The genetic profile of childhood neuromuscular disorders: A single center experience

Neuromuscular Diseases are a heterogeneous group of childhood disorders, and differential diagnosis can be challenging. Although there is no definitive treatment for the most of this group of diseases, early diagnosis is important with the development of new treatment methods. In this study, we aimed to draw attention to the importance of new generation genetic tests in diagnosing neuromuscular diseases. In this retrospective study, we reviewed the records of 800 patients with suspected neuromuscular diseases followed in the Neuromuscular Clinic of Marmara University Pendik Training and Research Hospital between December 2011 and January 2023 according to their demographic, clinical and genetic characteristics. Patients who were diagnosed with Duchenne muscular dystrophy and spinal muscular atrophy with targeted gene testing were excluded from the study. The results of targeted gene testing, clinical exome sequencing (CES), whole exome sequencing (WES) and mitochondrial genome analysis were analysed

Genomic variants causing mitochondrial dysfunction are common in hereditary lower motor neuron disease

Hereditary lower motor neuron diseases (LMND) other than 5q-spinal muscular atrophy (5q-SMA) can be classified according to affected muscle groups. Proximal and distal forms of non-5q-SMA represent a clinically and genetically heterogeneous spectrum characterized by significant overlaps with axonal forms of Charcot-Marie-Tooth (CMT) disease. A consensus for the best approach to molecular diagnosis needs to be reached, especially in light of continuous novel gene discovery and falling costs of next-generation sequencing (NGS). We performed exome sequencing (ES) in 41 families presenting with non-5q-SMA or axonal CMT, 25 of which had undergone a previous negative neuromuscular disease (NMD) gene panel analysis. The total diagnostic yield of ES was 41%. Diagnostic success in the cohort with a previous NMD-panel analysis was significantly extended by ES, primarily due to novel gene associated-phenotypes and uncharacteristic phenotypic presentations. We recommend early ES for individuals with hereditary LMND presenting uncharacteristic or significantly overlapping features. As mitochondrial dysfunction was the underlying pathomechanism in 47% of the solved individuals, we highlight the sensitivity of the anterior horn cell and peripheral nerve to mitochondrial imbalance as well as the necessity to screen for mitochondrial disorders in individuals presenting predominant lower motor neuron symptoms

The frequency of late-onset Pompe disease in pediatric patients with limb-girdle muscle weakness and nonspecific hyperCKemia: A multicenter study

The aim of this multicenter study was to screen for late-onset Pompe disease in high-risk children with limb-girdle muscle weakness and nonspecific hyperCKemia using the dried blood spot (DBS) test. Seventy-two children from four pediatric neurology departments in Turkey were enrolled in the study: 37 with limb-girdle muscle weakness and 35 with nonspecific hyperCKemia. Acid alpha-glucosidase (GAA) activity Was measured on DBS by tandem mass spectrometry. Six patients tested positively for Pompe disease. In three patients, one with the limb-girdle muscle weakness and two with nonspecific hyperCKemia, this was confirmed by genetic analysis. The overall frequency of late-onset Pompe disease in the study population was 4.2%. The c.1784C>T mutation found in one patient is a new mutation whereas the c.1655T>C mutation detected in the other two patients is not novel. In conclusion, Pompe disease should be suspected in patients with limb-girdle muscle weakness and nonspecific hyperCKemia. The DBS test is a safe and reliable method of diagnosis but must be confirmed by genetic analysis. In patients with a positive DBS test and negative genetic analysis, tissue assay of GAA should be considered. (C) 2016 Published by Elsevier B.V

Phacomatosis pigmentokeratotica associated with unilateral toe walking due to short achilles tendon

Phacomatosis pigmentokeratotica (PPK) is characterized by the co-occurrence of speckled lentiginous nevus (nevus spilus) and an organoid nevus with or without extracutaneous involvement. The extracutaneous manifestations may vary widely with musculoskeletal, neurologic, ocular, and vascular findings. The PPK is also associated with an increased risk of cutaneous or extracutaneous tumors. Therefore, the patients with PPK should be followed up regularly for possible malignant transformation. Here, we report a 5-year-old boy with PPK associated with toe walking due to short Achilles tendon, which was not previously reported, to our knowledge

