe), hemizygous in exon 1 of the SLC16A2 gene, inherited from the mother. Thyroid abnormalities as increased free triiodothyronine (T3) and thyroid-stimulating hormone (TSH), and delayed myelination were ob served. CONCLUSIONS: MCT8 deficiency should be considered in the case of the male infant with unex plained hypotonia and weakness without a determined cause. The diagnosis is guided by a thyroid profile including free T3 hormone, because it presents a characteristic thyroid profile with decreased free thyroxine (T4), increased free T3, and normal or slightly elevated TSH levels. In this case, the implementation of the trio exome analysis allows establishing an early certain diagnosis.