Onset In Early Childhood Research Articles

Reduktion der auf Spinnen bezogenen Ängste durch Psychoedukation bei 8- bis 9-jährigen Kindern – eine Pilotstudie

In Western societies spiders are among the least liked of all arthropods, eliciting feelings of fear and disgust. The clinical manifestation of this fear - spider phobia - is a common anxiety disorder. In most cases the disorder has an early onset in childhood. The symptoms show a chronic course and can persist into adulthood if not treated. Etiological models emphasize the role of modeling and negative information transmission for the acquisition of the disorder. Even though powerful psychotherapeutic methods exist, referral to treatment is rather uncommon for children. Often spontaneous remission is expected, but that is atypical. The current study developed a psychoeducative program on spiders for elementary school children and evaluated it on a sample of 36 children aged 8 to 10 years. The main goal of this pilot study was to test the feasibility of the program. The study showed a reduction of fear of spiders after psychoeducation in girls and boys with previously high or moderate fear of spiders. The program could become a valuable contribution to the prevention of spider phobia and should be evaluated in future controlled trials.

A novel homozygous mutation in the WNK1/HSN2 gene causing hereditary sensory neuropathy type 2.

Hereditary sensory and autonomic neuropathy type 2 is a rare disorder caused by recessive mutations in the WNK1/HSN2 gene located on chromosome 12p13.33. Phenotype of the patients is characterized by severe sensory loss affecting all sensory modalities. We report a novel homozygous Lys179fsX182 (HSN2); Lys965fsX968 (WNK1/HSN2) mutation causing an early childhood onset hereditary sensory and autonomic neuropathy type 2, with acromutilations in upper and lower limbs, and autonomic dysfunction. To the best of our knowledge this is the first genetically proven case of hereditary sensory and autonomic neuropathy type 2 originating from East Europe.

Stress among parents of children with attention deficit hyperactivity disorder, a Malaysian experience

Attention deficit hyperactivity disorder (ADHD) is a chronic debilitating illness with onset in early childhood. The objective of this study was to look at the impact of children with ADHD on their parents. All parents with children diagnosed as having ADHD attending the Psychiatry Adolescent and Child Unit, University Malaya were included in this study. Their parenting stress was assessed using the Parent Stress Index. A total of 95 parents participated in the study. The proportion of parents who reported significant stress in this study was much higher than in most studies (n = 69, 73%). Significant correlation was found between the severity of the child's disorder (Children's Global Assessment Scale [CGAS] score) and the parents' stress level (OR 0.16, 95% CI 0.05-0.51). Mothers were significantly more stressed than fathers (OR 0.16, 95% CI 0.05-0.51) and non-Malay parents more stressed than the Malay parents (OR 3.92, 95% CI 1.29-11.94). Parents with children older than 12 years of age were six times more stressed than parents with children younger than 12 years old (OR 6.47, 95% CI 1.55-27.01). Stressed parents acknowledged that having a child with ADHD was their biggest worry. Stress has marked consequences on any person and has important bearings on their mental health. Stress among parents needs be looked into when treating children with ADHD.

Early Onset Retinal Dystrophy Due to Mutations inLRAT: Molecular Analysis and Detailed Phenotypic Study

