Postural control before and after transitional locomotor tasks in children on the autism spectrum: A case-control study.

BACKGROUND: Instrumented measurements of postural control provide a more accurate insight into the motor development of children with autism. This study aimed to identify postural control deficits in autistic children during quiet standing before and after transient locomotor task. It was hypothesized that the parameters that characterize the trajectory of center of foot pressure (COP) displacement would be higher in autistic children compared to typically developing children. METHODS: Sixteen autistic children aged 6-10 but without a comorbidity diagnosis, were enrolled in the study group. The control group comprised 16 typically developing peers. The assessment of the transitional task comprised four different conditions: unperturbed and perturbed transition, stepping up, and stepping down tasks. Analysis of the COP signal was carried out for three distinct phases, i.e., phase 1 - quiet standing before step initiation, phase 2 - transit, and phase 3 - quiet standing until measurement completion. FINDINGS: The two-way ANOVA with a 2 × 4 factorial design (group × testing condition) revealed a group effect on all posturographic variables in the antero-posterior and medio-lateral directions of phase 1 and in the antero-posterior direction of phase 3. The Bonferroni post-hoc test showed the means of all those variables were significantly higher for the autistic than for typically developing children. Group allocation also had an effect on the time of transit and step length, which turned out to be significantly longer in autistic children compared to healthy peers. INTERPRETATION: Autistic children show increased postural sway before and after transitional locomotor tasks compared to typically developing children. The trial was prospectively registered in the Australian and New Zealand Clinical Trials Registry (no. ACTRN12621001113842; date registered: 23.08.2021).

Expanding the Knowledge of KIF1A-Dependent Disorders to a Group of Polish Patients.

BACKGROUND: KIF1A (kinesin family member 1A)-related disorders encompass a variety of diseases. KIF1A variants are responsible for autosomal recessive and dominant spastic paraplegia 30 (SPG, OMIM610357), autosomal recessive hereditary sensory and autonomic neuropathy type 2 (HSN2C, OMIM614213), and autosomal dominant neurodegeneration and spasticity with or without cerebellar atrophy or cortical visual impairment (NESCAV syndrome), formerly named mental retardation type 9 (MRD9) (OMIM614255). KIF1A variants have also been occasionally linked with progressive encephalopathy with brain atrophy, progressive neurodegeneration, PEHO-like syndrome (progressive encephalopathy with edema, hypsarrhythmia, optic atrophy), and Rett-like syndrome. MATERIALS AND METHODS: The first Polish patients with confirmed heterozygous pathogenic and potentially pathogenic KIF1A variants were analyzed. All the patients were of Caucasian origin. Five patients were females, and four were males (female-to-male ratio = 1.25). The age of onset of the disease ranged from 6 weeks to 2 years. RESULTS: Exome sequencing identified three novel variants. Variant c.442G>A was described in the ClinVar database as likely pathogenic. The other two novel variants, c.609G>C; p.(Arg203Ser) and c.218T>G, p.(Val73Gly), were not recorded in ClinVar. CONCLUSIONS: The authors underlined the difficulties in classifying particular syndromes due to non-specific and overlapping signs and symptoms, sometimes observed only temporarily.

Polish recommendations for diagnosis and therapy of paediatric stroke.

Stroke remains one of the greatest health challenges worldwide, due to a high mortality rate and, despite great progress in its treatment, the significant disability that it causes. Studies conducted around the world show that the diagnosis of stroke in children is often significantly delayed. Paediatric ischaemic arterial stroke (PAIS) is not only a problem that varies greatly in frequency compared to the adult population, it is also completely different in terms of its risk factors, clinical course and outcome. The main reason for the lack of a rapid diagnosis of PAIS is a lack of access to neuroimaging under general anaesthesia. The insufficient knowledge regarding PAIS in society as a whole is also of great importance. Parents and carers of children should always bear in mind that paediatric age is not a factor that excludes a diagnosis of stroke. The aim of this article was to develop recommendations for the management of children with acute neurological symptoms suspected of ischaemic stroke and further treatment after confirmation of the ischaemic aetiology of the problem. These recommendations are based on current global recommendations for the management of children with stroke, but our goal was also to match them as closely as possible to the needs and technical diagnostic and therapeutic possibilities encountered in Poland. Due to the multifactorial problem of stroke in children, not only paediatric neurologists but also a neurologist, a paediatric cardiologist, a paediatric haematologist and a radiologist took part in the preparation of these recommendations.

