Neuropsychological functioning of adults with PTEN hamartoma tumor syndrome.

PTEN hamartoma tumor syndrome (PHTS) might be associated with a distinct cognitive and psychological profile. However, previous studies are limited, predominantly based on small and pediatric cohorts, likely affected by selection bias, and show a broad range of findings. We aimed to characterize the neuropsychological functioning of adults with PHTS. A total of 40 participants, with intellectual disability as exclusion criterium, completed an extensive clinical neuropsychological assessment including cognitive tasks, questionnaires, and a clinical diagnostic interview. The cognitive tasks and questionnaire data were categorized as below and above average based on 1.5 SD. About 80% of participants showed an average level of intelligence. In addition, 30% and 24% of participants scored below average on immediate memory recall and speed of information processing, respectively. Furthermore, about 25% reported above average scores on the majority of the questionnaires, indicating psychological distress, signs of alexithymia, and cognitive complaints. Personality of participants was characterized by inflexibility, social withdrawal, and difficulties in recognizing and describing their own emotions. Adults with PHTS demonstrate a heterogeneous yet distinct neuropsychological profile that is characterized by slower information processing, psychological problems, and specific personality traits. These findings provide directions on how to optimize the care and daily lives of adults with PHTS.

No relations between executive functions and dimensional models of psychopathology or is time the missing link?

Impaired executive functions (EF) have been found within various mental disorders (e.g., attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia spectrum disorders) as described in DSM-5. However, although impaired EF has been observed within several categories of mental disorders, empirical research on direct relations between EF and broader dimension of psychopathology is still scarce. Therefore, in the current investigation we examined relations between three EF performance tasks and self-reported dimensions of psychopathology (i.e., the internalizing, externalizing, and thought disorder spectra) in a combined dataset of patients with a broad range of mental disorders (N = 440). Despite previously reported results that indicate impaired EF in several categories of mental disorders, in this study no direct relations were found between EF performance tasks and self-reported broader dimensions of psychopathology. These results indicate that relations between EF and psychopathology could be more complex and non-linear in nature. We evaluate the need for integration of EF and dimensional models of psychopathology and reflect on EF as a possible transdiagnostic factor of psychopathology.

The Relationship Between Cognitive and Behavioral Measures of Executive Function in the Context of Elementary School

Cognitive and behavioral measures are used to assess executive functions. Previous research shows that these measures tap different underlying aspects. However, much less is known about this relationship, when assessed in the context of elementary education. The current study aims to contribute to this body of research by examining the relationship between cognitive and behavioral measures (rated by parents and teachers) of executive functioning in an elementary school context, using two study designs. In study 1, the relationship between behavioral measures (using the Behaviour Rating Inventory of Executive Function: BRIEF) and cognitive measures was examined in terms of inhibitory control, planning and organization abilities as well as processing speed using a sample of 51 children (8-10 years old). In study 2, the relationship between behavioral measures and cognitive measures of inhibitory control, cognitive flexibility, and working memory was studied in a sample of 27 children (8-10 years old). Spearman’s rho coefficients were calculated between the BRIEF and neuropsychological tasks measuring the aforementioned cognitive functions. Only processing speed appeared to be positively related to parent- and teacher- rated executive function problems: lower speed of information processing was associated with more executive function problems in daily life. No other correlation between cognitive and behavioral measures of executive functioning was statistically significant. These findings in the elementary school context confirm that cognitive and behavioral measures reflect different but complementary aspects of executive functioning. Furthermore, they suggest that behavior ratings of executive functioning might reflect general problems, such as slower speed of information processing. (AU)

Hypertension with hidden causes: the cognitive and behavioral profile of an adult female with chronic stress and 16p11.2 microdeletion.

This case report aims to alert physicians to neuropsychological features and chromosomal variants that may underly resistant hypertension. We present a 35-year-old female patient with hypertensive crisis (BP 260/160 mmHg), initially treated with a combination of calcium antagonists, beta blockers, diuretics and angiotensin-converting enzyme (ACE)-inhibitors, though with little improvement. Cushing's syndrome, Conn's syndrome, and glucocorticoid receptor deficiency were ruled out. Multidisciplinary examination of medical history and (hetero)anamneses including psychosocial factors revealed mild dysmorphic body features, developmental delay, early diagnosis of autism spectrum disorder, a history of being bullied at school, little peer contact, learning disabilities, and special education. Neuropsychological assessment demonstrated below average to low average intelligence quotient, cognitive impairments, and psychopathology. Parallel genetic analyses revealed a rare 16p11.2 microdeletion syndrome. These concurrent examinations explained the patient's life-long high stress levels. After psychological treatment, with additional support at home, her blood pressure lowered to normal levels and antihypertensive drugs were no longer needed.