To report novel variants and characterize the phenotype associated with the autosomal recessive retinal dystrophy caused by mutations in the lecithin retinol acyltransferase (LRAT) gene. A total of 149 patients with Leber's congenital amaurosis (LCA) or early onset retinal dystrophy were screened for mutations in LCA-associated genes using an arrayed-primer extension (APEX) genotyping microarray (Asper Ophthalmics). LRAT sequencing was subsequently performed in this 148-patient panel. Patients identified with mutations underwent further detailed phenotyping. APEX analysis identified one patient with a previously reported homozygous LRAT mutation. Sequencing of the panel identified three additional patients with novel homozygous LRAT mutations in exon 2. All four patients had severe progressive nyctalopia, visual field constriction, and photophilia in childhood. Visual acuity ranged from 0.22 logMAR to hand motion. Funduscopy revealed severe retinal pigment epithelial atrophy and minimal retinal pigmentation. Asteroid hyalosis and macular epiretinal fibrosis were frequent. All demonstrated reduced fundus autofluorescence. Optical coherence tomography identified disrupted retinal lamination, outer-retinal debris, and an unidentifiable photoreceptor layer in two cases. Full-field electroretinograms were undetectable or showed severe rod-cone dysfunction. Photopic perimetry revealed severe visual field constriction. Dark-adapted perimetry demonstrated markedly reduced photoreceptor sensitivity. Dark-adapted spectral sensitivity measurements identified functioning rods in two of three patients. All three had severely reduced L- and M-cone sensitivity and poor color discrimination. LRAT mutations cause a severe, early childhood onset, progressive retinal dystrophy. Phenotypic similarities to the retinal dysfunction associated with RPE-specific protein 65 kDa mutations, another visual cycle gene, suggest that LRAT deficiency may show a good response to novel therapies.

Complete remission of seizures after corpus callosotomy

Corpus callosotomy is usually intended to alleviate-not to achieve total control of-epileptic seizures. A few patients experience complete seizure control after callosotomy, but the associated clinical factors are unknown. The object of this study was to investigate clinical factors associated with long-term seizure remission after total corpus callosotomy in patients with infantile or early childhood onset epilepsy. Thirteen consecutive patients with infantile or early childhood onset epilepsy underwent 1-stage total corpus callosotomy for alleviation of seizures. Their age at surgery ranged from 1 year and 5 months to 24 years (median 7 years). Eleven patients had West syndrome at the onset of disease, and the other 2 had Lennox-Gastaut syndrome. All patients suffered from spasms, axial tonic seizures, or atonic seizures. Six patients had proven etiology of epilepsy, including tuberous sclerosis, polymicrogyria, trauma, and Smith-Magenis syndrome. The association between postoperative seizure freedom and preoperative factors including age at surgery, no MRI abnormalities, proven etiology, and focal electroencephalographic epileptiform discharges was examined. Postoperative seizure freedom was achieved in 4 of 13 patients for a minimum of 12 months. All 4 patients had no MRI abnormalities and no identified etiology. None of the 8 patients with MRI abnormality, 6 patients with known etiology of epilepsy, or 4 patients aged older than 10 years at surgery achieved seizure freedom. Two of the 7 patients with focal electroencephalographic abnormalities became seizure free. Absence of MRI abnormalities was significantly associated with postoperative seizure freedom (p < 0.01). Complete seizure remission is achieved after total corpus callosotomy in a subgroup of patients with intractable epilepsy following West syndrome or Lennox-Gastaut syndrome. One-stage total corpus callosotomy at a young age may provide a higher rate of seizure freedom, especially for patients with no MRI abnormalities and no identified etiology of epilepsy.

Intra-articular Venous Malformations of the Knee

Intra-articular venous malformations (IAVM) of the knee represent a rare group of low-flow vascular malformations, mainly reported in the literature as synovial hemangiomas, usually with an onset in early childhood. The main symptoms and signs are knee pain, swelling, and hemarthrosis. These lesions are slowly progressive and can lead to chronic synovitis and joint damage. Confusing nomenclature and classification of these lesions have often led to misdiagnosis and inappropriate treatment. We report our experience in the treatment of 14 consecutive patients affected by knee IAVM. We carried out a retrospective study based on the review of the medical records and diagnostic imaging of the patients admitted to our department from October 1999 to June 2009, and discharged with the final diagnosis of IAVM of the knee. We observed 14 consecutive patients (8 boys, 6 girls); the median age at symptom onset was 5 years (range, 2.5 to 13 y). Magnetic resonance imaging was diagnostic in all cases. Surgical resection associated with a wide synoviectomy was the therapeutic procedure of choice in all cases. Within 6 months after surgery and physiotherapy, all the patients were symptom free with a full or at least acceptable knee range of motion. CD34 staining carried out in the last 7 cases of our series showed labeling of the endothelium of the thick-walled vessels, whereas the endothelium of the thin-walled vascular spaces was not stained. This finding of unstained vascular spaces suggests that a component of lymphatic vessels mixed with dysplastic blood vessels may be frequently present in these abnormalities. Magnetic resonance imaging plays a pivotal role in identifying the lesion. Surgical excision is always indicated and should be performed as early as possible to avoid lesion progression and to reduce the risk of chondral degeneration. According to the microscopic features of our resected specimens, we suggest that these lesions of the knee should be more properly named as IAVM instead of hemangiomas. Level IV.

