Relationship between serum cortisol levels, stereotypies, and the presence of autism spectrum disorder in patients with severe intellectual disability.

Stereotypies are one of the diagnostic criteria for autism spectrum disorder (ASD) and are common to both ASD and intellectual disability (ID). Previous studies have been inconclusive, with some showing a positive correlation between stereotypies and cortisol, while others have shown a negative correlation. We hypothesised and investigated the presence of ASD as one of the variables involved in this discrepancy. We tested the following hypotheses on serum cortisol in a total of 84 hospitalised patients with severe ID and ASD with severe ID. Hypothesis (1) Higher levels of stereotypies are associated with higher levels of serum cortisol. Hypothesis (2) The presence of ASD will moderate the association between stereotypies and high serum cortisol levels. The results of the analysis supported hypotheses (1) and (2). We also found that in the population with ID, serum cortisol levels were significantly lower in the ASD group compared to the non-ASD group. The present findings that the association between stereotypies and serum cortisol levels in people with severe ID is moderated by the presence of ASD suggest that the stress response system may function differently in people with ID and ASD than in the general population.

Co-morbid tics and stereotypies: a systematic literature review.

BACKGROUND: Tics and stereotypies are childhood-onset repetitive behaviours that can pose significant diagnostic challenges in clinical practice. Both tics and stereotypies are characterised by a complex co-morbidity profile, however little is known about the co-occurrence of these hyperkinetic disorders in the same patient population. OBJECTIVE: This review aimed to assess the relationship between tics and stereotypies when these conditions present in co-morbidity. METHODS: We conducted a systematic literature review of original studies on co-morbid tics and stereotypies, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Our literature search identified six studies of suitable sample size (n ≥ 40) presenting data on the association between tics and stereotypies in otherwise typically developing patients. A considerable proportion (23%) of patients diagnosed with stereotypic movement disorder present with co-morbid tics (range 18-43%). Likewise, the prevalence of primary stereotypies is increased in patients with tic disorders such as Tourette syndrome (8%, range 6-12%). DISCUSSION: Tics and stereotypies can often develop in co-morbidity. The association of tics and stereotypies in the same patient has practical implications, in consideration of the different treatment approaches. Future research should focus on the assessment and management of both conditions, particularly in special populations (e.g. patients with pervasive developmental disorders).

Case Reports: Clozapine for the Treatment of Catatonia in Autism Spectrum Disorder.

Catatonia is a severe clinical syndrome which has been increasingly reported in autism spectrum disorder (ASD). The prevalence of catatonia in ASD is unknown. Diagnosing catatonia in ASD is complicated by overlapping clinical features such as mutism, stereotypies, and echophenomena. Here, we present the clinical histories of two individuals with ASD and catatonia who were successfully treated with clozapine. We have reported on a novel potential treatment option for catatonia in ASD. Additional studies are needed to evaluate the safety, efficacy, and tolerability of clozapine for the treatment of catatonia in ASD.

Transtorno do movimento estereotipado associado ao atraso da linguagem: dados de estudos de caso que contribuem para o diagnóstico diferencial / Stereotyped movement disorder associated with language delay -: data from case report that contribute to differential diagnosis / Trastorno del movimiento estereotipado asociado con el retraso del lenguaje: datos de estudios de casos que contribuyen al diagnóstico diferencial

Introdução: Movimentos repetitivos associados a alterações de linguagem representam dois importantes sinais de alerta para os TEA (Transtornos do Espectro do Autismo). Ainda que, segundo pesquisas atuais, o atraso na aquisição da linguagem não faça parte do conjunto de características comumente observadas em crianças na primeira infância com Transtorno do Movimento Estereotipado (TME), a sua coocorrência pode ser mais comum do que se imagina, o que pode levar a diagnósticos falso positivo para os TEA. Objetivo: Caracterizar o processo desviante de aquisição da linguagem associado ao TME, buscando diferenciar das características específicas aos TEA. Método: A presente pesquisa apresenta o relato de caso de duas crianças, na faixa etária dos 30 aos 36 meses, com importante atraso na aquisição da fala associado à presença de movimentos estereotipados, com perfis considerados de risco para o autismo. Resultados: Na primeira avaliação as duas crianças apresentavam escore médio referente ao número de sinais de alerta para os TEA. Após intervenção de 6 meses, para diagnóstico diferencial, houve queda no número de sinais de risco, como remissão de alguns comportamentos característicos dos TEA, melhora na intensidade dos movimentos repetitivos e aumento do repertório de fala. Conclusão: Ainda que a presença de movimentos repetitivos ou estereotipadas seja um dos sinais clássicos dos TEA, mesmo que coocorra com outras alterações igualmente sugestivas a este diagnóstico, como o atraso na fala, para que o diagnóstico seja conclusivo, é necessária a observação da presença de outros sintomas que se manifestam de forma persistente ao longo do desenvolvimento.