Modulation of center-of-pressure signal in children on the autism spectrum: A case-control study.

BACKGROUND: Proper postural and motor control plays a fundamental role in the child's ontogenetic development. So far, the postural control in children on the autism spectrum has mainly been assessed with standard posturographic measurements of center of pressure (COP) displacements. RESEARCH QUESTION: What are the differences in postural control between autistic and typically developing children? METHODS: The study group comprised 16 autistic children aged 6-10 years, identified by a psychiatrist. The control group consisted of 16 typically developing children aged 6-10 years with no posture deformities, no pervasive developmental disorder and no history of postural control or movement deficits. The data were collected during quiet standing with eyes open using a force plate. To gain a better insight into the postural control processes, the rambling-trembling and sample entropy analyses were used in COP data processing. RESULTS: Compared to typically developing children, those with autism spectrum had significantly higher values of COP and rambling trajectory parameters in the antero-posterior direction during quiet standing. The variables of the trembling trajectory did not differ significantly between the groups. The autistic children had significantly lower values of sample entropy in the antero-posterior direction compared to typically developing children. SIGNIFICANCE: More advanced measures of COP displacements including the rambling-trembling method and sample entropy revealed differences in postural control between autistic and typically developing children. These methods may therefore contribute to functional assessment of postural control deficits in children on the autism spectrum.

The Clinical and Epidemiological Profile of Paediatric-Onset Multiple Sclerosis in Poland.

Background. Paediatric-onset MS (POMS) has a unique clinical profile compared to the more prevalent adult-onset MS. For this study, we aimed to determine the demographic and clinical characteristics of POMS in Poland as well as addressing some of its epidemiological aspects. Methods. A retrospective study was conducted based on the Polish Multiple Sclerosis Registry, considering a population of children and adolescents with MS (age ≤ 18 years). Data were collected by all 13 centres across Poland specializing in diagnosing and treating POMS. The actual course of the disease and its clinical properties were compared between child (≤12 years) and juvenile (>12 years) patients. MS onset and its prevalence were assessed at the end of 2019, stratified by age range. Results. A total of 329 paediatric or juvenile patients (228 girls, 101 boys) with a clinically definite diagnosis of MS, in conformity with the 2017 McDonald Criteria, were enrolled. For 71 children (21.6%), the first symptoms appeared before the age of 12. The female: male ratio increased with age, amounting to 1:1 in the ≤12 years group and to 2.9:1 in the >12 years group. In most cases, the disease had multi-symptomatic onset (31.3%), and its course was mostly of a relapsing−remitting character (95.7%). The initial Expanded Disability Status Score for both groups was 1.63 ± 1.1, whereas the annual relapse rate was 0.84 during the first 2 years. The time between the onset of symptoms and diagnosis was longer in the younger patients (8.2 ± 4.2 vs. 4.6 ± 3.6 months; p < 0.005). On 31 December 2019, the age-adjusted prevalence standardized to the European standard population was 5.19/100,000 (95% CI, 4.64−5.78). Significantly higher prevalence was noted in the 13−18 years group (7.12; 95% CI, 6.64−7.86) than in the 9−12 years group (3.41; 95% CI, 2.98−3.86) and the <9 years group (0.56; 95% CI, 0.46−0.64; p < 0.001). Conclusion. POMS commencing at the age of ≤12 years is rare, differing significantly from the juvenile-onset and adult MS in terms of clinical characteristics, course, and incidence, as stratified by gender.