Proteomic and Metabolomic Analyses of Mitochondrial Complex I-deficient Mouse Model Generated by Spontaneous B2 Short Interspersed Nuclear Element (SINE) Insertion into NADH Dehydrogenase (Ubiquinone) Fe-S Protein 4 (Ndufs4) Gene

Eukaryotic cells generate energy in the form of ATP, through a network of mitochondrial complexes and electron carriers known as the oxidative phosphorylation system. In mammals, mitochondrial complex I (CI) is the largest component of this system, comprising 45 different subunits encoded by mitochondrial and nuclear DNA. Humans diagnosed with mutations in the gene NDUFS4, encoding a nuclear DNA-encoded subunit of CI (NADH dehydrogenase ubiquinone Fe-S protein 4), typically suffer from Leigh syndrome, a neurodegenerative disease with onset in infancy or early childhood. Mitochondria from NDUFS4 patients usually lack detectable NDUFS4 protein and show a CI stability/assembly defect. Here, we describe a recessive mouse phenotype caused by the insertion of a transposable element into Ndufs4, identified by a novel combined linkage and expression analysis. Designated Ndufs4(fky), the mutation leads to aberrant transcript splicing and absence of NDUFS4 protein in all tissues tested of homozygous mice. Physical and behavioral symptoms displayed by Ndufs4(fky/fky) mice include temporary fur loss, growth retardation, unsteady gait, and abnormal body posture when suspended by the tail. Analysis of CI in Ndufs4(fky/fky) mice using blue native PAGE revealed the presence of a faster migrating crippled complex. This crippled CI was shown to lack subunits of the "N assembly module", which contains the NADH binding site, but contained two assembly factors not present in intact CI. Metabolomic analysis of the blood by tandem mass spectrometry showed increased hydroxyacylcarnitine species, implying that the CI defect leads to an imbalanced NADH/NAD(+) ratio that inhibits mitochondrial fatty acid β-oxidation.

Body Integrity Identity Disorder

IntroductionBody Integrity Identity Disorder (BIID) is a rare, infrequently studied and highly secretive condition in which there is a mismatch between the mental body image and the physical body. Subjects suffering from BIID have an intense desire to amputate a major limb or severe the spinal cord in order to become paralyzed. Aim of the study is to broaden the knowledge of BIID amongst medical professionals, by describing all who deal with BIID.MethodsSomatic, psychiatric and BIID characteristic data were collected from 54 BIID individuals using a detailed questionnaire. Subsequently, data of different subtypes of BIID (i.e. wish for amputation or paralyzation) were evaluated. Finally, disruption in work, social and family life due to BIID in subjects with and without amputation were compared.ResultsBased on the subjects' reports we found that BIID has an onset in early childhood. The main rationale given for their desire for body modification is to feel complete or to feel satisfied inside. Somatic and severe psychiatric co-morbidity is unusual, but depressive symptoms and mood disorders can be present, possibly secondary to the enormous distress BIID puts upon a person. Amputation and paralyzation variant do not differ in any clinical variable. Surgery is found helpful in all subjects who underwent amputation and those subjects score significantly lower on a disability scale than BIID subjects without body modification.ConclusionsThe amputation variant and paralyzation variant of BIID are to be considered as one of the same condition. Amputation of the healthy body part appears to result in remission of BIID and an impressive improvement of quality of life. Knowledge of and respect for the desires of BIID individuals are the first steps in providing care and may decrease the huge burden they experience.

