Diagnosis and management in Rubinstein-Taybi syndrome:first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.</p

Diagnosis and management in Rubinstein-Taybi syndrome: first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care

Caractéristiques du phénotype développemental, cognitif, socio-émotionnel et socio-adaptatif des enfants porteurs du syndrome de Rubinstein-Taybi. Etude comparative avec une population d’enfants porteurs de Trisomie 21

Context: still little known, Rubinstein and Taybi syndrome (RTS) is a rare genetic syndrome whose incidence is estimated between 1/100,000 and 1/125,000. RTS is characterized by intellectual disability, mental retardation, growth, extremity abnormalities with large thumbs and big toes, and facial dysmorphism. While research highlights a set of behaviors characteristic of children with Rubinstein-Taybi Syndrome, the only ones relating to development essentially highlight intellectual retardation with varying degrees of severity (IQ between 30 and 70, with an average of at IQ 40-45) and expressive language difficulties. Objective: this study aimed to explore the developmental phenotype of children with Rubinstein- Taybi Syndrome using the model of the cross-syndromic behavioural approach. It is a question of deepening the psychomotor, cognitive and socio-emotional development but also the socioemotional behavior of these children, by comparing, to better specify, their developmental profile to that of other children with intellectual disabilities with genetic syndrome (Down’s syndrome). Method: study’s participants were recruited from the medical genetics department (Bordeaux CHU). The sample brings together 150 children (101 boys, 49 girls) divided into two groups: 85 children with RTS and 65 children with Down’s syndrome. The children are evaluated using 4 instruments but according to pairings with variable numbers; the BL-R, Brunet-Lézine's early childhood psychomotor development scale (Josse, 2001), the BECS, Cognitive and socio-emotional assessment battery (Adrien, 2007), the PEP-3, Psycho-Educational Profile –3 (Schopler & al., 2010) and the Vineland-II, the socio-adaptive behavior rating scale (Sparrow & al., 2015). An information note and a consent form were given to the parents to obtain their agreement to use the results of their child's psychological assessments for this study. Results: a first study highlights a characteristic development profile in the SRT children of this group with strong points in the Postural domains, Hand-eye Coordination, Emotional Expression, Autonomy and Socialization and points weak in the areas of Expressive Language, Symbolic Play, Vocal Imitation, Communication and Interpersonal Relations. Socio-emotional heterogeneity is more important than cognitive heterogeneity. A second comparative study shows that the developmental profile of SRT children is more deficient than that of children with Trisomy 21. SRT children differ significantly from children with Trisomy 21 in the areas of joint attention and emotional expression. Conclusion: this study highlighted developmental characteristics in children with RTS. Improving the knowledge of these children will allow reflection on the implementation of psycho-educational programs specific to their profile with a view to considering personalized interventions and informing professionals of the particularities of this syndrome.Contexte : encore peu connu, le syndrome de Rubinstein et Taybi (SRT) est un syndrome génétique rare dont la prévalence à la naissance est estimée entre 1/100 000 et 1/125 000. Le SRT se caractérise par une déficience intellectuelle, un retard de croissance, des anomalies des extrémités avec des pouces et des gros orteils larges et une dysmorphie faciale. Si les recherches mettent en évidence un ensemble de comportements caractéristiques des enfants porteurs du Syndrome de Rubinstein- Taybi, les seules portant sur le développement psychologique soulignent essentiellement le retard intellectuel avec des degrés divers de sévérité (QI compris entre 30 et 70, avec une moyenne située au QI 40-45) et des difficultés de langage expressif. Objectif : le but de l’étude est de décrire de façon exploratoire le phénotype développemental des enfants porteurs du Syndrome de Rubinstein-Taybi en utilisant le modèle de l’approche cross syndromique comportemental. Il s’agit d’approfondir le développement psychomoteur, cognitif et socio-émotionnel mais aussi le comportement socio-adaptatif de ces enfants, en comparant, pour mieux le spécifier, leur profil développemental à celui d’autres enfants ayant un handicap intellectuel avec syndrome génétique (Trisomie 21). Méthode : Les participants de l’étude sont recrutés au sein du service de génétique médicale (CHU BORDEAUX). L’échantillon rassemble 150 enfants (101 garçons, 49 filles) répartis en deux groupes 85 enfants avec un SRT et 65 enfants porteurs de TR21. Les enfants sont évalués à l’aide de 4 instruments mais selon des appariements à effectifs variables ; le BL-R, échelle de développement psychomoteur de la première enfance de Brunet-Lézine (Josse, 2001), la BECS, Batterie d’Evaluation Cognitive et socio-émotionnelle (Adrien, 2007), le PEP-3, Profil Psycho-Educatif–3 (Schopler & al., 2010) et la Vineland-II, l’échelle d’évaluation du comportement socio-adaptatif (Sparrow & al., 2015). Une note d’information et un formulaire de consentement ont été remis aux parents pour obtenir leur accord afin d’utiliser les résultats des évaluations psychologiques de leur enfant pour cette étude. Résultats : une première étude met en évidence un profil de développement caractéristique chez les enfants SRT de ce groupe avec des points forts dans les domaines Postural, Coordination oculo-manuelle, Expression Emotionnelle, Autonomie et Socialisation et des points faibles dans les domaines Langage expressif, Jeu symbolique, Imitation vocale, Communication et Relations interpersonnelles. Une hétérogénéité socio-émotionnelle est plus importante que l’hétérogénéité cognitive. Une seconde étude comparative montre que le profil développemental des enfants SRT est plus déficitaire que celui des enfants avec Trisomie 21. Les enfants SRT se différencient significativement des enfants avec Trisomie 21 dans les domaines de l’attention conjointe et de l’expression émotionnelle. Conclusion : cette étude a permis de mettre en évidence des caractéristiques développementales chez les enfants avec un SRT. L’amélioration des connaissances de ces enfants permettra des réflexions sur des mises en place de programmes psycho-éducatifs spécifiques à leur profil en vue d’envisager des interventions personnalisées et d’informer les professionnels des particularités de ce syndrome