A Dialogue in the Medical Perspective-Body Mass and Nutritional Status Disorders during the Development Period.

Eating disorders among children and youth are a serious social problem. The time of development is the starting point in shaping eating patterns. Proper nutrition provides the basis for psychophysical development. A knowledgeable pediatrician can improve society's health by engaging parents and, later, the child or youth. We offer knowledge on the nutrition basics and the commonly available tools to assess the nutritional status. We will discuss the characteristics of eating and body mass disorders in developing children. We will provide information on the warning signals of eating and body mass disorders and recommend prophylaxis. The reader will be familiarized with the motivational dialogue as an effective control tool for the discussed health issues.

Pediatric-onset multiple sclerosis in Poland: A registry-based retrospective cohort study.

BACKGROUND: Epidemiologic data on pediatric-onset multiple sclerosis (POMS) in Central and Eastern Europe are limited. The aim of this study was to determine the incidence, prevalence and the clinical features of POMS in Poland. METHODS: Registry-based retrospective study was conducted among Polish children population (age ≤ 18 years), between 1 January 2010 and 31 December 2019. A total of 329 pediatric or juvenile patients fulfilled the International Pediatric MS Study Group (IPMSSG) criteria for MS, reported to the Polish Multiple Sclerosis Registry, were considered for estimation of age- and sex-specific prevalence (per 100,000 persons), and incidence rates (per 100,000 person-years). The demographic data, clinical presentation and treatment strategies also were investigated. RESULTS: On December 31, 2019 in the database were collected data of 329 patients up to 18 years with POMS diagnosis (101 boys and 228 girls; mean age 15.3 ± 3.8 years). The age-adjusted prevalence standardized to the European Standard Population was 5.19/100,000 (95% confidence interval (CI), 4.64-5.78). A significantly higher prevalence was recorded in girls (7.41; 95% CI, 6.48-8.44) than in boys (3.08; 95% CI, 2.50-3.74; P<0.001). The mean annual standardized incidence in Poland between 2015 - 2019 was 0.77 (95%CI, 0.45-1.02) per 100,000 person-years. The highest overall standardized incidence 1.06 (95%CI, 0.82-1.34) was noted in 2018. Most of patients (95.7%) had relapsing-remitting disease with polysymptomatic onset in one-thirds of the cases, and 82.3% were treated with disease-modifying drugs. Family history of MS was reported in 26 cases (7.9%). CONCLUSION: In this first report of registry-based study from Poland an increasing prevalence and incidence of POMS was found during the last years. This temporal trend corroborate the findings of studies conducted elsewhere.

Family-Based Cohort Association Study of PRKCB1, CBLN1 and KCNMB4 Gene Polymorphisms and Autism in Polish Population.

The aim of the study was to perform family-based association analysis of PRKCB1, CBLN1 and KCNMB4 gene polymorphisms and autism disorder. We comprised 206 Caucasian children with autistic spectrum disorder (ASD) and their biological parents. In transmission/disequilibrium test we observed that T-allele of the rs198198 polymorphism of the PRKCB1 gene was more often transmitted to affected children in the male subgroup (p = 0.010). Additionally, the T carrier state was significantly associated with hypotonia (p = 0.048). In the female subgroup, the T-allele carriers more often showed more mobile/vital behavior (p = 0.046). In conclusion, our study showed that the rs198198 of the PRKCB1 gene may be associated with ASD in men and with some features characteristic for the disorder.

Stem Cell Therapies for Cerebral Palsy and Autism Spectrum Disorder-A Systematic Review.