Stakeholder Engagement and Perceptions on Water Governance and Water Management in Azerbaijan

To undertake the modernization of Azerbaijan’s water sector, the government of Azerbaijan collaborated with the Food and Agriculture Organization (FAO) of the United Nations (UN) in a comprehensive initiative to explore stakeholder perceptions on in-country water governance. The research approach, designed by national water experts and the authors, resulted in the development and administration of a stakeholder engagement and perception survey. The survey, implemented in 2022, elicited responses from a total of 219 state and non-state actors. To enrich interpretations of the survey, this study furthers the analysis of the government commissioned FAO stakeholder survey results and sheds additional insights as to where stakeholders see problems in water governance processes. This independent study informs the broader FAO project and generates supplemental recommendations to the Azerbaijani government for legislative and executive-level action to make Azerbaijan’s water sector more resilient as the climate changes and water insecurity increases. Even though an impressive number of 219 stakeholders participated in the survey, 80% of the responses were from state stakeholders, thus introducing significant bias into the dataset. In order to cope with the bias and make the best of the dataset, the authors analyzed the responses with a customized categorical methodology. Stakeholders were categorized into state, non-state, decision-maker, or executive groups and were examined for trends using various Pareto analyses. Interpretation of the survey responses reveals that, while stakeholders in the water sector interact through informal and formal means, stakeholder groups, to a large extent, lack an understanding of the barriers to stakeholder engagement in water-related policy matters. The stakeholders that indicate understanding of challenges accompanying water policy engagement note a lack of data, a lack of human and institutional capacity, and a lack of financial support to be some of the most common obstacles encountered in the sector. Furthermore, perceptions differ regarding the need for governance reform, the criticality of climate change, institutional resistance to change, policy or practice gaps, transparency, and variables needed for successful stakeholder engagement across all sectors. Such variations in perceptions illustrate the need for restructuring stakeholder interactive platforms and financial channeling to lead to better water governance and water management

Gomez-Lopez-Hernandez Syndrome: A Rare Cause of Bilateral Nonscarring Alopecia

Gomez-Lopez-Hernandez syndrome is a rare neurocutaneous disorder characterized by the triad of rhombencephalosynapsis, parietal alopecia, and trigeminal anesthesia. We report a 16-year-old girl with bilateral parietotemporal alopecia in whom cranial magnetic resonance imaging revealed rhombencephalosynapsis, suggesting a diagnosis of Gomez-Lopez-Hernandez syndrome. Neurologic examination and neuroimaging may be warranted in select patients with parietal alopecia to exclude this uncommon entity

Water Pricing in Turkey with special reference to the Southeastern Anatolia Project (GAP)

Cet article examine le système d'évaluation du prix de l'eau actuel en Turquie en se référant tout particulièrement au projet du sud-est d'Anatolia où un système d'irrigation conçu pour couvrir 1,7 millions d'ha de terre est en cours de développement. À la lumière du projet pilote avec une participation de l'irrigation à la gestion, il énumère également les mesures possibles qui sont exigées et à prendre pour réaliser une politique des prix raisonnable et pratique de l'eau

