The phenotype of Sotos syndrome in adulthood: A review of 44 individuals.

Sotos syndrome is an overgrowth-intellectual disability (OGID) syndrome caused by NSD1 pathogenic variants and characterized by a distinctive facial appearance, an intellectual disability, tall stature and/or macrocephaly. Other associated clinical features include scoliosis, seizures, renal anomalies, and cardiac anomalies. However, many of the published Sotos syndrome clinical descriptions are based on studies of children; the phenotype in adults with Sotos syndrome is not yet well described. Given that it is now 17 years since disruption of NSD1 was shown to cause Sotos syndrome, many of the children first reported are now adults. It is therefore timely to investigate the phenotype of 44 adults with Sotos syndrome and NSD1 pathogenic variants. We have shown that adults with Sotos syndrome display a wide spectrum of intellectual ability with functioning ranging from fully independent to fully dependent. Reproductive rates are low. In our cohort, median height in adult women is +1.9 SD and men +0.5 SD. There is a distinctive facial appearance in adults with a tall, square, prominent chin. Reassuringly, adults with Sotos syndrome are generally healthy with few new medical issues; however, lymphedema, poor dentition, hearing loss, contractures and tremor have developed in a small number of individuals.

The behavioral characteristics of Sotos syndrome.

In this study we describe the levels of clinically significant behavior in participants with Sotos syndrome relative to three matched contrast groups in which the behavioral phenotype is well documented (Autism Spectrum Disorder, ASD; Prader-Willi, and Down syndromes). Parents and carers of 38 individuals with Sotos syndrome (mean age = 17.3; SD = 9.36), completed questionnaires regarding self-injury, aggression, repetitive behavior, autism spectrum phenomenology, overactivity, impulsivity and mood, interest and pleasure. Individuals with Sotos syndrome showed an increased risk of self-injurious behavior, physical aggression, and destruction of property relative to the Down syndrome group but not a greater risk of stereotyped behavior. Impulsivity and levels of activity were also significantly higher relative to those with Down syndrome and comparable to those with ASD. A large proportion of participants met the cut off score for ASD (70.3%) and Autism (32.4%) on the Social Communication Questionnaire. Social impairments were particularly prominent with repetitive behavior and communication impairments less characteristic of the syndrome. Interestingly, preference for routine and repetitive language were heightened in individuals with Sotos syndrome and the repetitive behavior profile was strikingly similar to that observed in individuals with Prader-Willi syndrome. These findings build upon previous research and provide further evidence of the behavioral phenotype associated with Sotos syndrome.

Sensory processing in Sotos syndrome and Tatton-Brown-Rahman Syndrome.

Sotos syndrome (Sotos) and Tatton-Brown-Rahman Syndrome (TBRS) are two of the most common overgrowth disorders associated with intellectual disability. Individuals with these syndromes tend to have similar cognitive profiles and high likelihood of autism symptomatology. However, whether and how sensory processing is affected is currently unknown. Parents/caregivers of 36 children with Sotos and 20 children with TBRS completed the Child Sensory Profile-2 (CSP-2) and the Sensory Behavior Questionnaire (SBQ) along with other standardized questionnaires assessing autistic traits (Social Responsiveness Scale, Second Edition, SRS-2), attention deficit hyperactivity disorder (ADHD) traits (Conners 3), anxiety (Spence Children's Anxiety Scale, Parent Version, SCAS-P), and adaptive behavior (Vineland Adaptive Behavior Scales Third Edition). Sensory processing differences were clearly evident in both syndromes, though there was significant variation in both cohorts. SBQ data indicated that both the frequency and impact of sensory behavior were more severe when compared to neurotypicals, with levels of sensory behavior impact and frequency being similar to autistic children. CSP-2 data indicated 77% of children with Sotos and 85% children with TBRS displayed clear differences in sensory Registration (missing sensory input). Clear differences relating to Body Position (proprioceptive response to joint and muscle position; 79% Sotos; 90% TBRS) and Touch (somatosensory response to touch on skin; 56% Sotos; 60% TBRS) were also particularly prevalent. Correlation analyses demonstrated that in both syndromes sensory processing differences tend to be associated with difficulties relating to autistic traits, anxiety, and some domains of ADHD. In Sotos, sensory processing differences were also associated with lower adaptive behavior skills. This first detailed assessment of sensory processing, alongside other clinical features, in relatively large cohorts of children with Sotos and TBRS, demonstrates that sensory processing differences have a profound impact on everyday life. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Disrupted epigenetics in the Sotos syndrome neurobehavioral phenotype.