Autism spectrum disorder (ASD) and cerebral palsy (CP) are some of the most common neurodevelopmental diseases. They have multifactorial origin, which means that each case may manifest differently from the others. In patients with ASD, symptoms associated with deficits in social communication and characteristic, repetitive types of behaviors or interests are predominant, while in patients with CP, motor disability is diagnosed with accompanying cognitive impairment of various degrees. In order to minimize their adverse effects, it is necessary to promptly diagnose and incorporate appropriate management, which can significantly improve patient quality of life. One of the therapeutic possibilities is stem cell therapy, already known from other branches of medicine, with high hopes for safe and effective treatment of these diseases. Undoubtedly, in the future we will have to face the challenges that will arise due to the still existing gaps in knowledge and the heterogeneity of this group of patients. The purpose of this systematic review is to summarize briefly the latest achievements and advances in stem cell therapy for ASD and CP.

Eating Behaviors of Children with Autism-Pilot Study, Part II.

Autism spectrum disorder is characterized by social communication deficit and non-normative behavior. The people with autism often experience troubles with feeding. The purpose of this study was to conduct evaluation of the feeding and eating behaviors among children with autism. PATIENTS AND METHODS: The study group included 41 high-functioning autistic children. The control group consisted of 34 children without the ASD. The questionnaire was used to assess the nutritional status. RESULTS: The children with ASD fuss during mealtimes more frequently, they require entertaining and diverting their attention, they are fed by parents, and they consume their meals away from the table. The significant difference found in the use of utensils and food selectivity works to the disadvantage of the Study Group. CONCLUSIONS: The food selectivity occurs significantly more frequently among children with ASD. The feeding and eating problems should be considered on a wider scale. The cooperation of the multidisciplinary and the parents teams should be proposed in the ASD patients care.

Eating Behaviors of Children with Autism-Pilot Study.

Autism Spectrum Disorder (ASD) is the most recognized neuropsychiatric disorder of childhood. Comorbid conditions (such as feeding disorders) are more common among people with autism than among the general population. The most frequent somatic disorders in autistic children include the gastrointestinal disorders observed in 46-91% of patients. The purpose of this study was the evaluation of the nutrition of children with autism, with particular emphasis placed on feeding in the first year of life, in comparison to the group of healthy peers. Participants included 75 Caucasian children (41 children diagnosed with pure autism, and the control group consisting of 34 children without autistic traits). The analysis was performed based on a questionnaire of own design with the first part devoted to the eating practices of the early infancy. Results: Autistic children, as compared to the healthy peers, presented a shortened time of breastfeeding (the children fell asleep at the breast) (p = 0.04), a delayed introduction of dairy products (p = 0.001), the need of more trials to introduce new foods (p = 0.006), a delayed introduction of foods with solid and lumpy structure (p = 0.004), a longer duration of bottle feeding (p = 0.005), delayed attempts to eating using own hands (p = 0.006) and needed a greater support of parents to divert their attention from food during eating (p = 0.05). Conclusions: 1. The dietary problems are more common among children with the autism spectrum disorder than among the population of healthy children, during the first year of life from the time of introducing the complementary foods. 2. The autistic children experience difficulties with eating and require their parents' additional involvement significantly more often than their healthy peers.

The First Metabolome Analysis in Children with Epilepsy and ALG13-CDG Resulting from c.320A>G Variant.

