Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study.

BACKGROUND: Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. METHODS: In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RESULTS: Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively. CONCLUSION: Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients.

A rare concurrence: gelastic seizures in a patient with right temporal nongalenic pial arteriovenous fistula.

INTRODUCTION: Gelastic seizures are the type of seizures that are most commonly seen in childhood and should be excluded definitely in the differential diagnosis of hypothalamic hamartomas. This seizure type may be accompanied by refractory seizures, cognitive decline, and early puberty. However, etiology may also include other causes different than hypothalamic hamartomas. The seizure may also arise from temporal and frontal region, in addition to hypothalamus. Different clinical findings may be observed based on origin and areas of spread. CONCLUSIONS: In this article, we report a case of gelastic seizure that has been observed by a different cause other than hypothalamic hamartoma which was reported for the first time in the literature.

A rare concurrence: Antibodies against Myelin Oligodendrocyte Glycoprotein and N-methyl-d-aspartate receptor in a child.

BACKGROUND: Myelin Oligodendrocyte Glycoprotein antibodies (MOG) may be used as a biomarker for diagnosis of many demyelinating diseases. Especially, patients of acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), aquaporin-4 (AQP4) seronegative neuromyelitis optica spectrum disorder (NMOSD), monophasic or recurrent optic neuritis (ON), transverse myelitis and N-methyl-d-aspartate (NMDA) receptor encephalitis (NMDARe) can overlap with Myelin Oligodendrocyte Glycoprotein antibodies. We present a child with autoimmune encephalitis in whom antibodies against Myelin Oligodendrocyte Glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) were simultaneously detected. The clinical manifestation was characteristic of NMDAR encephalitis, and cranial and spinal magnetic resonance imaging showed no signs of encephalomyelitis. On the other hand, complete recovery within first days of steroid treatment was more compatible with the course of MOG antibody-related disease. CONCLUSIONS: We emphasize the rarity of this antibody combination in children and suggest these patients, although clinically improved, may require longer follow-up due to the risk of recurrence of two autoimmune disorders.

Lethal neonatal rigidity and multifocal seizure syndrome with a new mutation in BRAT1.

Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal (RMFSL) (OMIM# 614498) is a rare and recently characterized epileptic encephalopathy that is related to variants in the BRAT1 gene (Breast Cancer 1-associated ataxia telangiectasia mutated activation-1 protein). In this report, an RMFSL case, who died in the 10th month of the life, with rigidity, drug-resistant myoclonic seizures in the face and extremities, with, significant motor delays is presented. The exon sequence was determined and a new homozygous variant (C.2230_2237dupAACATGC) was detected. This RMFSL case with a homozygous variant in the BRAT1 gene, is the fourth one in the literature and the first one being reported from a Turkish family.

Neuroleptic Malignant Syndrome Associated with Valproate in an Adolescent.

Neuroleptic malignant syndrome (NMS) is a life-threatening idiosyncratic reaction that usually occurs after the administration of antipsychotic drugs. Antidepressants, benzodiazepines, and antiepileptic drugs are also suggested to be associated with NMS. It is believed to result from a dopaminergic blockade in the central nervous system. NMS is manifested by hyperthermia, muscle rigidity, autonomic dysfunction, altered mental status, leukocytosis, and elevated serum creatinine phosphokinase. Valproate is commonly used in the treatment of many psychiatric and neurologic disorders. Valproate can precipitate NMS, especially when used with antipsychotic drugs concurrently. A 17-year-old male patient, who presented with fever, muscular rigidity, confusion, sweating, and tachycardia was admitted to the emergency room. He had been taking only valproate for the last two months for bipolar disorder. His laboratory analyses revealed raised serum hepatic enzymes, creatinine phosphokinase, and myoglobin levels. Considering fever, rigidity, autonomic dysfunction, cognitive alteration, and high creatinine phosphokinase levels, the patient was diagnosed with NMS. In this paper, we aim to discuss the association between valproate and NMS.

UNUSUAL CLINICAL CASES THAT MIMIC ACUTE DISSEMINATED ENCEPHALOMYELITIS.

