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1.
Further evidence of affected females with a heterozygous variant in FGF13 causing X-linked developmental and epileptic encephalopathy 90.
Narayanan, DL, Majethia, P, Shrikiran, A, Siddiqui, S, Dalal, A, Shukla, A
European journal of medical genetics. 2022;(1):104403
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Abstract
Developmental and epileptic encephalopathies (DEE) are a genetically heterogeneous group of disorders characterised by early onset epilepsy, epileptiform activity on electroencephalogram and associated developmental delay or neuroregression. With the advent of high throughput sequencing, novel gene-disease associations have been described for DEEs. Voltage activated sodium channels (Nav) regulate neuronal excitability. Fibroblast growth factor homologous factors (FHFs) are proteins, which bind to the C terminal cytoplasmic tails of alpha subunits of Nav channels and influence their function and surface expression. Gain of function hemizygous or heterozygous variants in FGF13 (also known as FHF2) were recently identified as the cause for X-linked developmental and epileptic encephalopathy 90 (DEE90; MIM# 301058) in seven individuals from five families, which included one female. We report an additional female, providing further evidence for a novel de novo heterozygous missense variant in FGF13, NM_004114.5: c.14T > G p.(Ile5Ser) causing X-linked DEE90. In addition, we review the genotype and phenotype of affected individuals with DEE90.
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Maternal Carbamazepine Therapy and Unusual Adverse Effects in a Breastfed Infant.
Antonucci, R, Cuzzolin, L, Manconi, A, Cherchi, C, Oggiano, AM, Locci, C
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2018;(2):155-157
Abstract
BACKGROUND Usually, no adverse effects are observed in breastfed infants whose mothers are treated with the anti-epileptic carbamazepine. In this article, we described unusual short-term adverse effects observed in a young infant after exposure to carbamazepine during pregnancy and lactation. CASE REPORT A 40-day-old female infant, born at term, was admitted to the Pediatric Clinic at University of Sassari, Italy, for recurrent regurgitations and vomiting. She was breastfed since birth and her mother was under chronic carbamazepine therapy. Gastroesophageal reflux was initially suspected; therefore, thickening of feeds and postural therapy were applied without any benefit. Subsequently, high levels of carbamazepine were detected in infant serum and in maternal breast milk. After an unsuccessful attempt to combine breastfeeding with formula feeding, the switch to exclusive formula feeding was made, with subsequent rapid resolution of symptoms and body weight increase. DISCUSSION AND CONCLUSIONS The use of carbamazepine is considered compatible with breastfeeding, even if the potential risk of adverse reactions in breastfed infants exists. In this case, the discontinuation of breastfeeding resulted in the complete resolution of symptoms, suggesting a correlation between the observed manifestations in the infant and her exposure to maternal therapy.
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A novel SLC1A4 homozygous mutation causing congenital microcephaly, epileptic encephalopathy and spastic tetraparesis: a video-EEG and tractography - case study.
Pironti, E, Salpietro, V, Cucinotta, F, Granata, F, Mormina, E, Efthymiou, S, Scuderi, C, Gagliano, A, Houlden, H, Di Rosa, G
Journal of neurogenetics. 2018;(4):316-321
Abstract
Biallelic mutations in the SLC1A4 gene have been identified as a very rare cause of neurodevelopmental disorders. l-serine transport deficiency has been regarded as the causal molecular mechanism underlying the neurological phenotype of SLC1A4 mutation patients. To date this genetic condition has been reported almost exclusively in a limited number of Ashkenazi-Jewish individuals and as a result the SLC1A4 gene is not routinely included in the majority of the genetic diagnostic panels for neurological diseases. We hereby report a 7-year-old boy from a Southern Italian family, presenting with epileptic encephalopathy, congenital microcephaly, global developmental delay, severe hypotonia, spasticity predominant at the lower limbs, and thin corpus callosum. Whole exome sequencing identified a novel segregating SLC1A4 gene homozygous mutation (c.1141G > A: p.Gly381Arg) as the likely cause of the disease in our family. In order to deeply characterize the electro-clinical and neurological phenotype in our index patient, long-term systematic video-electroencephalograms (EEG) as well as repeated brain imaging studies (which included tractographic reconstructions) were performed on a regular basis during a 7 years follow-up time. In conclusion, we suggest to carefully considering SLC1A4 biallelic mutations in individuals presenting an early onset severe neurodevelopmental disorder with variable spasticity and seizures, regardless the patients' ethnic background.