The association between febrile seizures and iron deficiency anemia in childhood

Amaç: Çocukluk çağında en sık görülen konvülziyon tipi olan febril konvülziyonun etiyolojisi ve risk faktörleri içinde son yıllarda demir eksikliği anemisi üzerinde durulmaktadır. Çalışmamızda demir eksikliği ve demir eksikliği anemisiyle febril konvülziyon arasındaki ilişkinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Kasım 2003- Ağustos 2004 tarihleri arasında hastanemiz Çocuk Hastalıkları polikliniği ve acil servise başvuran yaşları 6 ay ile 5 yaş arasında 139 çocuk çalışmaya dahil edildi. Hastalarda demir eksikliği anemisi ve febril konvülziyon tanıları Amerikan Pediatri Akademisi kriterlerine göre belirlendi. Çalışma grubu, bir veya birden fazla febril konvülziyon geçirmiş, antiepileptik tedavi almayan 93 çocuktan oluştu. Kontrol grubu ateşli hastalığı olan konvülziyon geçirmemiş (n=21) ve sağlıklı çocuklardan (n=25) oluşturuldu. Bulgular: Çalışma grubu ve kontrol grupları arasında Hb, MCV ve ferritin düzeylerinde istatistiksel olarak anlamlı bir fark saptanmadı (p>0,05). Febril konvülziyon grubunda sağlıklı çocuk ve ateşli kontrol grubuna göre serum demir düzeyi anlamlı düşük bulundu. Tartışma: Çalışmamızda febril konvülziyonlu çocuklarda demir eksikliği anemisi oluşmadan serum demir düzeyinde düşüklük saptanması, febril konvülziyonda demir eksikliğinin kolaylaştırıcı belki de tetikleyici faktör olabileceğini düşündürmektedir. Ancak bu bulguyu aydınlatmak için daha fazla standardize edilmiş kontrollü çalışmaya ihtiyaç vardır.Aim: Febrile seizures are the most common seizure type in childhood. In recent years febrile seizures are linked with iron deficiency anemia. The aim of this study is to evaluate the association between febrile seizures and iron deficiency and iron deficiency anemia. Material and Method: 139 children, aged 6 months to 5 years, admitted to our pediatric outpatient and emergency clinic between November 2003 and August 2004 were enrolled in the study. The diagnosis of iron deficiency anemia and febrile seizures were made according to the criteria of American Academy of Pediatrics. The study group consisted of 93 children with one or more febrile convulsions. None of them was on antiepileptic therapy. The control groups consisted of children with a febrile illness in the absence of convulsions (n=21) and healthy children (n=25). Results: There was no statistically significant difference in Hb, MCV and ferritin levels between the study and control groups (p>0,05). The serum iron levels were lower in the children with febrile seizures compared to the children with a febrile illness in the absence of febrile seizures and healthy children. The result is statistically significant (p<0,05). Discussion: The present study showed that the percentage of iron deficiency is higher in the children with febrile seizures compared to the control groups even before the anemia develops. The results of this study suggest that iron deficiency may play a role in the etiopathogenesis of febrile seizures. However, further standardized and controlled studies are required to evaluate this finding

How do presentation age and CSF opening pressure level affect long-term prognosis of pseudotumor cerebri syndrome in children? Experience of a single tertiary clinic

Background: Diagnosis and treatment of pseudotumor cerebri syndrome in children is still a challenge for clinicians. The aim of this study is to reveal the influence of presentation age and CSF opening pressure on long-term prognosis of pseudotumor cerebri and share our clinical data of the very young age (≤ 5-year) group. Method: This retrospective study includes the patients followed by the Marmara University Pediatric Neurology Clinic between years 2012 and 2020 diagnosed with definite, probable, or suggestive pseudotumor cerebri syndrome according to modified Friedman criteria. Patients were classified into three groups according to presentation age: group 1: ≤ 5 years old; group 2: 6–10 years; and group 3 > 10 years old. CSF opening pressure was also categorized into three groups as CSF 30 cmH20. Results: One hundred three patients, 62.1% female (n = 64), were enrolled in the study. Group 1 consisted of 16 patients (60% male), group 2 consisted of 30 patients (63.3% female), and group 3 consisted of 57 patients (66.7% female). The mean CSF opening pressure did not differ between the three age groups in our study (p > 0.05). Treatment response was not correlated with CSF opening pressure. Papilledema presence and level of CSF opening pressure were independent of age (p > 0.05). Conclusions: Age at presentation and CSF opening pressure at diagnosis are not any predictive factors that influence long-term prognosis of pseudotumor cerebri syndrome in children. Evaluation and follow-up of children should be done in personalized approach. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature