Optic neuropathy diagnosis in the emergency room - retrospective observational study of the last 18 years.

INTRODUCTION: Optic neuropathies (ON), a broad spectrum of disorders of the optic nerve, are a frequent cause of visual loss, presenting either in isolation or associated to neurological or systemic disorders. They are often first evaluated in the Emergency Room (ER) and a rapid determination of the etiology is imperative for implementing timely and appropriate treatment. We aim to describe ER demographic data and clinical characteristics, as well as the performed imaging exams, of patients subsequently hospitalized and diagnosed with ON. Furthermore, we seek to explore the accuracy of ER discharge diagnosis and evaluate possible predictive factors that may influence it. METHODS: We retrospectively reviewed the medical records of 192 patients admitted to the ward of the Neurology Department of Centro Hospitalar Universitário São João (CHUSJ), with a discharge diagnosis of ON. Subsequently, we selected those admitted from the ER, with clinical, laboratory and imaging data, between January 2004 and December 2021. RESULTS: We included 171 patients. All participants were discharged from the ER and admitted in the ward with a main diagnostic suspicion of ON. Patients were stratified according to suspected etiology at the time of discharge: 99 inflammatory (57.9%), 38 ischemic (22.2%), 27 unspecified (15.8%) and 7 other (4.1%). By comparing with current follow-up diagnosis, 125 patients had an accurate ER diagnosis category (73.1%), 27 had an ON diagnosis of unspecified etiology that was defined only during follow-up (15.8%) and 19 had an inaccurate diagnosis category (11.1%). Diagnostic change was more common with ER ischemic diagnosis (21.1%) compared to inflammatory diagnosis (8.1%) (p = 0.034). CONCLUSIONS: Our study reveals that most patients with ON can be accurately diagnosed in the ER through clinical history neurological and ophthalmological evaluation.

Advancements in non-invasive imaging of atherosclerosis: Future perspectives.

Atherosclerosis is a chronic inflammatory disease characterized by the buildup of plaques in arterial walls, leading to cardiovascular diseases and high morbidity and mortality rates worldwide. Non-invasive imaging techniques play a crucial role in evaluating patients with suspected or established atherosclerosis. However, there is a growing body of evidence suggesting the need to visualize the underlying processes of plaque progression and rupture to enhance risk stratification. This review explores recent advancements in non-invasive assessment of atherosclerosis, focusing on computed tomography, magnetic resonance imaging, and nuclear imaging. These advancements provide valuable insights into the assessment and management of atherosclerosis, potentially leading to better risk stratification and improved patient outcomes.

Handwriting Changes in Alzheimer's Disease: A Systematic Review.

BACKGROUND: Handwriting is a complex process involving fine motor skills, kinesthetic components, and several cognitive domains, often impaired by Alzheimer's disease (AD). OBJECTIVE: Provide a systematic review of handwriting changes in AD, highlighting the effects on motor, visuospatial and linguistic features, and to identify new research topics. METHODS: A search was conducted on PubMed, Scopus, and Web of Science to identify studies on AD and handwriting. The review followed PRISMA norms and analyzed 91 articles after screening and final selection. RESULTS: Handwriting is impaired at all levels of the motor-cognitive hierarchy in AD, particularly in text, with higher preservation of signatures. Visuospatial and linguistic features were more affected. Established findings for motor features included higher variability in AD signatures, higher in-air/on-surface time ratio and longer duration in text, longer start time/reaction time, and lower fluency. There were conflicting findings for pressure and velocity in motor features, as well as size, legibility, and pen lifts in general features. For linguistic features, findings were contradictory for error patterns, as well as the association between agraphia and severity of cognitive deficits. CONCLUSIONS: Further re-evaluation studies are needed to clarify the divergent results on motor, general, and linguistic features. There is also a lack of research on the influence of AD on signatures and the effect of AD variants on handwriting. Such research would have an impact on clinical management (e.g., for early detection and patient follow-up using handwriting tasks), or forensic examination aimed at signatory identification.

A Giant Parathyroid Adenoma Presenting With Parathyroid Crisis.