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Early Life Epilepsy and Episodic Apnea Revealing an ATP1A3 Mutation: Report of a Pediatric Case and Literature Review.
Younes, TB, Benrhouma, H, Klaa, H, Rouissi, A, Chaabouni, M, Kraoua, I, Youssef-Turki, IB
Neuropediatrics. 2018;(5):339-341
Abstract
ATP1A3 mutations have now been recognized in infants, children, and adults presenting with a diverse group of neurological phenotypes, including rapid-onset dystonia-parkinsonism, alternating hemiplegia of childhood, and most recently, cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome. The phenotypic spectrum of ATP1A3-related neurological disorders continues to expand. In this case study, we report on early life epilepsy with episodic apnea potentially secondary to ATP1A3 mutation in a Tunisian child.
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De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy.
Syrbe, S, Hedrich, UBS, Riesch, E, Djémié, T, Müller, S, Møller, RS, Maher, B, Hernandez-Hernandez, L, Synofzik, M, Caglayan, HS, et al
Nature genetics. 2015;(4):393-399
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Abstract
Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features. Using next-generation sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium channel KV1.2, in six isolated patients with epileptic encephalopathy (one mutation recurred three times independently). Four individuals presented with febrile and multiple afebrile, often focal seizure types, multifocal epileptiform discharges strongly activated by sleep, mild to moderate intellectual disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype showed almost complete loss of function with a dominant-negative effect. Two further individuals presented with a different and more severe epileptic encephalopathy phenotype. They carried mutations inducing a drastic gain-of-function effect leading to permanently open channels. These results establish KCNA2 as a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing neurons.
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Glucose transporter type 1 deficiency due to SLC2A1 gene mutations--a rare but treatable cause of metabolic epilepsy and extrapyramidal movement disorder; own experience and literature review.
Szczepanik, E, Terczyńska, I, Kruk, M, Lipiec, A, Dudko, E, Tryfon, J, Jurek, M, Hoffman-Zacharska, D
Developmental period medicine. 2015;(4):454-63
Abstract
THE AIM To present the molecular and clinical characteristics of three children with glucose deficiency syndrome, an inborn rare metabolic disease, caused by mutations in the SLC2A1 gene. MATERIAL AND METHODS The investigation was carried out in three children: two girls and one boy showing symptoms of GLUT1 deficiency syndrome (GLUT1-DS). They were referred for SLC2A1 gene analysis. RESULTS The presence of mutations in all of them was confirmed. Only point mutations were identified, two missenses p.Gly132Ser, p.Arg212Cys and amino acid insertion p.Ser_Val227insValProPro. In two cases the mutations arose de novo, one was heritable of paternal origin. CONCLUSIONS GLUT1-DS shows high clinical variability. It should be suspected in children of any age presenting with single features or a combination of any form of intractable epilepsy with seizures of various types, movement disorders and paroxysmal events, especially triggered by exercise, exertion, or fasting, and any unexplainable neurological deterioration. The basic diagnostic hallmarks of GLUT1-DS are CSF hypoglycorrhachia and lowered CSF/Blood serum glucose ratio. This is why lumbar punction should be considered more frequently than it is in practice being performed nowadays. Antiepileptic drug treatment may be ineffective or even potentially detrimental. Early identification and molecular confirmation of GLUT1-DS is important, because this is a metabolic disorder and patients should as soon as possible primarily be treated with a ketogenic diet.
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Dietary treatment of intractable epilepsy.