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated monophasic inflammatory demyelinating disorder of the central nervous system which poses a diagnostic challenge. We report on six cases of different etiologies that mimicked the clinical and radiologic findings of ADEM. The cases were collected from four different reference hospitals in Turkey. The same radiologist from the Akdeniz University Faculty of Medicine examined the magnetic resonance images of all patients. Three (50%) patients had antecedent infections. Initial symptoms of the patients were as follows: fever in 50%, altered consciousness in 33.3% and convulsions in 16.7% of patients. Neurologic examination showed long tract signs in 83.3%, ataxia in 50% and altered consciousness in 50% of patients. Cerebrospinal fluid examination revealed lymphocytic pleocytosis only in case 6. Four patients received steroid pulse therapy and one of these initially underwent intravenous immunoglobulin therapy. The patients' definitive diagnoses were as follows: paraspinal neuroblastoma-associated paraneoplastic syndrome; histiocytic sarcoma; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes; and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in one patient each, while two patients had hemophagocytic syndrome. The present case series demonstrated difficulties in diagnosing ADEM while revealing extremely rare disorders that mimic ADEM radiologically and clinically.

Evaluation of Neurodevelopment Using Bayley-III in Children with Cyanotic or Hemodynamically Impaired Congenital Heart Disease.

OBJECTIVE: The purpose of this study was to compare neurological development of children with cyanotic or hemodynamically impaired congenital heart disease (CHD) and healthy controls by using "Bayley Scales of Infant and Toddler Development Screening Test, Third Edition" (Bayley-III). PATIENTS: Children with CHD (n = 37) and healthy controls (n = 24) aged between 1 and 41 months who were admitted to the Department of Pediatric Cardiology at our university hospital were included. The participants were assessed using Bayley-III test. All patients had cyanotic or hemodynamically impaired CHD. Weight, height, body mass index (BMI), mid-arm circumference (MAC), triceps skinfold thickness (TSF), and head circumference (HC) were measured and standard deviation scores (SDSs) were determined. RESULTS: SDS values of weight, height, BMI, MAC, and TSF of the patients as well as HC values were significantly lower than the control group (P < .001). Compared with controls, the patients had significantly lower mean scores in all Bayley-III subscales (P < .001). We observed similar results in Bayley-III scores including the mean values of cognitive, language, and global motor scores for the CHD patients with and without cardiac surgery (P > .05). CONCLUSION: This study demonstrated that children with cyanotic or hemodynamically impaired CHD have delayed neurodevelopmental outcomes compared with healthy children as assessed using Bayley-III.

Potassium bromide for treatment of malignant migrating partial seizures in infancy.

BACKGROUND: The syndrome of malignant migrating partial seizures in infancy is a rare epileptic syndrome with a devastating course characterized by early onset of continuous pharmacoresistent multifocal seizures arising from multiple independent sites of both hemispheres with unknown etiology. PATIENT: A 2-month-old boy with the characteristic clinical and electroencephalograph pattern of migrating partial seizures in infancy was treated with potassium bromide. His seizures were unresponsive to the conventional and new generation antiepileptic drugs. RESULTS: The seizure frequency was reduced markedly with potassium bromide. CONCLUSIONS: Potassium bromide, an old antiepileptic drug, is useful in the treatment of malignant migrating partial seizures in infancy.

Simultaneous papilledema and optic disc drusen in a child.

Idiopathic intracranial hypertension is a headache syndrome characterized by elevated intracranial pressure with normal cerebrospinal fluid content, normal cranial imaging, and elevated appearance of the optic disc. We report on a 6.5-year-old boy with complaints of headache and right esotropia causing diplopia. A lumbar puncture indicated an opening cerebrospinal fluid pressure of 28 cm H(2)O. The headache, diplopia, and esodeviation resolved after the lumbar puncture. However, at 2-week follow-up, the elevated appearance of the optic disc continued despite normal cerebrospinal fluid pressure. A second ophthalmologic consultation revealed optic disc drusen, as also demonstrated by ocular ultrasonography. To date, two such cases have been reported in the literature. To our knowledge, this patient is the youngest with coexisting optic disc drusen and idiopathic intracranial hypertension.