Measuring Adaptive Behavior in Patients with Mendelian Neurodevelopmental Disorders. Comparison of ABAS-3 and Dutch Vineland Scales.

Objective: Several instruments are available for measuring (aspects of) adaptive functioning, but knowledge is lacking about which is best to use to monitor patients with etiologically homogeneous neurodevelopmental disorders. In this study we compare the use of the Vineland-Z and ABAS-3 adaptive behavior scales in such a specific group. Method: Of patients with a molecularly confirmed diagnosis of Kleefstra syndrome, 34 were assessed with both the Vineland-Z and ABAS-3 of which 12 (35,3%) males and 22 (64,7%) females. Raw scores and developmental ages were calculated and a comparison between the instruments was done via correlation analysis. Results: Biological age ranged from 12 to 50 years old (median age of 23,1 ± 9,6 years). Pearson r correlation analyses show that the Vineland-Z and ABAS-3 assessments are highly interchangeable in this population. However, there are practical issues which require attention: (i) the use of ABAS-3 needs several versions to cover the whole adaptive spectrum, and (ii) the Vineland-Z discriminates more at the lower end of the adaptive functioning spectrum compared to the ABAS-3, but less at the higher end. An ideal instrument for this specific purpose is not yet available. Conclusions: We recommend that either the Vineland-Z, with modification of the dated items, the abridged version of the Vineland III, or a merge of the 0-4/517 ABAS-3 versions would work best to assess the entire spectrum of adaptive functioning adequately.

Neurocognitive Recovery in Abstinent Patients with Alcohol Use Disorder: A Scoping Review for Associated Factors.

Objective: Studies have reported inconsistent results regarding the extent to which neurocognitive recovery occurs in abstinent patients with alcohol use disorder (AUD). In addition to abstinence, other factors may have influenced this process and contributed to the inconsistencies. This review examines the factors investigated in this regard and describes the possible influence of each factor based on the evidence collected. Methodology: PubMed was systematically searched for articles published between January 2000 and July 2023. Longitudinal humane studies investigating neurocognitive recovery in abstinent adult AUD patients were included. Studies with a cross-sectional design were excluded, as were studies that did not classify AUD according to the DSM-IV or 5 criteria, only examined binge use, did not report neuropsychological outcomes or duration of abstinence, or where neurological disorders were present. Results: Sixteen categories of factors were distinguished from 31 full-text articles. Consistent patterns were found, indicating an association between neurocognitive recovery and the "smoking" and 'brain volume" factors. Consistent patterns were also found indicating that there is no relationship with "quantities of alcohol used" and "education level." A similar consistent pattern was also found for "polysubstance use", "gender" and "verbal reading", but the number of studies is considered limited. The association with "age" is studied frequently but with inconsistent findings. The remaining eight factors were regarded as understudied. Conclusion: The clearest patterns emerging from the evidence are a predominantly negative influence of smoking on neurocognitive recovery, associations between changes in brain area volume and neurocognitive recovery, and no association between neurocognitive recovery and the amount of alcohol consumed, as measured by self-report, nor with educational attainment. Future research on the understudied factors and factors with inconsistent evidence is needed, preferably through longitudinal designs with multiple assessment periods starting after at least two weeks of abstinence.

Impaired Executive Functioning Associated with Alcohol-Related Neurocognitive Disorder including Korsakoff's Syndrome.