Introduction: The repetitive movements associated with language disorders represent two important warning signs for ASD (Autism Spectrum Disorders). Even if, according to current research, the delay in language acquisition may not be part of the set of characteristics commonly observed in toddlers with Stereotyped Movement Disorder (SMD), this co-occurrence of language impairment and Stereotyped Movement Disorder may be more common than can be imagined, which leads to mistaken ASD diagnoses. Objective: To characterize the deviant language acquisition process associated with SMD, seeking to differentiate the specific characteristics of ASD. Method: This research presents a case report of two toddlers, aged 30 to 36 months, with an important delay in the acquisition and development of speech associated with the presence of stereotyped movements, with profiles considered at risk for autism. Results: The first assessment showed important results indicating ASD for both children. After a 6-month intervention, there was a decrease in the number of risk signs, such as remission of some behavior characteristic of ASD, improvement in the intensity of repetitive movements and increase of the speech repertoire. Conclusion: Although the presence of repetitive or stereotyped movements is one of the classic signs of ASD, even if it co-occurs with other disorders equally suggestive to this diagnosis, such as delayed speech, for a conclusive diagnosis it is necessary the observation of other symptoms that manifest themselves persistently throughout development.

Introducción: Los movimientos repetitivos asociados con los cambios de lenguaje representa importantes señales de advertencia para los TEA (Trastornos del Espectro Autista). Aunque, según la investigación actual, el retraso en la adquisición del lenguaje no es parte del conjunto de características comúnmente observadas en niños en la primera infancia con trastorno de movimientos estereotipados, su coocurrencia puede ser más común de lo imaginado, lo que conduce a diagnósticos falsos positivos de TEA. Objetivo: Caracterizar el proceso de adquisición del lenguaje desviado asociado al Trastorno de Movimientos Estereotipados (TME), buscando diferenciar las características específicas de los TEA. Método: Esta investigación presenta el caso clínico de dos niños, de 30 a 36 meses, con un importante retraso en la adquisición y desarrollo del habla asociado a la presencia de movimientos estereotipados, con perfiles considerados en riesgo de autismo. Resultados: En la primera evaluación, los dos niños obtuvieron una puntuación media con respecto al número de señales de advertencia de TEA. Después de una intervención de 6 meses, diagnóstico diferencial, hubo una disminución en el número de signos de riesgo, como la remisión de algunos comportamientos característicos de los TEA, una mejora en la intensidad de los movimientos repetitivos y un aumento en el repertorio del habla. Conclusión: Si bien la presencia de movimientos repetitivos o estereotipados es uno de los signos clásicos de los TEA, aunque concurra con otros cambios igualmente sugestivos para este diagnóstico, como el retraso en el habla, para que el diagnóstico sea concluyente es necesaria la observación de la observación. otros síntomas que se manifiestan de forma persistente a lo largo del desarrollo.

De novo nose-pinching stereotypy with somnolence: Clues to autoimmune encephalitis.

Autoimmune encephalitis (AE) is being increasingly recognized as a cause of new-onset movement disorders. Movement disorders in AE are diverse and range from hyperkinetic conditions such as oromandibular dyskinesias, tremors and chorea to hypokinetic ones such as bradykinesia and parkinsonism. Stereotypies have been described in association with anti-NMDAR encephalitis. Similarly, sleep dysfunction is an underrecognized feature in many AE subtypes, prominently anti-IgLON5 although the correlation of phenotype of sleep dysfunction with a particular antibody subtype in AE is unclear. Despite the recognition of both these features as part of an overreaching spectrum in any patient with AE, seldom are they the sole presenting manifestations. Additionally, the challenge is further compounded in a patient who has seronegative AE since neither sleep disturbances nor stereotypies have been well characterized with this condition yet, and the diagnosis is conditional to exhausting a list of ancillary supportive features. In this brief communication, we describe the case of a young man who presented with hypersomnolence and an unusual focal nose-pinching stereotypy of subacute onset who lacked the presence of other typical clinical characteristics such as cognitive/memory impairment and seizures and had negative autoimmune antibodies but responded to immune therapy dramatically. We propose that the presence of de novo hypersomnolence and stereotypy should inform a potential diagnosis of AE.