Giant parathyroid adenomas (GPA) are a benign cause of primary hyperparathyroidism (PHPT) that might present similarly to parathyroid carcinomas (PC). Rarely, PHPT can present with a parathyroid crisis, a life-threatening decompensation with severe hypercalcemia.  A 77-year-old woman presented with lethargy and muscle weakness. Investigation revealed parathyroid hormone-dependent hypercalcemia and an enlarged parathyroid measuring 31x24 mm. The patient was submitted for parathyroidectomy. Histology showed no evidence of malignancy, confirming a GPA.  We report a GPA presenting with a parathyroid crisis. The clinical picture mimicked that of a PC. There are no clinical, analytical, or imagiological features pathognomonic of PC.

Comparison Between Clinical and Pathological Staging After Elective Neck Dissection in Head and Neck Cancer.

INTRODUCTION: Head and neck squamous cell carcinomas (HNSCC) are the most common malignancies in the head and neck. Previous studies have shown discrepancies in clinical and pathological staging, with a significant number of head and neck cancer patients who were not correctly staged. This has important implications regarding the treatment and prognosis of these patients. The aim of this study was to analyze potential disagreements in clinical and pathological staging in patients with head and neck cancer who underwent elective neck dissection. METHODS: A retrospective study of patients with squamous cell carcinoma of the head and neck, who underwent elective neck dissection, between January 2018 and December 2020. RESULTS: We analyzed 87 patients, with an average age of 64 ± 10.05 years, of whom 96.6% were male. The primary tumor location was the glottis (31%), oropharynx (26.4%), hypopharynx (19.5%), supraglottis (11.5%), and oral cavity (11.5%). In 87.3% there was a history of smoking and/or drinking. Pathological N (pN) staging was higher than clinical staging in 34.3% of patients (N1 in 22.9%; N2 in 8%; N3 in 3.4%). There were no significant differences between the number of nodes removed and the pN staging. However, there was a significant survival difference in patients with>15 nodes removed (p=0.05). There was also a significant difference in patients with pN up-staging regarding survival (p=0.005). Pathological T staging was different from clinical T staging (p<0.05), with an up-staging in 18.4% of the patients and a down-staging in 14.9%, without significant differences regarding survival or recurrence (p>0.05). Adjuvant treatment with radiotherapy was performed in 41.4% and with chemo-radiotherapy in 13.8% of the patients. Locoregional recurrence occurred in 17.5%. CONCLUSION: This study revealed that clinical and pathological N staging after elective neck dissection disagreed in a substantial number of patients, with pathological upstaging and significant differences regarding survival. With relation to T staging, there were no significant differences regarding survival. We should be aware of staging disagreements since they can have significant implications on the treatment and prognosis of cancer patients.

[Guidelines for the Diagnosis and Treatment of Spontaneous Intracranial Hypotension]. / Protocolo de Abordagem Diagnóstica e Terapêutica da Hipotensão Intracraniana Espontânea.

Spontaneous intracranial hypotension (SIH) is a syndrome characterized by disabling orthostatic headache, due to reduced cerebrospinal fluid (CSF) volume probably caused by a CSF fistula. It affects mostly women of working-age, although it is probably underdiagnosed. The aim of this article is to present a practical approach to the diagnosis and treatment of SIH. After a description of its symptoms and signs, we present a step-by-step approach to the confirmation of the diagnosis and treatment, considering different clinical scenarios. This is intended to guide clinical decision making, through a systematized and individualized management, aimed at the best interest of the patient.

A hipotensão intracraniana espontânea (HIE) é uma síndrome caracterizada por cefaleia ortostática incapacitante, fruto de uma redução do volume de líquido cefalorraquidiano (LCR) provavelmente causada por uma fístula de LCR. Afeta sobretudo mulheres em idade ativa, estando provavelmente subdiagnosticada. Este protocolo visa apresentar uma proposta de abordagem prática ao diagnóstico e tratamento da HIE. Após uma secção descritiva das manifestações clínicas da HIE, apresentamos um modelo de atuação passo-a-passo para a confirmação do seu diagnóstico e tratamento, considerando diferentes cenários clínicos. Pretende-se, assim, facilitar a decisão clínica através de uma conduta sistematizada e individualizada, visando o melhor interesse do doente.

Cognitive impairment in Neuromyelitis Optica Spectrum Disorder: A retrospective study using the Brief International cognitive Assessment for Multiple Sclerosis (BICAMS).