(1) Background: chronic alcohol use is consistently associated with impaired executive functioning, but its profile across the spectrum from mild to major alcohol-related cognitive impairment is, to date, unclear. This study aims to compare executive performances of patients with alcohol-induced neurocognitive disorder, including Korsakoff's syndrome (KS), by using a computerized assessment battery allowing a fine-grained and precise neuropsychological assessment; (2) Methods: performances of 22 patients with alcohol-related cognitive impairment (ARCI) and 20 patients with KS were compared to those of 22 matched non-alcoholic controls. All participants were diagnosed in accordance with DSM-5-TR criteria and were at least six weeks abstinent from alcohol prior to assessment. Executive function was evaluated using four subtests of Cambridge Neuropsychological Test Automated Battery (CANTAB®); (3) Results: significant differences between groups were found on spatial working memory (updating), sustained attention and inhibitory control, set shifting, and planning. Healthy controls performed significantly better than both patient groups (Games-Howell post hoc; p < 0.05), but no differences in performance were found between the ARCI and KS group; (4) Conclusions: ARCI and KS patients showed significant executive impairments, most prominent in updating, set-shifting and general planning abilities. Findings suggest equivalent levels of executive function in ARCI and KS patients. Our results highlight executive function as a significant hallmark of alcohol-induced neurocognitive disorder and stipulate the importance of early assessment and evaluation of skills to guide treatment.

Forensically relevant challenging behaviors and the genetics domain.

Impulsive and aggressive behaviors along with intellectual disabilities often manifest in the context of genetic disorders and are a persisting challenge to professionals in the forensic psychiatric and psychological setting. The following chapter comprises an overview of relevant factors in the gene-context-behavior interaction such as monoamine oxidase A activity and specific epileptic phenomena. It presents several examples of monogenetic disorders with behaviors from the aggression spectrum and summarizes emerging strategies for treatment and clinical management thereof. The final part focuses on challenges and future developments in this field with relevance for the judicial and forensic systems. It is concluded that the relationship between a genetic syndrome and forensically relevant and/or violent behaviors should typically be addressed within a multidisciplinary framework that also includes the application of modern genetic techniques.

A time-series perspective on executive functioning: The benefits of a dynamic approach to random number generation.

OBJECTIVES: Executive functioning (EF) is a key topic in neuropsychology. A multitude of underlying processes and constructs have been suggested to explain EF, which are measured by at least as many different neuropsychological tests. However, these tests often refer to summary statistics to quantify the construct under study, failing to capture the dynamic nature of EF. An alternative to these summary statistics is a time-series approach that quantifies all the available temporal information. METHODS: We used recurrence quantification analysis (RQA) to quantify the characteristics of any temporal pattern in random number generation data and we compared RQA to the traditional and static analysis of random number sequences. RESULTS: The traditional measures yield inconsistent results with increasing sequences length, both for computer-generated and human-generated sequences, whereas the RQA measures do not. CONCLUSION: The results suggest that a time-series approach does a better job at modelling what is happening on different time-scales, and, therefore, is better at explaining how EF is changing in the course of the random number generation task. We argue that it is likely that these findings also apply to other neuropsychological EF tests, and that a time-series approach is an important addition to the study of EF.

The structure of dimensions of psychopathology in normative and clinical samples: Applying causal discovery to MMPI-2-RF scales to investigate clustering of psychopathology spectra and p-factors.

We applied a Bayesian Constraint-based Causal Discovery method (BCCD) to examine the hierarchical structure of the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) Restructured Clinical (RC) scales. Two different general psychopathology super spectra (p-factor) scales were extracted from (1) all RC scales and (2) all RC scales except the RCd (Demoralization) scale. These p-factor scales were included in separate models to investigate the structure of dimensions of psychopathology in a normative (n = 3,242) and clinical (n = 2,466) sample, as well as the combined normative/clinical sample (N = 5,708), by applying the BCCD algorithm to obtain a data-driven reconstruction of the internal hierarchical structure of the MMPI-2-RF. Research on the underlying structure of the MMPI-2-RF has clinical relevance as well as conceptual relevance in the context of the HiTOP model. Results demonstrated that the syndromes measured with the RC-scales-in presence of a p-factor-cluster into six spectra: internalizing, disinhibited-externalizing, antagonistic-externalizing, thought disorder, detachment, and somatoform. These results may support a super spectrum construct, as it was necessary for obtaining a bottom-up reconstruction of this six-spectrum structure. We found support for superiority of a broad super spectrum with additional variance over and above demoralization, as it resulted in the clearest structure (i.e., clustering of the RC scales). Furthermore, our results indicate independent support for the bifactor structure model of psychopathology.

An Exploratory Study of MMPI-2-RF Personality and Psychopathology Profiles of Adults with Autism Spectrum Disorder without Intellectual Disability.