Characteristics of the developmental, cognitive, socio-emotional and socio-adaptive phenotype of children with Rubinstein-Taybi Syndrome. Comparative study with a population of children with Down’s syndrome

Contexte : encore peu connu, le syndrome de Rubinstein et Taybi (SRT) est un syndrome génétique rare dont la prévalence à la naissance est estimée entre 1/100 000 et 1/125 000. Le SRT se caractérise par une déficience intellectuelle, un retard de croissance, des anomalies des extrémités avec des pouces et des gros orteils larges et une dysmorphie faciale. Si les recherches mettent en évidence un ensemble de comportements caractéristiques des enfants porteurs du Syndrome de Rubinstein- Taybi, les seules portant sur le développement psychologique soulignent essentiellement le retard intellectuel avec des degrés divers de sévérité (QI compris entre 30 et 70, avec une moyenne située au QI 40-45) et des difficultés de langage expressif. Objectif : le but de l’étude est de décrire de façon exploratoire le phénotype développemental des enfants porteurs du Syndrome de Rubinstein-Taybi en utilisant le modèle de l’approche cross syndromique comportemental. Il s’agit d’approfondir le développement psychomoteur, cognitif et socio-émotionnel mais aussi le comportement socio-adaptatif de ces enfants, en comparant, pour mieux le spécifier, leur profil développemental à celui d’autres enfants ayant un handicap intellectuel avec syndrome génétique (Trisomie 21). Méthode : Les participants de l’étude sont recrutés au sein du service de génétique médicale (CHU BORDEAUX). L’échantillon rassemble 150 enfants (101 garçons, 49 filles) répartis en deux groupes 85 enfants avec un SRT et 65 enfants porteurs de TR21. Les enfants sont évalués à l’aide de 4 instruments mais selon des appariements à effectifs variables ; le BL-R, échelle de développement psychomoteur de la première enfance de Brunet-Lézine (Josse, 2001), la BECS, Batterie d’Evaluation Cognitive et socio-émotionnelle (Adrien, 2007), le PEP-3, Profil Psycho-Educatif–3 (Schopler & al., 2010) et la Vineland-II, l’échelle d’évaluation du comportement socio-adaptatif (Sparrow & al., 2015). Une note d’information et un formulaire de consentement ont été remis aux parents pour obtenir leur accord afin d’utiliser les résultats des évaluations psychologiques de leur enfant pour cette étude. Résultats : une première étude met en évidence un profil de développement caractéristique chez les enfants SRT de ce groupe avec des points forts dans les domaines Postural, Coordination oculo-manuelle, Expression Emotionnelle, Autonomie et Socialisation et des points faibles dans les domaines Langage expressif, Jeu symbolique, Imitation vocale, Communication et Relations interpersonnelles. Une hétérogénéité socio-émotionnelle est plus importante que l’hétérogénéité cognitive. Une seconde étude comparative montre que le profil développemental des enfants SRT est plus déficitaire que celui des enfants avec Trisomie 21. Les enfants SRT se différencient significativement des enfants avec Trisomie 21 dans les domaines de l’attention conjointe et de l’expression émotionnelle. Conclusion : cette étude a permis de mettre en évidence des caractéristiques développementales chez les enfants avec un SRT. L’amélioration des connaissances de ces enfants permettra des réflexions sur des mises en place de programmes psycho-éducatifs spécifiques à leur profil en vue d’envisager des interventions personnalisées et d’informer les professionnels des particularités de ce syndrome.Context: still little known, Rubinstein and Taybi syndrome (RTS) is a rare genetic syndrome whose incidence is estimated between 1/100,000 and 1/125,000. RTS is characterized by intellectual disability, mental retardation, growth, extremity abnormalities with large thumbs and big toes, and facial dysmorphism. While research highlights a set of behaviors characteristic of children with Rubinstein-Taybi Syndrome, the only ones relating to development essentially highlight intellectual retardation with varying degrees of severity (IQ between 30 and 70, with an average of at IQ 40-45) and expressive language difficulties. Objective: this study aimed to explore the developmental phenotype of children with Rubinstein- Taybi Syndrome using the model of the cross-syndromic behavioural approach. It is a question of deepening the psychomotor, cognitive and socio-emotional development but also the socioemotional behavior of these children, by comparing, to better specify, their developmental profile to that of other children with intellectual disabilities with genetic syndrome (Down’s syndrome). Method: study’s participants were recruited from the medical genetics department (Bordeaux CHU). The sample brings together 150 children (101 boys, 49 girls) divided into two groups: 85 children with RTS and 65 children with Down’s syndrome. The children are evaluated using 4 instruments but according to pairings with variable numbers; the BL-R, Brunet-Lézine's early childhood psychomotor development scale (Josse, 2001), the BECS, Cognitive and socio-emotional assessment battery (Adrien, 2007), the PEP-3, Psycho-Educational Profile –3 (Schopler & al., 2010) and the Vineland-II, the socio-adaptive behavior rating scale (Sparrow & al., 2015). An information note and a consent form were given to the parents to obtain their agreement to use the results of their child's psychological assessments for this study. Results: a first study highlights a characteristic development profile in the SRT children of this group with strong points in the Postural domains, Hand-eye Coordination, Emotional Expression, Autonomy and Socialization and points weak in the areas of Expressive Language, Symbolic Play, Vocal Imitation, Communication and Interpersonal Relations. Socio-emotional heterogeneity is more important than cognitive heterogeneity. A second comparative study shows that the developmental profile of SRT children is more deficient than that of children with Trisomy 21. SRT children differ significantly from children with Trisomy 21 in the areas of joint attention and emotional expression. Conclusion: this study highlighted developmental characteristics in children with RTS. Improving the knowledge of these children will allow reflection on the implementation of psycho-educational programs specific to their profile with a view to considering personalized interventions and informing professionals of the particularities of this syndrome

Characteristics of the developmental, cognitive, socio-emotional and socio-adaptive phenotype of children with Rubinstein-Taybi Syndrome. Comparative study with a population of children with Down’s syndrome

Contexte : encore peu connu, le syndrome de Rubinstein et Taybi (SRT) est un syndrome génétique rare dont la prévalence à la naissance est estimée entre 1/100 000 et 1/125 000. Le SRT se caractérise par une déficience intellectuelle, un retard de croissance, des anomalies des extrémités avec des pouces et des gros orteils larges et une dysmorphie faciale. Si les recherches mettent en évidence un ensemble de comportements caractéristiques des enfants porteurs du Syndrome de Rubinstein- Taybi, les seules portant sur le développement psychologique soulignent essentiellement le retard intellectuel avec des degrés divers de sévérité (QI compris entre 30 et 70, avec une moyenne située au QI 40-45) et des difficultés de langage expressif. Objectif : le but de l’étude est de décrire de façon exploratoire le phénotype développemental des enfants porteurs du Syndrome de Rubinstein-Taybi en utilisant le modèle de l’approche cross syndromique comportemental. Il s’agit d’approfondir le développement psychomoteur, cognitif et socio-émotionnel mais aussi le comportement socio-adaptatif de ces enfants, en comparant, pour mieux le spécifier, leur profil développemental à celui d’autres enfants ayant un handicap intellectuel avec syndrome génétique (Trisomie 21). Méthode : Les participants de l’étude sont recrutés au sein du service de génétique médicale (CHU BORDEAUX). L’échantillon rassemble 150 enfants (101 garçons, 49 filles) répartis en deux groupes 85 enfants avec un SRT et 65 enfants porteurs de TR21. Les enfants sont évalués à l’aide de 4 instruments mais selon des appariements à effectifs variables ; le BL-R, échelle de développement psychomoteur de la première enfance de Brunet-Lézine (Josse, 2001), la BECS, Batterie d’Evaluation Cognitive et socio-émotionnelle (Adrien, 2007), le PEP-3, Profil Psycho-Educatif–3 (Schopler & al., 2010) et la Vineland-II, l’échelle d’évaluation du comportement socio-adaptatif (Sparrow & al., 2015). Une note d’information et un formulaire de consentement ont été remis aux parents pour obtenir leur accord afin d’utiliser les résultats des évaluations psychologiques de leur enfant pour cette étude. Résultats : une première étude met en évidence un profil de développement caractéristique chez les enfants SRT de ce groupe avec des points forts dans les domaines Postural, Coordination oculo-manuelle, Expression Emotionnelle, Autonomie et Socialisation et des points faibles dans les domaines Langage expressif, Jeu symbolique, Imitation vocale, Communication et Relations interpersonnelles. Une hétérogénéité socio-émotionnelle est plus importante que l’hétérogénéité cognitive. Une seconde étude comparative montre que le profil développemental des enfants SRT est plus déficitaire que celui des enfants avec Trisomie 21. Les enfants SRT se différencient significativement des enfants avec Trisomie 21 dans les domaines de l’attention conjointe et de l’expression émotionnelle. Conclusion : cette étude a permis de mettre en évidence des caractéristiques développementales chez les enfants avec un SRT. L’amélioration des connaissances de ces enfants permettra des réflexions sur des mises en place de programmes psycho-éducatifs spécifiques à leur profil en vue d’envisager des interventions personnalisées et d’informer les professionnels des particularités de ce syndrome.Context: still little known, Rubinstein and Taybi syndrome (RTS) is a rare genetic syndrome whose incidence is estimated between 1/100,000 and 1/125,000. RTS is characterized by intellectual disability, mental retardation, growth, extremity abnormalities with large thumbs and big toes, and facial dysmorphism. While research highlights a set of behaviors characteristic of children with Rubinstein-Taybi Syndrome, the