Cervenka, MC, Kossoff, EH
Continuum (Minneapolis, Minn.). 2013;(3 Epilepsy):756-66
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Abstract
PURPOSE OF REVIEW Dietary therapies for seizure management date back further than pharmacologic interventions, but many neurologists are not familiar with these treatment options. This introduction to dietary therapies will discuss administration of ketogenic diets, comparisons between diet types, evidence-based efficacy of diet therapies in epilepsy treatment, and management of side effects. This review will provide the general neurologist with the skills to identify appropriate candidates for these treatments and to offer comprehensive ongoing care. RECENT FINDINGS In adults and children with medically resistant epilepsy, studies have consistently shown a greater than 50% reduction in seizure frequency in approximately one-half of patients within days to months after starting dietary therapy. SUMMARY Dietary treatment options for epilepsy include the classic ketogenic diet, the medium-chain triglyceride diet, the modified Atkins diet, and the low glycemic index treatment. These were first used to control seizures in children with intractable epilepsy, but in recent years have also been demonstrated to be safe and effective in children and adults with a broad range of seizure types and are being used with increased frequency worldwide.
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Should we think of Urbach-Wiethe disease in refractory epilepsy? Case report and review of the literature.
Omrani, HG, Tajdini, M, Ghelichnia, B, Hosseini, SM, Tafakhori, A, Rahimian, E, Aghamollaii, V
Journal of the neurological sciences. 2012;(1-2):149-52
Abstract
Urbach-Wiethe disease (UWD) is an autosomal recessive disease characterized by both neurological and dermatological manifestations. Face specially eyelids are commonly involved. Alopecia, nail dystrophy and dental anomalies have been reported as less frequent symptoms. Some patients show evidences of epilepsy and psychiatric symptoms such as schizophrenia, mood disorders, and anxiety due to calcium deposits in different parts of the brain. In this report, we describe the case of a young woman affected by UWD presenting with neurological involvements and no dermatological manifestations. This patient is a unique case of UWD as she has partial seizures and hoarseness. Also we summarize relevant data from the literature.
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[Celiac disease with epilepsy and minor neurological disorders].
Tirotta, D, Eusebi, G, Durante, V
Recenti progressi in medicina. 2012;(5):198-204
Abstract
We present the case of a woman with abdominal pain, headache, syncope. The diagnosis of celiac disease (CD), associated with epilepsy and the brief review of literature, suggest that CD should be considered in neurological disorders of unknown etiology. The diet can be effective only on abdominal pain.
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Severe encephalopathy with epilepsy in an infant caused by subclinical maternal pernicious anaemia: case report and review of the literature.
Korenke, GC, Hunneman, DH, Eber, S, Hanefeld, F
European journal of pediatrics. 2004;(4-5):196-201
Abstract
UNLABELLED Vitamin B(12) deficiency is one of the major causes of megaloblastic anaemia with or without neurological symptoms. We report on a patient manifesting acute encephalopathy, epilepsy, microcephaly and megaloblastic anaemia at the age of 4 months. Vitamin B(12) deficiency in the patient was due to subclinical pernicious anaemia of the mother who exhibited neither haematological nor neurological symptoms. Mother and child both had elevated methylmalonic acid in their urine which is a sensitive parameter of vitamin B(12) deficiency. Vitamin B(12) therapy resulted in arrest of convulsions within 24 h. There were no further seizures although the patient showed moderate mental retardation at the age of 7 years but a normal head circumference. Long-term MRI follow-up, performed at the age of 7 years, showed moderate enlargement of the ventricles with reduction of myelin and hypoplasia of the corpus callosum. CONCLUSION Vitamin B(12) deficiency due to maternal pernicious anaemia should always be considered in the differential diagnosis of neurological symptoms in infants and especially in combination with megaloblastic anaemia. Since the age of onset and the duration of neurological symptoms may contribute to the development of long-term symptoms, early diagnosis and treatment is important for vitamin B(12) deficient children.