TCEAL1 Loss-of-Function Results in an X-Linked Dominant Neurodevelopmental Syndrome and Drives the Neurological Disease Trait in Xq222 Deletions

An Xq22.2 region upstream of PLP1 has been proposed to underly a neurological disease trait when deleted in 46,XX females. Deletion mapping revealed that heterozygous deletions encompassing the smallest region of overlap (SRO) spanning six Xq22.2 genes (BEX3, RAB40A, TCEAL4, TCEAL3, TCEAL1, and MORF4L2) associate with an early-onset neurological disease trait (EONDT) consisting of hypotonia, intellectual disability, neurobehavioral abnormalities, and dysmorphic facial features. None of the genes within the SRO have been associated with monogenic disease in OMIM. Through local and international collaborations facilitated by GeneMatcher and Matchmaker Exchange, we have identified and herein report seven de novo variants involving TCEAL1 in seven unrelated families: three hemizygous truncating alleles; one hemizygous missense allele; one heterozygous TCEAL1 full gene deletion; one heterozygous contiguous deletion of TCEAL1, TCEAL3, and TCEAL4; and one heterozygous frameshift variant allele. Variants were identified through exome or genome sequencing with trio analysis or through chromosomal microarray. Comparison with previously reported Xq22 deletions encompassing TCEAL1 identified a more-defined syndrome consisting of hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features include strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. An additional maternally inherited hemizygous missense allele of uncertain significance was identified in a male with hypertonia and spasticity without syndromic features. These data provide evidence that TCEAL1 loss of function causes a neurological rare disease trait involving significant neurological impairment with features overlapping the EONDT phenotype in females with the Xq22 deletion

Assessment of the communication difficulties of children and ado lescents with cerebral palsy using Communication Function Classification System

Wstęp: Komunikacja jest jedną z podstawowych potrzeb człowieka. Pozwala na wejście we wspólnotę i utrzymywanie stosunków międzyludzkich. Stanowi sposób przekazywania myśli, uczuć i informacji z zastosowaniem różnorodnych środków, w tym pozawerbalnych. Celem pracy jest ocena funkcjonalna procesu komunikacyjnego dzieci i młodzieży z mózgowym porażeniem dziecięcym z zastosowaniem systemu klasyfikacyjnego Communication Function Classification System (CFCS). Ocenę przeprowadzono różnicując umiejętności komunikacyjne zgodnie z ujęciem zaproponowanym w ICF, to jest z perspektywy aktywności oraz partycypacji. Materiał i metody: Badaniami objęto grupę 210 pacjentów z rozpoznanym mpdz, w wieku do 18 r.ż. Przeprowadzono ocenę funkcjonalną z zastosowaniem systemów klasyfikacyjnych CFCS, GMFCS oraz MACS. Wyniki: Ponad połowa badanych komunikowała się w sposób werbalny. Co czwarty badany nie komunikował się z otoczeniem. Prawie połowa badanych to skuteczni lub wolniejsi, lecz skuteczni nadawcy i odbiorcy dla znanych i nieznanych partnerów (poziom I i II CFCS). Postać zespołu oraz stopień zaburzeń wpływały w sposób istotny na kompetencje komunikacyjne badanych. Wnioski: Poziom kompetencji komunikacyjnych jest zależny od stopnia ciężkości zespołu wyrażonego poprzez poziom GMFCS i MACS.Introduction: Communication is one of the basic human needs. It allows to join a community and maintain interpersonal relations. It is a way of transmitting thoughts, feelings and information using a variety of methods, including non-verbal ones. The aim of the study is the functional assessment of the communication process of children and adolescents with cerebral palsy using the Communication Function Classification System (CFCS). The assessment was carried out by differentiating communication skills in accordance with the approach proposed by the ICF, that is from the perspective of activity and participation. Material and methods: The study group icluded 210 patients with diagnosed cerebral palsy, up to the age of 18 years. A functional assessment was performed using CFCS, GMFCS and MACS classification systems. Results: Over half of the subjects communicated verbally. Every fourth respondent did not communicate with the environment. Almost half of the studied children are effective senders and receivers with unfamiliar and familiar partners (level I and II CFCS). The type of cerebral palsy and the degree of the disability significantly affected the communication competence. Conclusions: Communication abilities level depends on the severity of cerebral palsy expressed by the level of GMFCS and MACS