BACKGROUND: Neuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory disease of the central nervous system. The study aimed to characterize the neuropsychological profile of NMOSD by comparing them with multiple sclerosis (MS) patients and healthy controls. METHOD: Sixty-four participants were included:19 NMOSD, 27 MS, and 18 healthy controls. The neuropsychological protocol included the Portuguese version of Montreal Cognitive Assessment, the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), Verbal Fluency (phonemic and semantic), the Hospital Anxiety and Depression Scale, and the Expanded Disability Status Scale for clinical groups. RESULTS: NMOSD patients had significant lower cognitive performance when compared to HC mainly in information processing speed, concentration, language processing, and in executive functions (cognitive flexibility, sustained, and divided attention). No significant differences were observed between NMOSD and MS patients. Three predictors for cognitive impairment, according to BICAMS criteria, were found: depression, disease duration, and the level of disability. CONCLUSION: The neuropsychological profile found in the present study for NMOSD is consistent with the previous findings. Information regarding the predictors of cognitive impairment in both diseases and their different associations are important for future research and for guiding interventions more suitable for the neuropsychological needs of affected patients.

Expanding the genetic spectrum of ALKU syndrome: Compound heterozygosity for two deleterious variants in SMG8 gene.

Alzahrani-Kuwahara syndrome (ALKUS) is a neurodevelopmental disorder that includes microcephaly, facial dysmorphism, and variable congenital and eye malformations. We present the first case of ALKUS described in the European population caused by two variants in compound heterozygosity of the gene SMG8. We present a patient with two variants in compound heterozygosity in the SMG8 gene identified by in trio whole exome sequencing based in next generation sequencing (xGEN® Exome Research Panel, Nextseq550 platform). International case reporting (CARE) criteria were followed. Patient written consent was obtained through legal responsible persons. We describe a 27-year-old male, the second child of a healthy and non-consanguineous couple, whose genetic analysis showed two variants in compound heterozygosity, c.1159C > T (p.Arg387*) and c.2407del (p.Arg803Glyfs*10), in the SMG8 gene, both classified as likely pathogenic. As described by Fatema Alzahrani et al. in a series of eight patients, our patient had global developmental delay with impaired intellectual development, facial dysmorphism, and limb disproportion. Additionally, our patient had lower limb spastic paraparesis, marked osteotendinous hyperreflexia with extensor plantar response bilaterally and paretic gait. Our patient resembles the phenotype described by Fatema Alzahrani et al., however, he is the first patient with two SMG8 deleterious variants in compound heterozygosity, and the first to exhibit pyramidal signs and gait disorder as part of the phenotype.

Recurrent encephalopathy associated with pegylated beta-interferon treatment.

A 62-year-old woman with a history of multiple sclerosis (MS) presented with recurrent episodes of confusion, dysarthria and gait difficulties. These episodes occurred about 3 days after administration of pegylated interferon-beta-1a (Plegridy®) and resolved spontaneously in around 4 days. The brain MRI scan, laboratory findings and cerebrospinal fluid analysis during these episodes were negative for other causes of encephalopathy. She discontinued treatment with interferon and was started on teriflunomide, experiencing no recurrence of symptoms. We believe that interferon was responsible for this patient's recurrent encephalopathic syndrome, possibly due to its effects on inflammatory cytokines and endothelial dysfunction.

Genetic Diversity and Population Structure of Cowpea (Vigna unguiculata (L.) Walp.) Landraces from Portugal and Mozambique.

Cowpea (Vigna unguiculata (L.) Walp.) is currently a legume crop of minor importance in Europe but a highly relevant staple crop in Africa and the second most cultivated legume in Mozambique. In Portugal and Mozambique, cowpea's phenotypic and genetic variation has been maintained locally by farmers in some areas. We used the molecular markers SSR, SilicoDArT and SNP to analyze the genetic diversity and population structure of 97 cowpea accessions, mainly from Portugal (Southern Europe) and Mozambique (Southern Africa). As far as we know, this is the first time that the genetic variation and the relationship between cowpea landraces collected in Portugal with those originated in Mozambique is reported. Despite the shared historical past, the Portuguese landraces did not share a common genetic background with those from Mozambique, and two different gene pools were revealed. Knowledge of the genetic structure of cowpea landraces offers an opportunity for individual selection within landraces adapted to particular eco-physiological conditions and suggests the existence of a valuable gene pool for exploitation in future Portugal-PALOP (Portuguese-speaking African countries) cowpea breeding programs.

Development and validation of the clinical report form for nodular thyroid pathologies

Abstract Objectives: The aim of this study is to develop and validate a novel clinical report form in the format of a structured interview to enable the characterization of the Portuguese population of the Baixo Vouga region with different subtypes of nodular thyroid pathologies (NTyPs). Materials and methods: A structured interview was developed and to the best of our knowledge, this is the first structured interview built and validated for that purpose in Portugal. Results: This structured interview enables the identification of possible correlations between each subtype of nodular lesions and sociodemographic data, consumption habits and lifestyle, endocrine history, and family predisposition. Conclusion: The novel structured interview will simultaneously, enable a detailed characterization of the group of patients with nodular thyroid lesions and will support future metabolomic studies.

Natural history of familial cerebral cavernous malformation syndrome in children: a multicenter cohort study.

PURPOSE: There is limited data concerning neuroimaging findings and longitudinal evaluation of familial cerebral cavernous malformations (FCCM) in children. Our aim was to study the natural history of pediatric FCCM, with an emphasis on symptomatic hemorrhagic events and associated clinical and imaging risk factors. METHODS: We retrospectively reviewed all children diagnosed with FCCM in four tertiary pediatric hospitals between January 2010 and March 2022. Subjects with first available brain MRI and [Formula: see text] 3 months of clinical follow-up were included. Neuroimaging studies were reviewed, and clinical data collected. Annual symptomatic hemorrhage risk rates and cumulative risks were calculated using survival analysis and predictors of symptomatic hemorrhagic identified using regression analysis. RESULTS: Forty-one children (53.7% males) were included, of whom 15 (36.3%) presenting with symptomatic hemorrhage. Seven symptomatic hemorrhages occurred during 140.5 person-years of follow-up, yielding a 5-year annual hemorrhage rate of 5.0% per person-year. The 1-, 2-, and 5-year cumulative risks of symptomatic hemorrhage were 7.3%, 14.6%, and 17.1%, respectively. The latter was higher in children with prior symptomatic hemorrhage (33.3%), CCM2 genotype (33.3%), and positive family history (20.7%). Number of brainstem (adjusted hazard ratio [HR] = 1.37, P = 0.005) and posterior fossa (adjusted HR = 1.64, P = 0.004) CCM at first brain MRI were significant independent predictors of prospective symptomatic hemorrhage. CONCLUSION: The 5-year annual and cumulative symptomatic hemorrhagic risk in our pediatric FCCM cohort equals the overall risk described in children and adults with all types of CCM. Imaging features at first brain MRI may help to predict potential symptomatic hemorrhage at 5-year follow-up.

Metabolic syndrome parameters and multiple sclerosis disease outcomes: A Portuguese cross-sectional study.

BACKGROUND: Metabolic syndrome and multiple sclerosis [MS] share the presence of chronic inflammation in their pathogenic mechanisms. This study aimed to estimate the prevalence of metabolic syndrome parameters in MS and their association with disease disability, cognitive function, and Neurofilament Light chain [NfL] levels. METHODS: Clinical, analytical, and magnetic resonance imaging data were obtained through medical records. Disease disability was measured by the Expanded Disability Status Scale [EDSS], the MS Severity Scale [MSSS] along with cognitive impairment by the Brief International Cognitive Assessment for MS [BICAMS] and Word List Generation test [WLG]. Metabolic syndrome parameters were evaluated by fasting blood glucose, triglycerides, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol, total cholesterol, blood pressure, and waist circumference [WC]. We also analysed serum leptin and ghrelin and cerebrospinal fluid NfL. RESULTS: Our sample included 51 people with MS, 34 (66.7%) females, mean age of 38.20±12.12 years and median disease duration of 3 years (P25=2.0, P75=5.0). Multivariate linear regression analysis confirmed that WC correlates with EDSS (ß=0.04, p=.001) and MSSS (ß=0.07, p=.002) as well as Brief Visuospatial Memory Test-Revised (ß=-0.29, p=.008), WLG (ß=-0.20, p=.039). NfL is also negatively associated with HDL-C (ß=-4.51, p=.038). CONCLUSIONS: Waist circumference is associated with disability and deficits in cognitive tests. A decrease in HDL-C is associated with an increase in NfL. This suggests metabolic syndrome might be an important factor in MS disease course.

Dysfunction of norepinephrine and its metabolites in Alzheimer's dementia - A review with meta-analysis.

Some studies point locus coeruleus cell loss, the central nervous system main source of norepinephrine, to be one of the earliest neuropathological events of Alzheimer's disease (AD). However, there are conflicting reports regarding the level of norepinephrine and its metabolites (3-Methoxy-4-hydroxyphenylglycol (MHPG), 3,5-dihydroxyphenylglycine (DHPG) and 3,4 -dihydroxyphenylglycolaldehyde (DOPEGAL)) in AD patients. Uncover these alterations may be a key factor for understanding cognitive deficits and AD pathology. We review the literature that compare norepinephrine and its metabolites between AD patients and non-demented controls. A meta-analysis did not reveal significant statistical differences, but there was a trend towards a lower level of norepinephrine of AD, with almost no difference in MHPG in the cerebrospinal fluid. Regarding MHPG in plasma, DHPG and DOPEGAL we only performed a qualitative analyse due to the small or absent number of studies. These findings point to a decrease in norepinephrine, what is in line with locus coeluleus cell loss in AD. The absence of statistical difference and an equal level of MHGP could indicate a compensatory mechanism.

Development and validation of the clinical report form for nodular thyroid pathologies.

Objective: The aim of this study is to develop and validate a novel clinical report form in the format of a structured interview to enable the characterization of the Portuguese population of the Baixo Vouga region with different subtypes of nodular thyroid pathologies (NTyPs). Materials and methods: A structured interview was developed and to the best of our knowledge, this is the first structured interview built and validated for that purpose in Portugal. Results: This structured interview enables the identification of possible correlations between each subtype of nodular lesions and sociodemographic data, consumption habits and lifestyle, endocrine history, and family predisposition. Conclusion: The novel structured interview will simultaneously, enable a detailed characterization of the group of patients with nodular thyroid lesions and will support future metabolomic studies.

Gestational Diabetes: Which Clinical (Pre)gestational Features Are Able to Predict Failure of Lifestyle Intervention?

Background Controversy exists regarding risk factors in pregnant women that might be associated with a higher probability of failure of lifestyle intervention in the treatment of gestational diabetes (GD). These pregnant women's risk factors may highlight the need for closer surveillance at an early stage of pregnancy. Aims To identify predictors of pharmacological therapy need in early and late GD. Methods This was a retrospective observational study including women with GD diagnosed in the first (group 1) or second trimester (group 2) according to the criteria proposed by the International Association of Diabetes Pregnancy Study Group (IADPSG), singleton pregnancy and follow-up between January 2015 and December 2018, divided according to treatment (lifestyle intervention or pharmacological treatment (metformin and/or insulin)). Results A total of 278 and 273 women were included in groups 1 and 2, of which 48.6% and 55.3% underwent non-pharmacological treatment, respectively. In group 1, women requiring pharmacological therapy tended to be older and have previous GD or family history of diabetes, higher body mass index (BMI) and higher fasting blood glucose (FBG) levels. In group 2, pharmacological treatment need was associated with multiparity, previous GD, higher BMI, higher fasting glucose value in the oral glucose tolerance test (OGTT), and higher OGTT value at 60 minutes. The independent risk factors identified for pharmacological treatment requirement were maternal age (OR 1.10 (1.05-1.16), p<0.001), previous GD (OR 2.70 (1.10-6.58), p=0.029) and FBG (OR 1.07 (1.00-1.14), p=0.048) in group 1 while BMI (OR 1.07 (1.02-1.13), p=0.012) and fasting glucose value in the OGTT (OR 1.03 (1.01-1.05), p=0.006) were the factors identified in group 2. The cut-off values for FBG and fasting glucose value in the OGTT that predicted the necessity of pharmacological treatment were 95.50 mg/dL and 88.50 mg/dL, respectively. Conclusions In early GD, closer surveillance is necessary for older women with a previous GD and an FBG ≥ 95.50 mg/dL. In late GD, pre-gestational BMI and a fasting glucose value in the OGTT ≥ 88.50 mg/dL should prevail.

Subclinical Hypothyroidism in Pediatric Age: How Important Is Autoimmunity?