Objective: More empirical research is needed to disentangle the phenotypes of autism spectrum disorder (ASD) and cluster C personality symptomatology (CCPD), as both show similarities in their clinical presentation. We explored personality and psychopathology dimensions as conceptualized in contemporary dimensional taxonomies (i.e., hierarchical taxonomy of psychopathology; HiTOP) in adults with ASD without intellectual disability operationalized by the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF). Method: Applying secondary analytic processes using clinical data, we cross-examined the MMPI-2-RF profiles of adults with ASD (n = 28) compared to adults with Cluster C personality disorders (CCPD; n = 28) and a control group (n = 28) by conducting nonparametric tests and assessing effect sizes. Results: The profiles of the ASD and CCPD groups evidenced to be similar, and both average clinical profiles diverged from the average control group profiles by elevated levels of demoralization, internalizing, and somatization symptomatology. There were small differences between the average profiles of adults with ASD and adults with CCPD. Additional research using dimensional measures of psychopathology could elucidate the dimensional phenotypes of ASD and CCPD. Conclusions: Based on the results in this study, the MMPI-2-RF may not meaningfully discriminate between the two clinical presentations, with the exception of various externalizing scales.

Cognitive Phenotype and Psychopathology in Noonan Syndrome Spectrum Disorders through Various Ras/MAPK Pathway Associated Gene Variants.

Cognitive difficulties are argued to be common in patients with Noonan syndrome spectrum disorders (NSSDs), but findings are based on studies in which patients with variants in PTPN11 (prevalence ~50%) were overrepresented. The current study, using a structured clinical approach, describes the cognitive phenotype and psychopathology of 100 patients (aged 6 to 61 years) with nine different gene variants in the Ras/MAPK pathway underlying NSSDs (PTPN11n = 61, PTPN11 Noonan syndrome with multiple lentigines n = 3, SOS1n = 14, KRASn = 7, LZTR1n = 5, RAF1n = 4, SHOC2n = 2, CBLn = 2, SOS2n = 2). After weighted assessment and bootstrapping of the results of individual neuropsychological assessments and measures of psychopathology, cognitive performances in most variant groups were within the ranges of expectation. IQs were significantly lower in patients with variants in PTPN11, KRAS, RAF1, and SHOC2, but no specific cognitive impairments were found. The performances of younger participants (<16 years of age) did not differ from those of adults. Alexithymia and internalizing problems were more frequent in patients with variants in PTPN11 and SOS1, while PTPN11 patients also showed higher levels of externalizing problems. These results stress the need to take intelligence into account when interpreting lower cognitive performances in individual neuropsychological assessments, which is crucial for an adequate understanding and guidance of patients with NSSDs.

A Patient with Moderate Intellectual Disability and 49, XXXYY Karyotype.

Klinefelter syndrome is a chromosomal disorder in which one extra X chromosome is present (47,XXY). Several other numeric variants of this syndrome are described that comprise one or more additional sex chromosomes such as 48,XXXY, 48,XXYY and 49,XXXXY. These rare conditions are often associated with increased risk for congenital malformations, additional medical problems, and a more complex psychological phenotype. Since 1963, apart from two infants, only four adult patients with a XXXYY pentasomy have been published as case report. The present paper critically reviews the existing literature and provides detailed assessments of a 25-year-old male with intellectual disability and autism. For the first time, this very rare pentasomy is now recorded using all information about developmental history as well as findings from genetic, somatic, endocrinological and neuropsychological examination. It is concluded that children born with abnormalities of the external genitalia should always be evaluated for genetic abnormalities in order to avoid unwanted delay of appropriately designed multidisciplinary medical and psychological treatment.

Reviewing the availability, efficacy and clinical utility of Telepsychology in dialectical behavior therapy (Tele-DBT).