Sleep-related rhythmic movement disorder: A case report of head banging alopecia.

We present a case of alopecia associated with sleep-related rhythmic movement disorder (RMD) in an otherwise healthy 2-year-old boy. The alopecic patch he presented with on his scalp coincided with the location of repeated head banging in a video taken by the patient's mother. Alopecia secondary to RMD is an under recognized entity and should be included in the differential diagnosis of pediatric alopecia.

Development and Implementation of a Brain Rest Protocol in Nonintellectually Challenged Youth With Head-Banging Behaviors.

INTRODUCTION: Concussions as a result of mild traumatic brain injury (MTBI) in youth are often associated with athletic injury; however, they can also occur as a result of intentional self-injury by head banging. Despite the known neurological sequelae secondary to MTBI, assessment, interventions, and consequences of head banging in the nonintellectually disabled populations have not been well studied. AIMS: The intent of this nurse-led intervention was to develop a brain rest protocol at a residential treatment program serving youth who were between 12 and 19 years old in order to improve the quality of care and moderate negative sequelae resulting from MTBI. METHODS: A nursing assessment guided by an adaptation of the acute concussion evaluation and a strength-based intervention protocol was developed and applied to youth who engage in head banging. RESULTS: The result was a protocol that defined the process by which a youth would be assessed and treated after head banging. There are no outcome measures that would assist to measure the effectiveness of this intervention in the short or long term. CONCLUSION: This intervention filled a need for improved assessment and appropriate interventions in youth with head-banging behavior. It is feasible that the assessment and implementation of the brain rest protocol is the first step in understanding how to best evaluate and manage the sequelae of intentional head banging resulting from MTBI.

To What Extent Do Practitioners Need to Treat Stereotypy During Academic Tasks?

Researchers frequently argue that a child's engagement in stereotypy may compete with his ability to acquire academic skills, engage in appropriate social interactions, or both; however, few studies have directly tested these suppositions. We used a five-phase assessment to evaluate the extent to which behavioral interventions with a progressively greater number of components were necessary to decrease stereotypy and increase correct responding during academic instructions for five children diagnosed with autism spectrum disorders. For one participant, stereotypy decreased when instructors provided standard instruction without specific intervention for stereotypy. For two participants, stereotypy decreased when instructors provided standard instruction plus antecedent intervention for stereotypy with continuous music. For another participant, stereotypy decreased when instructors provided enhanced consequences for correct responding during standard instruction without either antecedent or consequent intervention for stereotypy. For the final participant, stereotypy decreased and correct responding increased when instructors provided standard instruction and consequent intervention for stereotypy.

Motor coordination impairment in children with autism spectrum disorder: a pilot study using Movement Assessment Battery for Children-2 Checklist.

BACKGROUND: Some research suggests that children with autism spectrum disorder (ASD) experience diverse motor difficulties that appear closely related to the severity of symptomatology, including repetitive behaviors. Therefore, motor assessment in ASD has crucial relevance in order to plan a specific intervention. The aim of this study is to assess and describe the motor functioning in school-aged children with ASD and to evaluate the relationship between their motor profile and clinical features. METHODS: The Movement Assessment Battery for Children - second edition (M-ABC2) Checklist was administered to twenty children with ASD, aged between 5 and 13.5 years. The motor profile of the sample was analyzed and then the relationship between the motor functioning and the clinical characteristics of subjects (age, treatment duration, intellectual functioning and repetitive behaviors) was investigated. RESULTS: Seventy percent of our sample has motor difficulties, especially in aiming and catching skills, balance and manual dexterity. Poorer performance was related to a higher frequency and intensity of repetitive and stereotyped behaviors. CONCLUSIONS: Motor difficulties in children with ASD affect specific skills that imply the ability to integrate the perception with the action for anticipating and controlling the movement in a well-coordinated way. This result, along with the finding of an increased severity of repetitive and stereotyped behaviors in these children, emphasizes the close link between motor and "core" symptoms in ASD.

