311 research outputs found
HYPOTONIC INFANT: CLINICAL AND ETIOLOGICAL EVALUATION
Pediatri hekimlerinin özellikle yenidoğan döneminde sık karşılaştığı klinik tablolardan biriside hipotonidir. Hipotoniyi santral (beyin, beyin sapı ve servikal spinal bileşke) ve periferal hipotoni (ön boynuz hücreleri, periferik sinirler, nöromuskuler bileşke ve kaslar) olarak sınıflamak mümkündür. Ancak santral ve/veya periferal sinir sistemini etkileyebilen bazı multisistemik hastalıklar da klinik olarak hipotoni ile karşımıza çıkabilmektedirler. Hipotoniye neden olan durumların ortaya çıkartılmasında, nöroloji, genetik ve metabolizma bölümlerini içeren multidispliner yaklaşım gereklidir. Bu derlemede hipotoniye klinik yaklaşım ve sık görülen hipotoni nedenleri tartışılacaktır. Hypotonia is one of the frequent clinical finding that the pediatricians detected, especially in neonatal period. Hypotonia could be classified as central ( brain, brainstem and cervical spinal junction) and peripheral hypotonia (anterior horn cells, peripheral nerves, neuromuscular junction and muscles). However, multisystemic diseases that can affect central and/or peripheral nervous system may prove to a clinical hypotonia. Multidisciplinary approach is essential to detect the situations that can cause hypotonia, including neurology, genetic and metabolic disorders departments. In this study, the causes and the clinical approach to hypotonia were reviewed
ZONISAMIDE EXPERIENCE IN PATIENTS WITH REFRACTORY EPILEPSY
Amaç: Parsiyel epilepsisi bulunan, > 16 yaş hastalarda zonisamidin güvenilir ve etkin bir antiepileptik ilaç olduğu yapılan kontrollü çalışmalarla gösterilmiştir. Ancak literatürde zonisamidin çocuklarda kullanımı, etkinliği ve güvenilirliği ile ilgili yeterli sayıda çalışma bulunmamaktadır. Gereç ve yöntem: Ocak 2010-Aralık 2010 tarihleri arasında, diğer anti-epileptik ilaçlara yanıt alınamayan ve zonisamid tedavisi başlanan 10 dirençli epilepsi olgusunun tedavi sonuçları değerlendirilmiştir. Zonisamid, 2 mg/kg/gün ve 2 dozda başlanarak, haftalık 1-2 mg/kg/gün doz artışı yapılmış ve maksimum 12 mg/kg/gün dozunda kullanılmıştır. Bulgular: On hastanın (5 kız, 5 erkek) ortalama yaşı 9,7 yıl (min 4,7-max 17)'dir. 2/10 olgu idiyopatik, 3/10 olgu kriptojenik, 5/10 olgu semptomatik epilepsi olarak sınıflandırılmıştır. Tedavi süresi ortalama 6,9 aydır. Olguların 6/10'u jeneralize, 4/10'u parsiyel epilepsi hastasıdır. Jeneralize ve parsiyel epilepsi gruplarında birer olguda ≥ %50 tedavi yanıtı görüldü. Parsiyel epilepsi olarak sınıflandırılan 1 olgunun ise nöbetsiz olduğu tespit edilmiştir. Zonisamid tedavisi süresince sadece 1 olguda geçici iştahsızlık ve kilo kaybı görüldüğü saptanmıştır. Sonuç olarak, antiepileptik ilaçlara yanıt alınamayan, özellikle parsiyel epilepsisi bulunan olgularda zonisamid tedavisinin etkili ve güvenli bir tedavi seçeneği olduğunu düşünmekle beraber daha çok olguyu kapsayan çalışmalarla desteklenmesi gerektiği kanaatindeyiz. Objeçtive: It have shown with controlled studies that, zonisamide is a safe and effective antiepileptic drug in > 16 years of age patients with partial epilepsy. However, there is not enough study on the efficacy and safety of the use zonisamide with children, in literature. Material and method: The treatment results of 10 cases with refractory epilepsy, not responded to the other anti-epileptic drugs and zonisamide therapy was initiated, between January 2010-December 2010, were evaluated, The starting dose of zonisamide was 2 mg / kg / day, dose has been increased weekly by 1-2 mg / kg / day and a maximum of 12 mg / kg / day was used. Results: Ten patients (5 boys, 5 girls), mean age was 9.7 years (min 4.7-max 17 years). 2/ 10 of the cases idiopathic, 3 / 10 of the cases cryptogenic and 5 / 10 of the cases were classified as symptomatic epilepsy. The mean duration of treatment was 6.9 months. 6 / 10 of the cases were generalized and 4 / 10 of the cases were partial epilepsy patient. In each generalized and partial epilepsy groups, ≥ 50% treatment response was seen in one patients. One case who had been classified as partial epilepsy was found as seizure free. In only 1 case, temporary loss of appetite and weight loss was seen during zonisamide therapy. As a result, we thought that zonisamide is effective and safe treatment option, particularly in patients with partial epilepsy who did not respond to other antiepileptic drugs, but more studies are needed to support
IS ROLANDIC EPILEPSY ALWAYS A BENIGN DISEASE?