BACKGROUND: Telepsychology is increasingly being implemented in mental health care. We conducted a scoping review on the best available research evidence regarding availability, efficacy and clinical utility of telepsychology in DBT. The review was performed using PRISMA-ScR guidelines. Our aim was to help DBT-therapists make empirically supported decisions about the use of telepsychology during and after the current pandemic and to anticipate the changing digital needs of patients and clinicians. METHODS: A search was conducted in PubMed, Embase, PsycARTICLES and Web of Science. Search terms for telepsychology were included and combined with search terms that relate to DBT. RESULTS: Our search and selection procedures resulted in 41 articles containing information on phone consultation, smartphone applications, internet delivered skills training, videoconferencing, virtual reality and computer- or video-assisted interventions in DBT. CONCLUSIONS: The majority of research about telepsychology in DBT has focused on the treatment mode of between-session contact. However, more trials using sophisticated empirical methodologies are needed. Quantitative data on the efficacy and utility of online and blended alternatives to standard (i.e. face-to-face) individual therapy, skills training and therapist consultation team were scarce. The studies that we found were designed to evaluate feasibility and usability. A permanent shift to videoconferencing or online training is therefore not warranted as long as face-to-face is an option. In all, there is an urgent need to compare standard DBT to online or blended DBT. Smartphone apps and virtual reality (VR) are experienced as an acceptable facilitator in access and implantation of DBT skills. In addition, we have to move forward on telepsychology applications by consulting our patients, younger peers and experts in adjacent fields if we want DBT to remain effective and relevant in the digital age.

Speech-language profiles in the context of cognitive and adaptive functioning in SATB2-associated syndrome.

SATB2-associated syndrome (SAS) is a neurodevelopmental disorder caused by heterozygous pathogenic variants in the SATB2 gene, and is typically characterized by intellectual disability and severely impaired communication skills. The goal of this study was to contribute to the understanding of speech and language impairments in SAS, in the context of general developmental skills and cognitive and adaptive functioning. We performed detailed oral motor, speech and language profiling in combination with neuropsychological assessments in 23 individuals with a molecularly confirmed SAS diagnosis: 11 primarily verbal individuals and 12 primarily nonverbal individuals, independent of their ages. All individuals had severe receptive language delays. For all verbal individuals, we were able to define underlying speech conditions. While childhood apraxia of speech was most prevalent, oral motor problems appeared frequent as well and were more present in the nonverbal group than in the verbal group. For seven individuals, age-appropriate Wechsler indices could be derived, showing that the level of intellectual functioning of these individuals varied from moderate-mild ID to mild ID-borderline intellectual functioning. Assessments of adaptive functioning with the Vineland Screener showed relatively high scores on the domain "daily functioning" and relatively low scores on the domain "communication" in most individuals. Altogether, this study provides a detailed delineation of oral motor, speech and language skills and neuropsychological functioning in individuals with SAS, and can provide families and caregivers with information to guide diagnosis, management and treatment approaches.

RandseqR: An R Package for Describing Performance on the Random Number Generation Task.

The Random Number Generation (RNG) task has a long history in neuropsychology as an assessment procedure for executive functioning. In recent years, understanding of human (executive) behavior has gradually changed from reflecting a static to a dynamic process and this shift in thinking about behavior gives a new angle to interpret test results. However, this shift also asks for different methods to process random number sequences. The RNG task is suited for applying non-linear methods needed to uncover the underlying dynamics of random number generation. In the current article we present RandseqR: an R-package that combines the calculation of classic randomization measures and Recurrence Quantification Analysis. RandseqR is an easy to use, flexible and fast way to process random number sequences and readies the RNG task for current scientific and clinical use.

Inhibitory Control and Craving in Dual Disorders and Recurrent Substance Use. Preliminary Findings.

Objective: In Dual Disorders (DD), which involves the co-occurrence of a disorder in substance use and a mental disorder, recurrent struggles with addictive behavior are frequent. Neuropsychological knowledge concerning the profile of inhibitory control and the irresistible urge to use substances (craving) within the DD patient group may contribute to the prevention of this recurrent addictive behavior. Methods: Inhibitory control and craving were assessed in 25 patients with DD and 25 healthy controls (HC). Inhibitory control tasks (Go/No-go task and Stop Signal Task) were performed combined with brain measurements (Event Related Potentials) mapping inhibitory control. Moreover, implicit and explicit measures concerning craving were administered. Statistical DD and HC comparisons, correlational and regression analyses on exploratory base were conducted. Results: DD patients committed more inhibitory control errors than HC when confronted with (alcohol) consumption-related picture stimuli. Furthermore, patients with DD showed higher levels of implicit and explicit craving. The number of inhibitory control errors was positively related to levels of implicit and explicit craving. Moreover, explicit craving and impulsivity (as a dimension of inhibitory control) predicted the severity of addictive behavior. Event Related Potential analyses did not show differences in inhibitory control-associated brain activity between DD patients and HC; both groups showed reduction of P300 amplitudes in response to alcohol pictures. Conclusions: Impulsivity and craving are elevated in DD patients and show predictive value for the severity of addictive behavior. One's level of impulsive action tendency may trigger less effort to control (recurrent) substance use. The findings may contribute to existing DD treatment indications by the promotion of impulse control training via "stop-think-act" methods for DD patients.