BACKGROUND: ALG13-CDG belongs to the congenital disorders of glycosylation (CDG), which is an expanding group of multisystemic metabolic disorders caused by the N-linked, O-linked oligosaccharides, shared substrates, glycophosphatidylinositol (GPI) anchors, and dolichols pathways with high genetic heterogeneity. Thus, as far as clinical presentation, laboratory findings, and treatment are concerned, many questions are to be answered. Three individuals presented here may serve as a good example of clinical heterogeneity. This manuscript describes the first metabolomic analysis using NMR in three patients with epileptic encephalopathy due to the recurrent c.320A>G variant in ALG13, characterized to date only in about 60 individuals (mostly female). This is an important preliminary step in the understanding of the pathogenesis of the disease associated with this variant in the rare genetic condition. The disease is assumed to be a disorder of N-glycosylation given that this is the only known function of the ALG13 protein. Despite this, protein electrophoresis, which is abnormal in most conditions due to abnormalities in N-glycosylation, has been normal or only mildly abnormal in the ALG13 patients. METHODS: Nuclear magnetic resonance (NMR) spectroscopy in conjunction with multivariate and univariate modelling were used to analyze the metabolic profile of the blood serum samples acquired from the studied patients. RESULTS: Three metabolites were identified as potential biomarkers: betaine, N-acetyl-glycoprotein, and carnitine. CONCLUSIONS: Since presented data are the first to be collected so far, they need be verified in further studies. Our intention was to turn attention toward possible CDG-ALG13 laboratory markers that would have clinical significance.

Dravet Syndrome-The Polish Family's Perspective Study.

AIM: The aim of the paper is to study the prevalence of Dravet Syndrome (DS) in the Polish population and indicate different factors other than seizures reducing the quality of life in such patients. METHOD: A survey was conducted among caregivers of patients with DS by the members of the Polish support group of the Association for People with Severe Refractory Epilepsy DRAVET.PL. It included their experience of the diagnosis, seizures, and treatment-related adverse effects. The caregivers also completed the PedsQL survey, which showed the most important problems. The survey received 55 responses from caregivers of patients with DS (aged 2-25 years). RESULTS: Prior to the diagnosis of DS, 85% of patients presented with status epilepticus lasting more than 30 min, and the frequency of seizures (mostly tonic-clonic or hemiconvulsions) ranged from 2 per week to hundreds per day. After the diagnosis of DS, patients remained on polytherapy (drugs recommended in DS). Before diagnosis, some of them had been on sodium channel blockers. Most patients experienced many adverse effects, including aggression and loss of appetite. The frequency of adverse effects was related to the number of drugs used in this therapy, which had an impact on the results of the PedsQL form, particularly in terms of the physical and social spheres. Intensive care unit stays due to severe status epilepticus also had an influence on the results of the PedsQL form. CONCLUSIONS: Families must be counseled on non-pharmacologic strategies to reduce seizure risk, including avoidance of triggers that commonly induce seizures (including hyperthermia, flashing lights and patterns, sleep abnormalities). In addition to addressing seizures, holistic care for a patient with Dravet syndrome must involve a multidisciplinary team that includes specialists in physical, occupational and speech therapy, neuropsychology, social work.

Nusinersen treatment of Spinal Muscular Atrophy Type 1 - results of expanded access programme in Poland.

AIM OF THE STUDY: This study aimed to evaluate the effects of nusinersen therapy in Polish children with SMA type 1. CLINICAL RATIONALE OF STUDY: Spinal muscular atrophy (SMA) is a neuromuscular disorder that is characterised by the loss of motor neurons, progressive muscle weakness and atrophy, leading to increased disability and mortality. Nusinersen, an antisense oligonucleotide that promotes production of the functional survival motor neuron protein is approved for the treatment of SMA 5q in the European Union. In 2017, an early access programme (EAP) for nusinersen was launched in Poland. In this study, we present the results of nusinersen treatment in Polish patients participating in the EAP. MATERIALS AND METHODS: We collected prospectively clinical data including mutational analysis of SMN1 and SMN2 genes, motor function outcomes as measured on a standardized scales, ventilatory and nutritional status, on SMA type 1 patients receiving nusinersen in three EAP centres in Poland. Scores on the CHOP-INTEND scale after 18-26 months of treatment were compared to baseline. RESULTS: We analysed data from 26 patients with SMA type 1, mean age 4.79 (2-15) years. The mutational analysis revealed two SMN2 gene copies in the majority of patients (61.54%). Three and four copies were found in 34.62% and 3.84%, respectively. Median disease duration was 21 months. Half (n = 13) of the patients required mechanical ventilation at baseline and 57.69% (n = 15) were fed by nasogastric tube or percutaneous endoscopic gastrostomy. No patient worsened during the follow-up. Mean improvement in CHOP-INTEND from baseline to the last follow-up was 7.38 points (p < 0.001). CHOP-INTEND scores did not decline for any patient. Patients with three or more SMN2 gene copies had higher scores than did the patients with two copies (p = 0.013), and they tended to show greater improvement over time, but the difference was not significant (p = 0.324). Shorter disease duration and higher CHOP-INTEND baseline score were associated with a better response (p = 0.015). Patients with a CHOP-INTEND score above the median had higher scores overall than the rest (p < 0.0013), and they improved significantly more than the rest (p = 0.037). Nusinersen was well tolerated, no new safety findings were identified. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our data indicates that nusinersen treatment might be effective in SMA type 1 patients, regardless of their age and functional status.