Growth Factor Signaling Pathways in Lung Development and Cancer

Lung mesenchyme is a critical determinant of the shape and size of the lung, the extent and patterning of epithelial branching, the formation of the pulmonary vasculature, and the formation of mesenchymal components of the adult lung. Fibroblast Growth Factor 9 (FGF9) is expressed in developing lung epithelium and mesothelium and has an essential primary role in regulating mesenchymal growth and differentiation through signaling to mesenchymal FGF receptors (FGFRs) 1 and 2.Pleuropulmonary Blastoma (PPB) is a pediatric lung cancer syndrome with onset in late gestation and early childhood. PPB is a unique lung cancer in that its cellular origins are derived from lung mesenchyme. Germline loss‐of‐function mutations in Dicer1, an essential gene for the production of microRNAs, predisposes to PPB in humans. In this talk I will discus mechanisms by which FGF9 regulates mesenchymal growth and differentiation, evidence that Fgf9 may be regulated by microRNAs during lung development, and evidence that FGF9 may be an important factor for the initiation PPB.This work is funded by a grant from the March of Dimes foundation.

Leber Congenital Amaurosis Associated with AIPL1: Challenges in Ascribing Disease Causation, Clinical Findings, and Implications for Gene Therapy

Leber Congenital Amaurosis (LCA) and Early Childhood Onset Severe Retinal Dystrophy are clinically and genetically heterogeneous retinal disorders characterised by visual impairment and nystagmus from birth or early infancy. We investigated the prevalence of sequence variants in AIPL1 in a large cohort of such patients (n = 392) and probed the likelihood of disease-causation of the identified variants, subsequently undertaking a detailed assessment of the phenotype of patients with disease-causing mutations. Genomic DNA samples were screened for known variants in the AIPL1 gene using a microarray LCA chip, with 153 of these cases then being directly sequenced. The assessment of disease-causation of identified AIPL1 variants included segregation testing, assessing evolutionary conservation and in silico predictions of pathogenicity. The chip identified AIPL1 variants in 12 patients. Sequencing of AIPL1 in 153 patients and 96 controls found a total of 46 variants, with 29 being novel. In silico analysis suggested that only 6 of these variants are likely to be disease-causing, indicating a previously unrecognized high degree of polymorphism. Seven patients were identified with biallelic changes in AIPL1 likely to be disease-causing. In the youngest subject, electroretinography revealed reduced cone photoreceptor function, but rod responses were within normal limits, with no measurable ERG in other patients. An increasing degree and extent of peripheral retinal pigmentation and degree of maculopathy was noted with increasing age in our series. AIPL1 is significantly polymorphic in both controls and patients, thereby complicating the establishment of disease-causation of identified variants. Despite the associated phenotype being characterised by early-onset severe visual loss in our patient series, there was some evidence of a degree of retinal structural and functional preservation, which was most marked in the youngest patient in our cohort. This data suggests that there are patients who have a reasonable window of opportunity for gene therapy in childhood.

Early-onset versus typical childhood absence epilepsy; clinical and electrographic characteristics

PurposeChildhood absence epilepsy (CAE) is characterized by absence attacks with stereotyped electrographic discharges. Epidemiologic data concerning early-onset CAE is scarce. We tried to specifically analyze the early-onset CAE and compare it with typical CAE. MethodsIn this retrospective study, all patients with a clinical diagnosis of CAE were recruited in the outpatient epilepsy clinic at Shiraz University of Medical Sciences from 2008 to 2011. We considered the age of onset at four years or earlier as early-onset and above four years as typical CAE. Age, gender, age at seizure onset, seizure type(s), epilepsy risk factors, and EEG findings of all patients were registered routinely. Statistical analyses were performed using Chi square and Fisher's Exact tests. ResultsForty-six patients were diagnosed as having CAE. Sixteen patients (35%) had early-onset and 30 (65%) patients had typical CAE. Sex ratio (female to male) in early-onset was 7:9 and in typical CAE was 19:11 (P=0.2). Generalized tonic-clonic and myoclonic seizures were reported in both early-onset and typical CAE. The differences were not statistically significant. Epilepsy risk factors were similarly reported in both conditions. The EEG findings were similar in both groups. ConclusionWe did not observe any significant differences between early-onset and typical childhood absence epilepsies with respect to the demographic, clinical and electroencephalographic characteristics.