Robustness of the Maladaptive Personality Plaster: An Investigation of Stability of the PSY-5-r in Adults over 20 Years.

The long-term stability of maladaptive personality traits in the general population has been under-investigated. The current study examined the longitudinal 20-year mean-level stability and rank-order consistency of five maladaptive personality traits-as measured with the Personality Psychopathology-5-r scales. Correlations and regression analysis were conducted to test both types of stability comparing raw scores of scale administrations in a general population sample in both 1992 and 2012 (N = 65). Repeated measures analysis of variance demonstrated significant mean-level stability of the PSY-5-r traits over 20 years. The PSY-5-r scales demonstrated significant rank-order consistency as evidenced by correlational analyses and reliability coefficients. The scales Aggressiveness-r (r = .73), Neuroticism/Negative Emotionality-r (r = .65), Introversion/Low Positive Emotionality-r (r = .63), and Disconstraint-r (r = .56), evidenced strong rank-order stability, whereas Psychoticism-r (r = .3) showed moderate rank-order consistency. The results of the present study indicate that maladaptive personality traits as measured with the PSY-5-r scales are relatively stable over 20 years in an adult community population.

Adult male patient with severe intellectual disability caused by a homozygous mutation in the HNMT gene.

Histamine is involved in various physiological functions like sleep-wake cycle and stress regulation. The histamine N-methyltransferase (HNMT) enzyme is the only pathway for termination of histamine neurotransmission in the central nervous system. Experiments with HNMT knockout mice generated aggressive behaviours and dysregulation of sleep-wake cycles. Recently, seven members of two unrelated consanguineous families have been reported in whom two different missense HNMT mutations were identified. All showed severe intellectual disability, delayed speech development and mild regression from the age of 5 years without, however, any dysmorphisms or congenital abnormality. A diagnosis of mental retardation, autosomal recessive 51 was made. Here, we describe a severely mentally retarded adolescent male born from second cousins with a homozygous mutation in HNMT. His phenotypic profile comprised aggression, delayed speech, autism, sleep disturbances and gastro-intestinal problems. At early age, regression occurred. Treatment with hydroxyzine combined with a histamine-restricted diet resulted in significant general improvement.

A de novo CTNNB1 Novel Splice Variant in an Adult Female with Severe Intellectual Disability.

The catenin beta-1 (CTNNB1) gene, encoding a sub-unit of the cadherin/catenin protein complex that is involved in the Wnt signalling pathway important for proper interneuron development, is considered to be causative for the rare autosomal dominant mental retardation syndrome, formerly called MRD19 but later renamed neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV). Its main characteristics are moderate to severe intellectual disability (ID), disruptive autistic behaviours, microcephaly, absent or limited speech, facial dysmorphisms, peripheral hypertonia/spasticity, motor delay and visual defects. So far, 35 patients have been reported with a de novo loss-of-function variant in CTNNB1. In two other patients, a deletion comprising the full gene was found. Four out of the 37 patients were of adult age (range: 27-51 years), while the majority was infant or adolescent (range: 0-20 years). Here, a 32-year-old severely intellectually disabled female patient is described in whom exome sequencing disclosed a de novo heterozygous splice site variant in the CTNNB1 gene [Chr3(GRCh37): g.41267064G>T; NM_001904.3: 23. c.734+1G>T; r. spl?]. Somatic investigation disclosed significant microcephaly and minor facial dysmorphisms. Neurological examination demonstrated severe kyphoscoliosis, distal spastic tetraparesis, especially of the legs with increased tendon reflexes and bilateral Babinski sign, resulting in severely impaired walking capability with a broad-based gait. Apart from strabismus, no ophthalmological abnormalities were found. Here, the reported variant in the CTNNB1 gene was not published earlier nor is included in the international databases. This specific variant is considered to be causative for the severe ID, autism and the somato-neurological phenotype of the patient and corresponds with a diagnosis of NEDSDV.