Rolandik epilepsi, çocukluk çağının sık görülen parsiyel epilepsisidir. Genellikle uykuda gelişen fokal ya da sekonder jeneralize nöbetler görülür. Elektroensefalografide, tek taraflı ya da bilateral sentro-temporal diken dalga deşarjlarının varlığı karakteristiktir. Olguların çoğunda, adolesan dönemde elektroensefalografik ve klinik bulguların normale dönmesi nedeniyle iyi seyirli olarak kabul edilmektedir. Nöbetlerin seyrek olarak görülmesi ve iyi prognozu nedeniyle anti-epileptik tedavi başlanması tartışmalıdır. Bu makalede Rolandik epilepsi bulguları ile izlenen, takipte uykunun elektriksel status epileptikusu, dil, ince motor ve kişisel sosyal alanlarda baskılanma bulguları gelişen bir olgu Rolandik epilepsi seyrinin her zaman iyi huylu olmayabileceğine dikkat çekmek amacıyla sunulmuştur Rolandic epilepsy is a common childhood partial epilepsy. Focal or secondary generalized seizures during sleep are usually developed. On electroencephalography, unilateral or bilateral presence of the centro-temporal spike-wave discharges are characteristic. In most cases, electroencephalographic and clinical findings are return to normal in adolescent period and is considered as a good prognosis. Due to the rare seizures and good prognosis treat with anti-epileptic therapy is controversial. In this study, we presented a patient with Rolandic epilepsy, who developed electrical status epilepticus during sleep, suppression of language, fine motor, and personal social areas to keep attention to the course of Rolandic epilepsy may not be always good-nature
TAY-SACHS HASTALIĞI BULUNAN BİR ERKEK ÇOCUĞUNDA MANYETİK REZONANS GÖRÜNTÜLEME BULGULARI
Tay-Sachs is a neurodegenerative lysosomal storage disease that is caused by the mutations in the HEXA gene. Decreased ß-hexosaminidase A activity leads to the accumulation of the GM2 gangliosides in neuron cytoplasms and causes progressive neurologic dysfunction. Magnetic resonance imaging findings drastically change during the progression of the disease. At the early stage of the disease T2 weighted images demonstrate hyperintense lesions in basal ganglia or non-specific findings. In the late phase of the disease cerebral and cerebellar atrophy, and basal ganglia and white matter T2 hyperintensities can be seen. In this paper, we reported a 17 month-old boy with Tay-Sachs disease whose clinical and magnetic resonance imaging findings progressed in 5 months period. Tay-Sachs HEXA genindeki mutasyonların neden olduğu nörodejeneratif bir lizozomal depo hastalığıdır. ß-heksosaminidaz A aktivitesinin düşüklüğü nedeniyle nöron sitoplazmalarında GM2 gangliozid birikimi ve bunun sonucunda da ilerleyici nörolojik disfonksiyon gelişir. Hastalığın progresyonu ile birlikte beyin manyetik rezonans görüntüleme bulguları da dramatik olarak değişir. Hastalığın erken dönemlerinde bazal ganglionlarda T2 ağırlıklı görüntülerde belirgin hiperintens lezyonlar ya da spesifik olmayan bulgular görülebilir. Hastalığı geç dönemlerinde ise serebral ve serebellar atrofi, bazal ganglion ve beyaz cevherde T2 hiperintens lezyonlar görülebilir. Bu makalede 5 aylık bir sürede klinik ve manyetik rezonans görüntüleme bulguları ilerleyen 17 aylık bir TAY-Sachs hastalığı olgusu sunulmuştu
COL4A1-related autosomal recessive encephalopathy in 2 Turkish children.