Childhood Ataxia with Cerebral Hypomyelination Syndrome: A Variant of Patient with Early Childhood Onset Related to EIF2B3 Mutation

Childhood ataxia with central nervous system hypomyelination (CACH) syndrome is an autosomal recessive transmitted leukodystrophy characterised by early childhood onset and acute deterioration following febrile illnesses or head trauma. We describe the case of a child with early onset of CACH syndrome. He presented with cerebellar ataxia beginning around two years of age with mild mental retardation. MRI showed diffuse white matter signal changes with thinning of the corpus callosum.

Early-onset Childhood Sarcoidosis with Incidental Multiple Enchondromatosis

The triad of rash, arthritis, and uveitis seems to be characteristic for early-onset childhood sarcoidosis. We describe an interesting case of early-onset childhood sarcoidosis coexisting enchondromatosis, which clinically masquerade as Langerhans cell histiocytosis. A 33 months old girl presented with skin rash, subcutaneous nodules with polyarthritis, and revealed the involvement of lymph nodes as well as spleen during work-up. She also presented with multiple osteolytic lesions which pathologically proven enchondromatosis. Oral prednisone was prescribed at 2 mg/kg/day for 2 months until when subcutaneous nodules and joint swellings almost disappeared, and then slowly tapered over a period of 5 months. We report an unusual case of early-onset childhood sarcoidosis presented with osteolytic bone lesions which were irrelevant to sarcoidosis.

Isolated Mitochondrial Complex I Deficiency: Explorative Data Analysis of Patient Cell Parameters

Mitochondrial dysfunction has been implicated in many human diseases and off-target drug effects. Isolated deficiency of mitochondrial complex I (CI), the first complex of the oxidative phosphorylation (OXPHOS) system, can arise from mutations in nuclear DNA (nDNA)-encoded subunits. In humans, these mutations are generally associated with neurodegenerative disorders like Leigh or Leigh-like syndrome with onset in early childhood. Currently, no cure or mitigative treatment is available for these diseases. To aid the future design of rational treatment strategies, insight into the pathophysiology of CI mutations is required. To this end, we quantitatively compared various cell physiological readouts between fibroblasts from healthy individuals and patients with isolated CI deficiency. Here we review how this multivariate dataset was obtained and in which way explorative data analysis (EDA) techniques can be used for pattern analysis. Based upon 13 experimental parameters two patient groups were identified. These displayed a later (cluster I) or earlier (cluster II) age of disease onset and death. Relative to cluster I, cluster II patient cells displayed a larger reduction in CI activity, a larger increase in NADH/ROS levels, mitochondrial fragmentation and lower cellular levels of OXPHOS proteins. Our results highlight a connection between CI deficiency, ROS and mitochondrial morphology/function. This information not only contributes to our understanding of the pathophysiological mechanism of CI and mitochondrial deficiency but also suggests possible targets for cellular intervention strategies.

The economics of screening infants at risk of hearing impairment: An international analysis