Interrelationship Between Cognitive Control, Anxiety, and Restricted and Repetitive Behaviors in Children with 22q11.2 Deletion Syndrome.

Restricted and repetitive behaviors (RRB) are common in individuals with 22q11.2 microdeletion syndrome (22q11.2DS), yet the underlying mechanisms of these behaviors remain poorly characterized. In the present pilot investigation, we aimed to further our understanding of RRB in 22q11.2DS by exploring their relationship with cognitive control and anxiety as well as with sex, chronological age, and full-scale IQ. Parents of 38 children with 22q11.2DS (17 females; Mage = 11.15 years, SD = 2.46) completed the Social Communication Questionnaire as a measure of RRB and social and communication (SC) problems and the Behavioral Assessment System for Children-2 as a measure of anxiety and cognitive control. Higher RRB scores were significantly associated with higher anxiety levels (r = 0.44, P = 0.006), more impairments in cognitive control (r = 0.56, P < 0.001), and higher SC scores (r = 0.43, P = 0.011). In the first step of the hierarchical regression model, anxiety accounted for 24.5% of variance (F = 10.05, P = 0.003); cognitive control accounted for an additional 18.1% of variance (Fchange = 11.15, P < 0.001) in the second step; SC score accounted for only 0.8% of additional variance in the third step (Fchange = 0.40, P = 0.53). The final model explained 43.4% of variance (F = 7.42, P = 0.001), with cognitive control as a unique independent predictor of RRB score (t = 2.52, P = 0.01). The current study provides the first exploration of the cognitive control-anxiety-RRB link in individuals with 22q11.2DS and points to cognitive control as a potentially viable target for treatments aimed at reducing RRB. Autism Res 2019, 12: 1737-1744. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with 22q11.2 deletion syndrome show high levels of repetitive behaviors, however, the previous research has not explored why people with this syndrome exhibit high rates of repetitive behaviors. Understanding the reasons for the high levels of repetitive behaviors is important given that these behaviors can be highly impairing. Our study found that repetitive behaviors were associated with impaired ability to self-regulate and high levels of anxiety. These findings need to be further replicated; however, they are important as they suggest potentially promising ways of reducing these behaviors.

Psychometric analysis of the repetitive behavior scale-revised using confirmatory factor analysis in children with autism.

Research examining restricted and repetitive patterns of behavior or interests (RRB) in autism spectrum disorder (ASD) has increased our understanding of its contribution to diagnosis and its role in development. Advances in our knowledge of RRB are hindered by the inconsistencies in how RRB is measured. The present study examined the factor structure of the Repetitive Behavior Scale-Revised (RBS-R) in a sample of 350 children with ASD ages 2-9. Confirmatory factor analysis designed for items with categorical response types was implemented to examine six proposed structural models. The five-factor model demonstrated the most parsimonious fit based on common overall fit indices that was further supported by examination of local model fit indicators, though, the four- and six-factor models evidenced adequate-to-good fit as well. Examination of RRB factor score approaches indicated only minor differences between summed item subscale scores and extracted factor scores with regard to associations with diagnostic measures. All RRB subtypes demonstrated significant associations with cognitive functioning and adaptive behavior. Implications for future research validating the RBS-R as a more extensive clinical measure of RRB in ASD are discussed. Autism Res 2019, 12: 1399-1410. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Repetitive behaviors are one of the two main symptoms of autism spectrum disorder (ASD). To better understand the role of repetitive behaviors, we must establish effective ways of measuring them. This study assessed the measurement qualities of the Repetitive Behavior Scale-Revised (RBS-R) in a sample of 350 children with ASD ages 2-9. We found that the RBS-R measures multiple types of repetitive behaviors and that these behaviors are related to thinking ability and independence.

Atypical body movements during night in young children with autism spectrum disorder: a pilot study.

Children with autism spectrum disorder (ASD) reportedly suffer from sleep problems at a higher rate than typically developing (TD) children. Several previous studies have reported differences in sleep indices (e.g., sleep latency) in children with ASD. However, no previous studies have focused specifically on the time course of body movements. In the present study, we investigated the time course of body movements in young TD children and young children with ASD as well as the relationship between body movements during night and social ability. Seventeen TD children and 17 children with ASD participated in this study (5 to 8 years old). We used an accelerometer attached to the waist to record movements during night and measured the average time course of body movements for 3 nights. Our results demonstrated that the rate of body movement 2 to 3 hours after the onset of body stillness was higher in children with ASD than in TD children. In addition, the higher rate of body movement at 0.5 to 1 hour after the onset of body stillness was associated with a lower social ability in the children with ASD. Our results suggested that the time course of body movements is an objective behavioural index for young children with ASD.