OBJECTIVE: This study presents the neurologic phenotypes of 2 brothers with a novel homozygous COL4A1 mutation that was identified in a large Turkish consanguineous cohort of neurogenetic diseases. METHODS: Whole-exome sequencing and bioinformatic analysis of consanguineous families with children affected by early-onset, neurogenetic disorders was performed using the RD-Connect Genome-Phenome Analysis Platform. We also performed clinical, EEG, and neuroimaging analyses in unaffected siblings and parents. RESULTS: We have identified a homozygous missense mutation in COL4A1 (p.Gly1278Ser, NM_001845.5:c.3832G>T) in 2 siblings affected by small vessel brain disease with periventricular leukoencephalopathy and ocular defects. Presenting symptoms included mild weakness, hemiparetic gait, pyramidal findings, and seizures, whereas their intellectual and behavioral functions were normal. Both parents and 5 of the siblings (3 boys and 2 girls) were heterozygous for the variant. They did not show any clinical or laboratory signs of small vessel disease. CONCLUSIONS: COL4A1 has previously been associated with dominant small vessel disease of the brain and other organs, manifesting with high penetrance in heterozygous mutation carriers. Our findings provide evidence that COL4A1-related encephalopathy can be inherited in an autosomal recessive manner, which is important for counseling, prognosis, and treatment. Genotype-phenotype correlations remain to be established
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Dihydropyridine Receptor Congenital Myopathy In A Consangineous Turkish Family.
Dihydropyridine receptor congenital myopathy is a recently described congenital myopathy caused by dominant or recessive mutations in the CACNA1S gene. To date, only 11 cases from 7 families were described in a single report. Here, we describe a consanguineous family with three affected children, presenting congenital hypotonia, contractures, ophthalmoplegia and respiratory insufficiency, with a novel homozygous mutation in the CACNA1S gene. They also showed cognitive delay, pes equinovarus deformity and neurogenic changes that have not been associated with this myopathy in the previous reports. This report expands the phenotypic spectrum of dihydropyridine receptor congenital myopathy and underscores the importance of whole exome sequencing in early onset neuromuscular disorders
Novel insights into PORCN mutations, associated phenotypes and pathophysiological aspects.
BACKGROUND: Goltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants. RESULTS: We report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes. CONCLUSIONS: Our combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS
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Novel insights into PORCN mutations, associated phenotypes and pathophysiological aspects.
BACKGROUND: Goltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants. RESULTS: We report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes. CONCLUSIONS: Our combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS
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Autosomal recessive variants in TUBGCP2 alter the γ-tubulin ring complex leading to neurodevelopmental disease.
Microtubules help building the cytoskeleton of neurons and other cells. Several components of the gamma-tubulin (γ-tubulin) complex have been previously reported in human neurodevelopmental diseases. We describe two siblings from a consanguineous Turkish family with dysmorphic features, developmental delay, brain malformation, and epilepsy carrying a homozygous mutation (p.Glu311Lys) in TUBGCP2 encoding the γ-tubulin complex 2 (GCP2) protein. This variant is predicted to disrupt the electrostatic interaction of GCP2 with GCP3. In primary fibroblasts carrying the variant, we observed a faint delocalization of γ-tubulin during the cell cycle but normal GCP2 protein levels. Through mass spectrometry, we observed dysregulation of multiple proteins involved in the assembly and organization of the cytoskeleton and the extracellular matrix, controlling cellular adhesion and of proteins crucial for neuronal homeostasis including axon guidance. In summary, our functional and proteomic studies link TUBGCP2 and the γ-tubulin complex to the development of the central nervous system in humans
Severe neurodevelopmental disease caused by a homozygous TLK2 variant
Abstract: A distinct neurodevelopmental phenotype characterised mainly by mild motor and language delay and facial dysmorphism, caused by heterozygous de novo or dominant variants in the TLK2 gene has recently been described. All cases reported carried either truncating variants located throughout the gene, or missense changes principally located at the C-terminal end of the protein mostly resulting in haploinsufficiency of TLK2. Through whole exome sequencing, we identified a homozygous missense variant in TLK2 in a patient showing more severe symptoms than those previously described, including cerebellar vermis hypoplasia and West syndrome. Both parents are heterozygous for the variant and clinically unaffected highlighting that recessive variants in TLK2 can also be disease causing and may act through a different pathomechanism
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