Objective Hearing impairment in children across the world constitutes a particularly serious obstacle to their optimal development and education, including language acquisition. Around 0.5–6 in every 1000 neonates and infants have congenital or early childhood onset sensorineural deafness or severe-to-profound hearing impairment, with significant consequences. Therefore, early detection is a vitally important element in providing appropriate support for deaf and hearing-impaired babies that will help them enjoy equal opportunities in society alongside all other children. This analysis estimates the costs and effectiveness of various interventions to screen infants at risk of hearing impairment. Methods The economic analysis used a decision tree approach to determine the cost-effectiveness of newborn hearing screening strategies. Two unique models were built to capture different strategic screening decisions. Firstly, the cost-effectiveness of universal newborn hearing screening (UNHS) was compared to selective screening of newborns with risk factors. Secondly, the cost-effectiveness of providing a one-stage screening process vs. a two-stage screening process was investigated. Results Two countries, the United Kingdom and India, were used as case studies to illustrate the likely cost outcomes associated with the various strategies to diagnose hearing loss in infants. In the UK, the universal strategy incurs a further cost of approximately £2.3 million but detected an extra 63 cases. An incremental cost per case detected of £36,181 was estimated. The estimated economic burden was substantially higher in India when adopting a universal strategy due to the higher baseline prevalence of hearing loss. The one-stage screening strategy accumulated an additional 13,480 and 13,432 extra cases of false-positives, in the UK and India respectively when compared to a two-stage screening strategy. This represented increased costs by approximately £1.3 million and INR 34.6 million. Conclusions The cost-effectiveness of a screening intervention was largely dependent upon two key factors. As would be expected, the cost (per patient) of the intervention drives the model substantially, with higher costs leading to higher cost-effectiveness ratios. Likewise, the baseline prevalence (risk) of hearing impairment also affected the results. In scenarios where the baseline risk was low, the intervention was less likely to be cost-effective compared to when the baseline risk was high.

Healthy babies through infant-centered feeding protocol: an intervention targeting early childhood obesity in vulnerable populations.

BackgroundPoor feeding practices during infancy contribute to obesity risk. As infants transition from human milk and/or formula-based diets to solid foods, these practices interfere with infant feeding self-regulation and healthy growth patterns. Compared with other socioeconomic groups, lower-income mothers are more likely to experience difficulty feeding their infants. This may include misinterpreting feeding cues and using less-than-optimal feeding styles and practices, such as pressuring infants during mealtimes and prematurely introducing solid food and sweetened beverages. The Healthy Babies trial aims to determine the efficacy of a community-based randomized controlled trial of an in-home intervention with economically and educationally disadvantaged mother-infant dyads. The educational intervention is being conducted during the infant's first 6 months of life to promote healthy transition to solids during their first year and is based on the theory of planned behavior.Methods/DesignWe will describe our study protocol for a multisite randomized control trial being conducted in Colorado and Michigan with an anticipated sample of 372 economically and educationally disadvantaged African American, Hispanic, and Caucasian mothers with infants. Participants are being recruited by county community agency staff. Participants are randomly assigned to the intervention or the control group. The intervention consists of six in-home visits by a trained paraprofessional instructor followed by three reinforcement telephone contacts when the baby is 6, 8, and 10 months old. Main maternal outcomes include a) maternal responsiveness, b) feeding style, and c) feeding practices. Main infant outcome is infant growth pattern. All measures occur at baseline and when the infant is 6 and 12 months old.DiscussionIf this project is successful, the expected outcomes will address whether the home-based early nutrition education intervention is effective in helping mothers develop healthy infant feeding practices that contribute to improving infant health and development and reducing the risk of early-onset childhood obesity.Trial RegistrationCurrent Controlled Trials ACTRN126100000415000

Early-onset childhood sarcoidosis: a case report

Sarcoidosis is a multisystemic granulomatous disease of unknown etiology and it most commonly affects young adults. Childhood sarcoidosis is relatively rare; older children usually present a picture similar to that of adults, with frequent hilar lymphadenopathy and pulmonary infiltration. Early-onset (<4 years of age) childhood sarcoidosis is a unique disease and has a different presentation. It is characterized by arthritis, uveitis, and cutaneous involvement. The prognosis of early-onset childhood sarcoidosis varies in different studies due to the rarity of the disease. The treatment of choice in systemic involvement of childhood sarcoidosis is corticosteroids. Methotrexate can also be considered in the long-term treatment due to its safety, effectiveness, and steroid-sparing effect in children.

Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation

Megalencephalic leucoencephalopathy with subcortical cysts is a genetic brain disorder with onset in early childhood. Affected infants develop macrocephaly within the first year of life, after several years followed by slowly progressive, incapacitating cerebellar ataxia and spasticity. From early on, magnetic resonance imaging shows diffuse signal abnormality and swelling of the cerebral white matter, with evidence of highly increased white matter water content. In most patients, the disease is caused by mutations in the gene MLC1, which encodes a plasma membrane protein almost exclusively expressed in brain and at lower levels in leucocytes. Within the brain, MLC1 is mainly located in astrocyte-astrocyte junctions adjacent to the blood-brain and cereborspinal fluid-brain barriers. Thus far, the function of MLC1 has remained unknown. We tested the hypothesis that MLC1 mutations cause a defect in ion currents involved in water and ion homeostasis, resulting in cerebral white matter oedema. Using whole-cell patch clamp studies we demonstrated an association between MLC1 expression and anion channel activity in different cell types, most importantly astrocytes. The currents were absent in chloride-free medium and in cells with disease-causing MLC1 mutations. MLC1-dependent currents were greatly enhanced by hypotonic pretreatment causing cell swelling, while ion channel blockers, including Tamoxifen, abolished the currents. Down regulation of endogenous MLC1 expression in astrocytes by small interfering RNA greatly reduced the activity of this channel, which was rescued by overexpression of normal MLC1. The current-voltage relationship and the pharmacological profiles of the currents indicated that the channel activated by MLC1 expression is a volume-regulated anion channel. Such channels are involved in regulatory volume decrease. We showed that regulatory volume decrease was hampered in lymphoblasts from patients with megalencephalic leucoencephalopathy. A similar trend was observed in astrocytes with decreased MLC1 expression; this effect was rescued by overexpression of normal MLC1. In the present study, we show that absence or mutations of the MLC1 protein negatively impact both volume-regulated anion channel activity and regulatory volume decrease, indicating that megalencephalic leucoencephalopathy is caused by a disturbance of cell volume regulation mediated by chloride transport.

CACP syndrome (Camptodactyly Arthropathy Coxa Vara Pericarditis). Clinical case

The CACP syndrome is characterized by congenital camptodactyly and early childhood onset of non inflammatory synovial hyperplasia. Some patients present with coxa vara, others with pericarditis, some have both of these symptoms.

Outcome and Prognostic Features in Opsoclonus-Myoclonus Syndrome From Infancy to Adult Life

Opsoclonus-myoclonus syndrome (OMS) is a serious and often chronically disabling neurologic illness with onset in early childhood. Our aim was to identify long-term neurologic sequelae of OMS and predictors for disease outcome. We retrospectively assessed the case records of 101 patients diagnosed with OMS over a 53-year period. Clinical data were obtained from medical record review; we documented age at onset, severity of symptoms, response to treatment, and neurocognitive sequelae. Overall, 21% of the patients had a neuroblastoma detected; however, in those born after 1990, this figure rose to 40%. Sixty-one percent of the patients had a chronic-relapsing course, 32% experienced several acute exacerbations, and 7% had a monophasic course. At the most recent review, 60% had residual motor problems, 66% speech abnormalities, 51% learning disability, and 46% behavior problems. One-third of the patients had normal intellectual outcome and cessation of symptoms. A severe initial presentation predicted a chronic disease course (odds ratio [OR]: 2.77 [95% confidence interval (CI): 1.47-5.23]; P = .002) and later learning disability (OR: 2.03 [95% CI: 1.08-3.79]; P = .026). Those with cognitive impairment were younger at disease onset (15.0 vs 19.5 months; P = .029). A chronic-relapsing disease course was associated with motor (P < .001), speech (P = .001), cognitive (P < .001), and behavior (P = .006) problems. OMS is a chronic and debilitating illness; those with severe initial symptoms and those who are very young at disease onset are at increased risk of developing long-term sequelae. It is important for affected children to be identified early, because they might benefit from targeted immunomodulating therapy in specialist centers.