Short report: Relationships between sensory processing, repetitive behaviors, anxiety, and intolerance of uncertainty in autism spectrum disorder and Williams syndrome.

Autism spectrum disorder (ASD) and Williams syndrome (WS) share psychopathology relating to sensory processing and repetitive behaviors. The relationships between the sensory features and repetitive behaviors in both disorders, and the mechanisms underlying these relationships are not well understood. The aim of this study was to examine the relationships between sensory processing, repetitive behaviors, anxiety, and intolerance of uncertainty in children with ASD and those with WS to better understand the complexity of psychopathology in these disorders. Parents of 19 children with ASD and 16 children with WS, aged between 4 and 9 years, were asked to complete questionnaires assessing their children's sensory experiences, anxiety symptoms, severity and frequency of repetitive behaviors, and level of intolerance of uncertainty. Serial mediation analysis was performed. Direct significant relationships between sensory features and repetitive behaviors were found only for the ASD group. The relationship between sensory processing difficulties and repetitive behaviors was mediated via intolerance of uncertainty in WS. The findings support the value of considering the complexity of the mechanisms underlying the relationship between sensory processing and repetitive behaviors across neurodevelopmental disorders and the mechanisms underlying these aspects of psychopathology in these groups. Understanding these relationships will shed light on some of the most challenging and intractable characteristics of both conditions and inform suitable interventions to improve quality of life for individuals with either ASD or WS. Autism Research 2019, 12: 759-765. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In autism spectrum disorder (ASD) and Williams syndrome (WS) difficulties processing the sensory aspects of the environment, repetitive behaviors and high levels of anxiety co-occur, but the relationships between these features are not well understood. This study found that sensory difficulties were directly associated with repetitive behaviors in children with ASD, but not WS, and in WS this relationship was mediated by intolerance of uncertainty. The findings support the value of considering the complexity of the mechanisms underlying the relationship between sensory processing and repetitive behaviors across neurodevelopmental disorders.

Using Mobile Technology to Reduce Engagement in Stereotypy: A Validation of Decision-Making Algorithms.

We developed an iOS app, the iSTIM, designed to support parents of children with autism spectrum disorders (ASD) in reducing common repetitive vocal and motor behavior (i.e., stereotypy). The purpose of our study was to preliminarily test the decision-making algorithms of the iSTIM using trained university students to implement the assessments and interventions. Specifically, we examined the effects of the iSTIM on stereotypy and functional engagement in 11 children with ASD within alternating treatment designs. Using the iSTIM reduced engagement in stereotypy for eight participants and increased functional engagement for four of those participants. Our results indicate that the iSTIM may decrease engagement in stereotypy but that some of the decision-making algorithms may benefit from modifications prior to testing with parents.

The autism spectrum phenotype in ADNP syndrome.

Pathogenic disruptions to the activity-dependent neuroprotector homeobox (ADNP) gene are among the most common heterozygous genetic mutations associated with autism spectrum disorders (ASDs). Individuals with ADNP disruptions share a constellation of medical and psychiatric features, including ASD, intellectual disability (ID), dysmorphic features, and hypotonia. However, the profile of ASD symptoms associated with ADNP may differ from that of individuals with another ASD-associated single gene disruption or with ASD without a known genetic cause. The current study examined the ASD phenotype in a sample of representative youth with ADNP disruptions. Participants (N = 116, ages 4-22 years) included a cohort with ADNP mutations (n = 11) and three comparison groups with either a mutation to CHD8 (n = 11), a mutation to another ASD-associated gene (other mutation; n = 53), or ASD with no known genetic etiology (idiopathic ASD; n = 41). As expected, individuals with ADNP disruptions had higher rates of ID but less severe social affect symptoms compared to the CHD8 and Idiopathic ASD groups. In addition, verbal intelligence explained more variance in social impairment in the ADNP group compared to CHD8, other mutation, and idiopathic ASD comparison groups. Restricted and repetitive behaviors in the ADNP group were characterized by high levels of stereotyped motor behaviors, whereas the idiopathic ASD group showed high levels of restricted interests. Taken together, these results underscore the role of ADNP in cognitive functioning and suggest that social impairments in ADNP syndrome are consistent with severity of verbal deficits. Autism Res 2018, 11: 1300-1310. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Disruptions to the ADNP gene (i.e., ADNP syndrome) have been associated with autism spectrum disorder (ASD). This article describes intellectual disability, mild social difficulties, and severe repetitive motor movements in a group of 11 youth with ADNP Syndrome. We found lower rates of ASD than previously reported. Verbal skills explained individual variability in social impairment. This pattern suggests that the ADNP gene is primarily associated with learning and memory, and level of social difficulties is consistent with level of verbal impairment.