Neuroimaging of Basal Ganglia in Neurometabolic Diseases in Children.

Diseases primarily affecting the basal ganglia in children result in characteristic disturbances of movement and muscle tone. Both experimental and clinical evidence indicates that the basal ganglia also play a role in higher mental states. The basal ganglia can be affected by neurometabolic, degenerative diseases or other conditions from which they must be differentiated. Neuroradiological findings in basal ganglia diseases are also known. However, they may be similar in different diseases. Their assessment in children may require repeated MRI examinations depending on the stage of brain development (mainly the level of myelination). A large spectrum of pathological changes in the basal ganglia in many diseases is caused by their vulnerability to metabolic abnormalities and chemical or ischemic trauma. The diagnosis is usually established by correlation of clinical and radiological findings. Neuroimaging of basal ganglia in neurometabolic diseases is helpful in early diagnosis and monitoring of changes for optimal therapy. This review focuses on neuroimaging of basal ganglia and its role in the differential diagnosis of inborn errors of metabolism.

Leukoencephalopathy with Calcifications and Cysts-The First Polish Patient with Labrune Syndrome.

Leukoencephalopathy with calcifications and cysts (LCC) is a triad of neuroradiological symptoms characteristic of Labrune syndrome, which was first described in 1996. For 20 years, the diagnosis was only based on clinical, neuroradiological and histopathological findings. Differential diagnosis included a wide spectrum of diseases. Finally, in 2016, genetic mutation in the SNORD118 gene was confirmed to cause Labrune syndrome. The authors describe a case of a teenage girl with progressive headaches, without developmental delay, presenting with calcifications and white matter abnormality in neuroimaging. Follow-up studies showed the progression of leukoencephalopathy and cyst formation. The first symptoms and initial imaging results posed diagnostic challenges. The final diagnosis was established based on genetic results. The authors discuss the possible therapy of LCC with Bevacizumab.

Circadian Profile of Salivary Melatonin Secretion in Hypoxic Ischemic Encephalopathy.

PURPOSE: In the present study, the salivary melatonin secretion in the hypoxic ischemic encephalopathy (HIE) children was measured. The logit model was fitted to the data to obtain the salivary dim light melatonin onsets (DLMOs), and the results were compared with the values estimated from the classic threshold method with a linear interpolation and those previously published for the blood measurements. MATERIALS AND METHODS: 9 patients suffering from HIE aged from 65 to 80 months were included in the study. The melatonin levels were assessed by a radioimmunoassay (RIA). The diurnal melatonin secretion was estimated using a nonlinear least squares method. Student's t-test and the Mann-Whitney U test were used for the comparisons of the obtained parameters. RESULTS: The circadian profiles of the melatonin secretion for both calculation methods do not differ statistically. The DLMO parameters obtained in the blood and saliva samples in children with hypoxic ischemic encephalopathy were similar.

Rambling-trembling analysis of postural control in children aged 3-6 years diagnosed with developmental delay during infancy.