Eating and drinking ability classification system in cerebral palsy

Czynności jedzenia i picia to złożone procesy, które poza prawidłowym funkcjonowaniem motorycznym obszaru orofacjalnego wymagają również synchronizacji z oddychaniem, stabilności posturalnej, w tym kontroli głowy, oraz szeregu innych sprawności motorycznych. Zaburzenia karmienia są powszechne w mózgowym porażeniu dziecięcym. Istota i ciężkość zaburzeń mogą różnić się, w zależności od deficytów sensomotorycznych, zaburzeń motoryki dużej i małej, czy deficytów poznawczych. Celem pracy jest przedstawienie systemu klasyfikującego ocenę umiejętności jedzenia i picia u osób z mózgowym porażeniem dziecięcym, komplementarnego wobec istniejących systemów służących ocenie lokomocji (GMFCS), manipulacji (MACS) i komunikacji (CFCS).Eating and drinking are complex processes that, in addition to proper motor functioning of orofacial area, require synchronization with breathing, postural stability including head control and a range of other motor skills. Feeding disorder is common in cerebral palsy. The nature and severity of the problems may differ in relation to sensorimotor impairment, gross and fine motor limitations or cognitive deficits. The aim of the study is to present a classification system for assessing the ability of eating and drinking in people with cerebral palsy, complementary to the existing systems assessing gross motor function (GMFCS), manual ability (MACS) and communication function (CFCS)

The Assessment of Eating and Drinking Functions in Infantile Cerebral Palsy for Speech Therapy Treatment

W zespole mózgowego porażenia dziecięcego (mpdz) jednym z częściej występujących objawów są trudności w przyjmowaniu pokarmów i napojów. Czynności jedzenia i picia to złożone procesy, które poza prawidłowym funkcjonowaniem motorycznym obszaru orofacjalnego wymagają również synchronizacji z oddychaniem, stabilności posturalnej, w tym kontroli głowy, oraz szeregu innych sprawności motorycznych. W wyniku mózgowego porażenia dziecięcego funkcjonowanie pacjenta we wszystkich tych obszarach może być zaburzone, co przejawia się trudnościami w jedzeniu i piciu, wpływając na stan odżywienia, a przez to na stan somatyczny i psychiczny pacjenta. Celem pracy jest przedstawienie narzędzia do oceny umiejętności jedzenia i picia u osób z mózgowym porażeniem dziecięcym, komplementarnego wobec systemów służących ocenie lokomocji (GMFCS), manipulacji (MACS) i komunikacji (CFCS), która jest istotnym elementem wielospecjalistycznej diagnozy zaburzeń w zespole dziecięcego porażenia mózgowego na potrzeby postępowania logopedycznego.One of the most frequent symptoms in infantile cerebral palsy syndrome is eating and drinking difficulties. The functions of eating and drinking are complex processes which, apart from the correct motor functioning of the orofacial area, also require synchronization with breathing, postural stability, including controlling of the head, and a number of other motor skills. Because of infantile cerebral palsy, the functioning of the patient in all these areas may be disturbed, which manifests itself in eating and drinking difficulties, influencing the state of nourishment and thereby the patient’s somatic and psychological condition. The goal of the study is to present the tool for the assessment of eating and drinking abilities in cerebral palsy patients, complementary to the systems serving to assess gross motor functions (GMFCS), manual abilities (MACS) and communication (CFCS), which is a significant element in the multi diagnosis of disorders in the cerebral palsy syndrome, necessary for speech therapy treatment

Out-of-hospital cardiac arrest – the late neurological, psychological functions and cerebral change on MRI study: a case series

Cel. Dzieci po pozaszpitalnym nagłym zatrzymaniu krążenia (PsZZK) mogą doświadczać neurologicznych powikłań – od łagodnych zaburzeń poznawczych po ciężkie deficyty psychomotoryczne. Zbadaliśmy odległe następstwa neurologiczne, psychologiczne oraz funkcjonowanie ośrodkowego układu nerwowego (OUN) u dzieci po PsZZK i resuscytacji. Materiał i metody. Przedstawiamy serię 6 przypadków pacjentów (płeć męska, wiek: 9–17 lat), którzy przebyli nagłe zatrzymanie krążenia bez urazu OUN, w okresie obserwacji odległej od 1 do 5 lat (mediana: 2,5 roku). Pacjenci poddani zostali diagnostyce obrazowej głowy w polu elektromagnetycznym z zastosowaniem sekwencji FLAIR (FLAIR MRI). Do oceny neurologicznej oprócz przedmiotowego badania neurologicznego wykorzystano funkcjonalną skalę niezależności (FIM) oraz wskaźnik funkcjonalny „Repty” (RFI). Ocena psychologiczna dokonana została przy użyciu Testu Ravena, Kwestionariusza oceny jakości życia SF-36 oraz Kwestionariusza zdrowotnego dla dzieci i młodzieży KIDSCREEN-52. Wyniki. W badaniu FLAIR MRI obserwowano zmiany pod postacją zaników korowych u 2 spośród 5 pacjentów. W ocenie funkcjonalnej 5 pacjentów uzyskało maksymalną wartość wskaźnika RFI. Trzech badanych uzyskało wyniki poniżej 25. percentyla w skali Ravena (znaczne obniżenie zdolności wnioskowania), jeden pacjent uzyskał wynik powyżej 75. percentyla (wyższy niż przeciętny poziom zdolności wnioskowania). Ocena subiektywnej jakości życia wykazała wysoką ocenę sprawności fizycznej i zadowolenia z życia 5 pacjentów. Jeden badany zgłaszał znacznie obniżoną sprawność fizyczną i obniżony nastrój. Wnioski. W warunkach PsZZK u dzieci gdy pomoc w zakresie BLS udzielona jest szybko i kontynuowane jest postępowanie resusytacyjne oraz leczenie w OIOM, można liczyć na pomyślne rokowanie. Ocena jakości życia wskazuje, że dzieci po NZK zachowały sprawność fizyczną w wysokim stopniu, jednak część badanych deklaruje trudności w nauce i przeciętną samoocenę życiową.Aim. Children who survive out-of-hospital cardiac arrest (OHCA) may suffer neurological consequences, ranging from mild cognitive impairment to severe psychomotor deficits. We investigated the long-term neurological, psychological and central nervous system (CNS) function in children after OHCA and resuscitation. Methods. This is a case series of six patients (all male, aged 9–17 years) after OHCA without CNS injury, with a follow-up of 1 to 5 years (median 2.5 years). Patients were subjected to diagnostic imaging using fluid attenuation inversion recovery magnetic resonance imaging (FLAIR MRI). They also had a routine neurological examination, with additional assessment using the Repty Functional Index (RFI). A psychological assessment with the Raven’s Progressive Matrices (RPM), The Short Form (36) Health Survey (SF-36) and The KIDSCREEN-52 questionnaires were performed. Results. MRI revealed features of cortical atrophy in two of five patients. Five patients obtained a maximal RFI score in most categories in their functional evaluation. Three patients received results below the 25th percentile on the Raven’s scale (i.e., lower level of intelligence), and one patient was above 75th percentile (i.e., high level of intelligence). Quality of life evaluation revealed a high level of physical fitness and life satisfaction in five patients. One patient reported reduced physical ability and a depressed mood. Conclusions. Favourable outcomes in children are expected when basic life support and resuscitation are provided immediately after OHCA, and the treatment is continued in the ICU. This long-term quality of life analysis indicates these children retain their physical ability but may have learning problems and average self-esteem