Large Forehead Mass Resulting From Chronic Head Banging.

Head banging is a commonly observed movement disorder which is typically self-limited. Complications secondary to this behavior are rare. In this report, the authors present the case of a 15-year-old patient who was treated for a forehead mass which developed secondary to chronic head banging. Surgical excision was performed for treatment of the lesion. Results from surgical pathology were notable for fibrosis consistent with history of chronic head banging. Preoperative magnetic resonance imaging and physical examination were also consistent with this diagnosis. This is a rare clinical entity that should be considered in patients presenting with a forehead mass and a history of head banging.

Assessing the heterogeneity of autism spectrum symptoms in a school population.

The aim of the present study was to assess whether the nature of the main autistic features (i.e., social communication problems and repetitive and restrictive patterns) are better conceptualized as dimensional or categorical in a school population. The study was based on the teacher ratings of two different age groups: 2,585 children between the ages of 10 and 12 (Primary Education; PE) and 2,502 children between the ages of 3 and 5 (Nursery Education; NE) from 60 mainstream schools. The analyses were based on Factor Mixture Analysis, a novel approach that combines dimensional and categorical features and prevents spurious latent classes from appearing. The results provided evidence of the dimensionality of autism spectrum symptoms in a school age population. The distribution of the symptoms was strongly and positively skewed but continuous; and the prevalence of high-risk symptoms for autism spectrum disorders (ASD) and social-pragmatic communication disorder (SCD) was 7.55% of NE children and 8.74% in PE. A categorical separation between SCD and ASD was not supported by our sample. In view of the results, it is necessary to establish clear cut points for detecting and diagnosing autism and to develop specific and reliable tools capable of assessing symptom severity and functional consequences in children with ASD. Autism Res 2018, 11: 979-988. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The results of the present study suggest that the distribution of autism spectrum symptoms are continuous and dimensional among school-aged children and thus support the need to establish clear cut-off points for detecting and diagnosing autism. In our sample, the prevalence of high-risk symptoms for autism spectrum disorders and social-pragmatic communication disorder was around 8%.

Further delineation of the MECP2 duplication syndrome phenotype in 59 French male patients, with a particular focus on morphological and neurological features.

The Xq28 duplication involving the MECP2 gene (MECP2 duplication) has been mainly described in male patients with severe developmental delay (DD) associated with spasticity, stereotypic movements and recurrent infections. Nevertheless, only a few series have been published. We aimed to better describe the phenotype of this condition, with a focus on morphological and neurological features. Through a national collaborative study, we report a large French series of 59 affected males with interstitial MECP2 duplication. Most of the patients (93%) shared similar facial features, which evolved with age (midface hypoplasia, narrow and prominent nasal bridge, thick lower lip, large prominent ears), thick hair, livedo of the limbs, tapered fingers, small feet and vasomotor troubles. Early hypotonia and global DD were constant, with 21% of patients unable to walk. In patients able to stand, lower limbs weakness and spasticity led to a singular standing habitus: flexion of the knees, broad-based stance with pseudo-ataxic gait. Scoliosis was frequent (53%), such as divergent strabismus (76%) and hypermetropia (54%), stereotypic movements (89%), without obvious social withdrawal and decreased pain sensitivity (78%). Most of the patients did not develop expressive language, 35% saying few words. Epilepsy was frequent (59%), with a mean onset around 7.4 years of age, and often (62%) drug-resistant. Other medical issues were frequent: constipation (78%), and recurrent infections (89%), mainly lung. We delineate the clinical phenotype of MECP2 duplication syndrome in a large series of 59 males. Pulmonary hypertension appeared as a cause of early death in these patients, advocating its screening early in life.