BACKGROUND: Preschool age is fundamental for the development of gross motor skills. Timely detection of postural stability deficits using objective methods would facilitate early implementation of therapeutic strategies. RESEARCH QUESTION: What are the age- and gender-related differences in postural control between preschool children diagnosed with developmental delay in their first year of life and children with typical development? METHODS: The study group consisted of 59 children diagnosed with developmental delay during infancy, who had received physiotherapy in the first year of their life for disorders of postural control and prone locomotion as well as abnormal distribution and magnitude of postural tone. The control group comprised 66 nursery school children with typical development and no history of postural control or movement deficits and no physiotherapy interventions in the first year of their life. The study and control groups were subdivided into four subgroups based on age (3-4 years, 5-6 years) and gender (boys, girls). The data were collected during quiet standing using a force plate. Three 30-second trials were recorded. Stabilographic recordings were analysed using the rambling-trembling approach. RESULTS: Three-way ANOVA revealed a gender effect on all measured variables (p < 0.05). The Tukey HSD (honest significant difference) post-hoc test showed that some of the values of sway range and mean velocity of COP, rambling and trembling in sagittal and frontal plane were significantly greater in control boys aged 3-4 years compared to other subgroups (p < 0.05). SIGNIFICANCE: Long-term postural control monitoring by a pediatrician and/or physiotherapist seems justified and not only in children with a history of infantile developmental delay but also in their healthy peers, especially boys.

NMR-based metabolomics in pediatric drug resistant epilepsy - preliminary results.

Epilepsy in children is the most frequent, heterogeneous and difficult to classify chronic neurologic condition with the etiology found in 35-40% of patients. Our aim is to detect the metabolic differences between the epileptic children and the children with no neurological abnormalities in order to define the metabolic background for therapy monitoring. The studied group included 28 epilepsy patients (median age 12 months) examined with a diagnostic protocol including EEG, videoEEG, 24-hour-EEG, tests for inborn errors of metabolism, chromosomal analysis and molecular study. The reference group consisted of 20 patients (median age 20 months) with no neurological symptoms, no development delay nor chronic diseases. 1H-NMR serum spectra were acquired on 400 MHz spectrometer and analyzed using multivariate and univariate approach with the application of correction for age variation. The epilepsy group was characterized by increased levels of serum N-acetyl-glycoproteins, lactate, creatine, glycine and lipids, whereas the levels of citrate were decreased as compared to the reference group. Choline, lactate, formate and dimethylsulfone were significantly correlated with age. NMR-based metabolomics could provide information on the dynamic metabolic processes in drug-resistant epilepsy yielding not only disease-specific biomarkers but also profound insights into the disease course, treatment effects or drug toxicity.

Evidence for HNRNPH1 being another gene for Bain type syndromic mental retardation.

The HNRNPH2-associated disease (mental retardation, X-linked, syndromic, Bain type [MRXSB, MIM #300986]) is caused by de novo mutations in the X-linked HNRNPH2 gene. MRXSB has been described in six female patients with dysmorphy, developmental delay, intellectual disability, autism, hypotonia and seizures. The reported HNRNPH2 mutations were clustered in the small domain encoding nuclear localization signal; in particular, the p.Arg206Trp was found in four independent de novo events. HNRNPH1 is a conserved autosomal paralogue of HNRNPH2 with a similar function in regulation of pre-mRNAs splicing but so far it has not been associated with human disease. We describe a boy with a disease similar to MRXSB in whom a novel de novo mutation c.616C>T (p.Arg206Trp) in HNRNPH1 was found (ie, the exact paralogue of the recurrent HNRNPH2 mutation). We propose that defective function of HNRNPH2 and HNRNPH1 nuclear localization signal has similar clinical consequences. An important difference between the two diseases is that the HNRNPH1-associated syndrome may occur in boys (as in the case of our proband) which is well explained by the autosomal (chr5q35.3) rather than X-linked localization of the HNRNPH2 gene.