Background The natural history of subclinical hypothyroidism (SHT) is influenced by the underlying etiology, being the most common Hashimoto's thyroiditis (HT) and isolated hyperthyrotropinemia (IH). Additionally, controversy exists surrounding the need for pharmacological treatment. Methods A retrospective observational study that included patients diagnosed with SHT caused by HT or IH at pediatric age, under levothyroxine therapy and with follow-up at Centro Hospitalar Baixo Vouga between January/2014 and July/2019. Patients with follow-up time <12 months or missing records were excluded. This study aims to compare clinical, analytical and echographic parameters and levothyroxine dose between patients with SHT caused by HT or IH. Results Sample of 39 patients with 16.5 ± 3.4 years, 22 (56.4%) females. There was a preponderance of females in the HT group and males in the IH (p=0.001). Changes in thyroid ultrasound were more prevalent in the HT group (85.7% vs 16.7%, p<0.001). The median initial and final doses of levothyroxine were higher in the HT group (p=0.016, p=0.011). There was a trend towards a higher levothyroxine discontinuation rate in the IH group (22.2% vs 4.8%, p=0.162). Two positive and statistically significant correlations were found between the level of anti-thyroid peroxidase antibodies (TPOAbs) and both the final levothyroxine dose (ρ=0.544; p=0.004) and the final weight-adjusted levothyroxine dose (ρ=0.434; p=0.027). Conclusions HT was more common in females and was associated with higher levothyroxine requirements and less likelihood of treatment discontinuation, especially if high TPOAbs levels. These results can be useful in the difficult daily decision of starting therapy, especially in milder forms of SHT.

Common variable immunodeficiency and its inflammatory neurological manifestations: A case report and literature review.

BACKGROUND: Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies characterized by impaired immunoglobulin production and dysregulated immune response. Neurological manifestations have been described in a few patients, and little is known about its clinic and therapeutic approach. Thus, this work aimed to review the literature on it and to help differentiate CVID from its mimics, especially sarcoidosis. METHODS: We described a case report and included a literature review of inflammatory neurological involvement in CVID. RESULTS: A 32-year-old female patient with a medical history of recurrent bacterial infections, temporal focal epilepsy and granulomatous lung disease under study, and cervix squamous cell carcinoma, was initially admitted to the emergency department due to intracranial hypertension. After excluding infectious and neoplastic etiologies, the most likely hypothesis was that granulomatous pulmonary, cerebral, and leptomeningeal inflammatory involvement were associated with sarcoidosis. Two years later, a diagnosis of CVID was made, and the patient was secondarily diagnosed with Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD) and related inflammatory brain disease - both complications of CVID. After starting targeted treatment with immunoglobulin replacement and pulse glucocorticoids followed by a chronic taper, the patient became stable. However, three consecutive failures in immunoglobulin intake during the COVID-19 pandemic led to disease recurrence with relapse of neurological manifestations. CONCLUSION: This case illustrates the complex multiple organ manifestations of CVID. When granulomatous conditions arise in these patients, a rare lung disease arising in the context of CVID, the GLILD disease with multisystem involvement, should be taken into consideration. Early treatment with combined steroids and immunotherapy seems to be effective in controlling CVID's neurological manifestations.

Congenital myopathies in adults: A diagnosis not to overlook.

BACKGROUND: Congenital myopathies (CM) were traditionally classified according to the muscle histopathological features, but in recent years, molecular diagnosis has become increasingly important. CM may present a wide phenotype variability, and while adult-onset CM have been increasingly recognized, substantial diagnostic delays are still reported. OBJECTIVES: To describe a cohort of adult CM patients, including clinical, genetic, and histopathological features, and further characterize the subgroup of adult-diagnosed patients. MATERIALS AND METHODS: We performed a retrospective observational cohort study to characterize the CM patients evaluated in our adult Neuromuscular outpatient clinic, including the subgroup of adult-diagnosed patients. RESULTS: We identified 19 CM patients with compatible molecular and/or histological diagnoses, of which 14 were diagnosed in adulthood. Eleven adult-diagnosed patients had symptoms since childhood and 9 had a family history of myopathy. The median age of symptoms' onset was 4 years old and the median age at diagnosis was 37 years old. The most common causative gene was RYR1, followed by TTN and MYH7. Three patients had non-specific features on muscle biopsy, all diagnosed during adulthood. CONCLUSIONS: In our cohort, the majority of CM were diagnosed in adulthood, despite most having pediatric-onset symptoms and positive family history. The diagnostic delay may be associated with mild presentation, slow course, atypical muscle histology, and lack of awareness of adult-onset CM. Studies with larger populations are needed.