PURPOSE OF REVIEW: Sotos syndrome is among a growing list of disorders resulting from mutations in epigenetic machinery genes. These Mendelian disorders of the epigenetic machinery (MDEMs) exhibit phenotypic overlap broadly characterized by intellectual disability and atypical growth and behaviors. Manifestations of Sotos syndrome include a distinct facial appearance, overgrowth, intellectual disability, and behavioral issues. Herein we review key aspects of Sotos syndrome, focusing on the neurobehavioral phenotype. Additionally, we highlight recent advances in our understanding of molecular pathogenesis implicating epigenetic mechanisms. RECENT FINDINGS: Increasing evidence suggests MDEMs account for ∼19% of intellectual disability and ∼45% of overgrowth combined with intellectual disability, with Sotos syndrome constituting most of the latter. Although the genetic cause of Sotos syndrome, disruption of the histone methyltransferase writer NSD1, is well established, recent studies have further delineated the neurobehavioral phenotype and provided insight into disease pathogenesis. Explicitly, NSD1 target genes accounting for a subset of Sotos syndrome features and a specific DNA methylation signature have been identified. SUMMARY: Sotos syndrome is, therefore, a genetic disorder with epigenetic consequences. Its characteristic neurobehavioral phenotype and those of related MDEMs illustrate the essential role epigenetic mechanisms play in neurologic development. Improvement in our understanding of molecular pathogenesis has important implications for development of diagnostic tests and therapeutic interventions.

The cognitive profile of Sotos syndrome.

Sotos syndrome is a congenital overgrowth disorder, associated with intellectual disability. Previous research suggests that Sotos syndrome may be associated with relative strength in verbal ability and relative weakness in non-verbal reasoning ability but this has not been explicitly assessed. To date, the cognitive profile of Sotos syndrome is unknown. Cognitive abilities of a large and representative sample of individuals with Sotos syndrome (N = 52) were assessed using the British Ability Scales (BAS3). The majority of participants had intellectual disability or borderline intellectual functioning. The cluster score profile analysis revealed a consistent verbal ability > non-verbal reasoning ability profile. Four specific criteria were proposed as the Sotos syndrome cognitive profile (SSCP): verbal ability > non-verbal reasoning ability; quantitative reasoning T-score or matrices T-score <20th percentile; quantitative reasoning T-score < mean T-score; recognition of designs T-score or recognition of pictures T-score > mean T-score. Of the 35 participants included in the profile analysis, 28 met all four SSCP criteria, yielding a sensitivity of 0.8. The sensitivity of each of the SSCP criteria was >0.9. Individuals with Sotos syndrome display a clear and consistent cognitive profile, characterized by relative strength in verbal ability and visuospatial memory but relative weakness in non-verbal reasoning ability and quantitative reasoning. This has important implications for the education of individuals with Sotos syndrome.

Parent-Reported Communication Abilities of Children with Sotos Syndrome: Evidence from the Children's Communication Checklist-2.

Sotos syndrome is a congenital overgrowth syndrome associated with intellectual disability. This study investigated communicative abilities of children with Sotos syndrome (n = 31), using the Children's Communication Checklist, second edition. A cross-syndrome approach was used to establish the specificity of these abilities. Children with Williams syndrome (n = 34) were used as a comparison group. In both groups, the majority of participants had communicative impairment. Children with Sotos syndrome had an uneven pragmatic language profile and greater impairment with social relations, compared with restricted interests. Overall, children with Sotos syndrome had difficulties with both language structure and pragmatic language and a specific profile of relative difficulty with using nonverbal communication, using context-appropriate language and understanding peer relationships.

Characteristics of Autism Spectrum Disorder in Sotos Syndrome.

Sotos syndrome is a congenital overgrowth disorder with an incidence of approximately 1 in 14,000. This study investigated behavioural characteristics of ASD within a large cohort of individuals with Sotos syndrome (n = 78). As measured by the Social Responsiveness Scale, second edition (SRS-2), 65 participants (83.33 %) met clinical cut-off (T-score ≥60). There was no significant gender difference in symptom severity. There was a significant effect of age, with lower scores observed in early childhood and adulthood, compared to childhood. Furthermore, individuals with Sotos syndrome appear to display a trait profile that is similar to that identified in ASD. Overall, these findings indicate that the majority of individuals with Sotos syndrome display clinically significant behavioural symptomatology associated with ASD.

Neuropsiquiatría en el Síndrome de Sotos: revisión y actualización a propósito de un caso / Neuropshychiatry in Sotos' Syndrome: A Systematic Update And A Case Report

El Síndrome de Sotos o gigantismo cerebral es un síndrome de sobrecrecimiento acelerado durante la infancia, con un aspecto facial característico y dificultades de aprendizaje. Incluye alteraciones conductuales y clínica neuropsiquiátrica como déficits de atención, inhibición social, retraso y torpeza psicomotoras, impulsividad y agresividad. Describimos el caso de un varón de 9 años con Síndrome de Sotos que presentaba conductas oposicionistas, impulsividad y agresividad

Sotos syndrome or cerebral gigantism is a syndrome of accelerated overgrowth during childhood with characteristic facial features and learning disabilities. It includes behavioral disorders and neuropsychiatric signs such as attention deficits, social inhibition, psychomotor delay and clumsiness, tantrums and aggressiveness. We describe a case of 9 years old male individual with Sotos syndrome who exhibits oppositional behaviour, impulsiveness and aggressiveness