Neuroleptic malignant syndrome due to risperidone misdiagnosed as status epilepticus.

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal disease characterized by fever, muscle rigidity, delirium and autonomic instability. Here we report a child, with NMS due to the risperidone misdiagnosed as status epilepticus. Nine year old boy, who had been under high dose risperidone treatment for 8 weeks, admitted to the emergency room because of the contractions (evaluated as status epilepticus) persisting for 7 hours. Since there was neuroleptic treatment in the past medical history and, unconsciousness, muscular rigidity, diaphoresis, hypertermi and, hypotension in physical examination, leucocytosis and elevated creatininphosphokinase levels in laboratory tests, the patient was evaluated as NMS and discharged without any complications. We reported this case to point out that; NMS may be misdiagnosed as status epilepticus in children when EEG monitoring is unavailable. When a child admitted to the emergency room because of suspicious convulsion neuroleptic drug use must surely be asked.

Evaluation of growth and neurodevelopment in children with congenital heart disease.

BACKGROUND: Children with congenital heart disease are under risk of delayed growth and development. We evaluated physical growth parameters and neurodevelopment in these patients in comparison with normal children and examined the effect of hemodynamic status. METHODS: Patients with congenital heart disease (n= 76) and healthy children (n= 51) aged 1-72 months applied to Mersin University Hospital, Mersin, Turkey were included. Patients with heart failure and those requiring intervention or surgery were classified as hemodynamically impaired (HI group, n= 30), and the others, hemodynamically normal (HN group, n= 46). Growth parameters including weight, height, body mass index (BMI), mid-arm circumference (MAC), and triceps skin fold thickness (TSF) were measured and standard deviations (SD) were determined. Functional development was assessed by Denver Developmental Screening Test-II (DDST II). RESULTS: MAC and BMI values of the group with impaired hemodynamic status were significantly lower than the hemodynamically normal and control groups (MAC P < 0.05 and BMI P < 0.01). In the DDST II, the group with hemodynamic abnormality had more failures in gross motor and fine motor skills than HN group and controls (gross motor P= 0.011, P < 0.001 and fine motor P= 0.028, P= 0.001, respectively) and more failures in language development than the control group (P= 0.001). CONCLUSION: The results showed the importance of hemodynamic status in growth and neurodevelopment of children with congenital heart disease. Besides routine growth parameters, more detailed examinations such as BMI, MAC, TSF, and developmental screening tests appear useful in identifying children with cardiac disease who are under risk for delayed growth and development.

Uncommon associations with ataxia-telangiectasia: vitiligo and optic disc drusen.

Ataxia-telangiectasia (A-T) is an autosomal recessive condition presented by progressive cerebellar ataxia, oculocutaneous telangiectasia, humoral and cellular immunodeficiencies and a predisposition to malignancy. We report on a 13 years old male patient with the diagnosis of A-T associated with uncommon clinical features; optic disc drusen and vitiligo. To our knowledge, this is the first report of A-T associated with these findings.

Role of apoptosis in Duchenne's muscular dystrophy.

We investigated the presence of apoptosis in muscle tissues from 24 patients (average age 5.44 +/- 1.81 years) with Duchenne's muscular dystrophy by in situ tailing of nuclear fragmentation. Muscle tissue from 4 children without histologic evidence of myopathy served as normal controls. Muscle fibers positive for nuclear DNA fragmentation were determined quantitatively by counting an area of at least 400 muscle fibers. Eleven of 24 specimens showed no nuclei with DNA fragmentation. On the other hand, 0.37 +/- 0.48% of fibers in patients with Duchenne's muscular dystrophy and none in controls had DNA fragmentation (P > .05). In this study, the percentage of apoptotic nuclei was higher in Duchenne's muscular dystrophy muscle than in normal controls. However, the difference did not reach a statistically significant level, and further studies with larger control groups are warranted.