Correction: Kucińska et al. The Use of CGH Arrays for Identifying Copy Number Variations in Children with Autism Spectrum Disorder. <i>Brain Sci.</i> 2024, <i>14</i>, 273

In the original publication [...

The Use of CGH Arrays for Identifying Copy Number Variations in Children with Autism Spectrum Disorder

Autism spectrum disorders (ASDs) encompass a broad group of neurodevelopmental disorders with varied clinical symptoms, all being characterized by deficits in social communication and repetitive behavior. Although the etiology of ASD is heterogeneous, with many genes involved, a crucial role is believed to be played by copy number variants (CNVs). The present study examines the role of copy number variation in the development of isolated ASD, or ASD with additional clinical features, among a group of 180 patients ranging in age from two years and four months to 17 years and nine months. Samples were taken and subjected to array-based comparative genomic hybridization (aCGH), the gold standard in detecting gains or losses in the genome, using a 4 × 180 CytoSure Autism Research Array, with a resolution of around 75 kb. The results indicated the presence of nine pathogenic and six likely pathogenic imbalances, and 20 variants of uncertain significance (VUSs) among the group. Relevant variants were more prevalent in patients with ASD and additional clinical features. Twelve of the detected variants, four of which were probably pathogenic, would not have been identified using the routine 8 × 60 k microarray. These results confirm the value of microarrays in ASD diagnostics and highlight the need for dedicated tools

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

TCEAL1 loss-of-function results in an X-linked dominant neurodevelopmental syndrome and drives the neurological disease trait in Xq22.2 deletions

An Xq22.2 region upstream of PLP1 has been proposed to underly a neurological disease trait when deleted in 46,XX females. Deletion mapping revealed that heterozygous deletions encompassing the smallest region of overlap (SRO) spanning six Xq22.2 genes (BEX3, RAB40A, TCEAL4, TCEAL3, TCEAL1, and MORF4L2) associate with an early-onset neurological disease trait (EONDT) consisting of hypotonia, intellectual disability, neurobehavioral abnormalities, and dysmorphic facial features. None of the genes within the SRO have been associated with monogenic disease in OMIM. Through local and international collaborations facilitated by GeneMatcher and Matchmaker Exchange, we have identified and herein report seven de novo variants involving TCEAL1 in seven unrelated families: three hemizygous truncating alleles; one hemizygous missense allele; one heterozygous TCEAL1 full gene deletion; one heterozygous contiguous deletion of TCEAL1, TCEAL3, and TCEAL4; and one heterozygous frameshift variant allele. Variants were identified through exome or genome sequencing with trio analysis or through chromosomal microarray. Comparison with previously reported Xq22 deletions encompassing TCEAL1 identified a more-defined syndrome consisting of hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features include strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. An additional maternally inherited hemizygous missense allele of uncertain significance was identified in a male with hypertonia and spasticity without syndromic features. These data provide evidence that TCEAL1 loss of function causes a neurological rare disease trait involving significant neurological impairment with features overlapping the EONDT phenotype in females with the Xq22 deletion