only ones relating to development essentially highlight intellectual retardation with varying degrees of severity (IQ between 30 and 70, with an average of at IQ 40-45) and expressive language difficulties. Objective: this study aimed to explore the developmental phenotype of children with Rubinstein- Taybi Syndrome using the model of the cross-syndromic behavioural approach. It is a question of deepening the psychomotor, cognitive and socio-emotional development but also the socioemotional behavior of these children, by comparing, to better specify, their developmental profile to that of other children with intellectual disabilities with genetic syndrome (Down’s syndrome). Method: study’s participants were recruited from the medical genetics department (Bordeaux CHU). The sample brings together 150 children (101 boys, 49 girls) divided into two groups: 85 children with RTS and 65 children with Down’s syndrome. The children are evaluated using 4 instruments but according to pairings with variable numbers; the BL-R, Brunet-Lézine's early childhood psychomotor development scale (Josse, 2001), the BECS, Cognitive and socio-emotional assessment battery (Adrien, 2007), the PEP-3, Psycho-Educational Profile –3 (Schopler & al., 2010) and the Vineland-II, the socio-adaptive behavior rating scale (Sparrow & al., 2015). An information note and a consent form were given to the parents to obtain their agreement to use the results of their child's psychological assessments for this study. Results: a first study highlights a characteristic development profile in the SRT children of this group with strong points in the Postural domains, Hand-eye Coordination, Emotional Expression, Autonomy and Socialization and points weak in the areas of Expressive Language, Symbolic Play, Vocal Imitation, Communication and Interpersonal Relations. Socio-emotional heterogeneity is more important than cognitive heterogeneity. A second comparative study shows that the developmental profile of SRT children is more deficient than that of children with Trisomy 21. SRT children differ significantly from children with Trisomy 21 in the areas of joint attention and emotional expression. Conclusion: this study highlighted developmental characteristics in children with RTS. Improving the knowledge of these children will allow reflection on the implementation of psycho-educational programs specific to their profile with a view to considering personalized interventions and informing professionals of the particularities of this syndrome

Etude préliminaire du développement psychomoteur, cognitif et socio-émotionnel d’enfants porteurs du Syndrome de Rubinstein-Taybi

International audienc

Etude préliminaire du développement psychomoteur, cognitif et socio-émotionnel d’enfants porteurs du Syndrome de Rubinstein-Taybi

International audienc

Psychomotor, cognitive, and socio-emotional developmental profiles of children with Rubinstein-Taybi Syndrome and a severe intellectual disability

Background: Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomaly syndrome characterised by several typical somatic characteristics and by developmental disabilities with various degrees of severity. Focusing on children with RSTS, the aim of this study was to describe their psychomotor, cognitive, and socio-emotional developmental profiles.Method: Twenty-three children with RSTS (12 boys; 11 girls; mean chronological age: 4 years and 10 months) with severe intellectual disability (mean developmental quotient = 32.39) were recruited from an Expert Department of Medical Genetics. Developmental assessments were carried out with the Brunet-Lézine-Revised scale and the Social Cognitive Evaluation Battery.Results: The participants’ developmental profiles were characterised by heterogeneous psychomotor development, homogeneous cognitive and socio-emotional development, by more severe delays in expressive language, vocal imitation, and symbolic play skills, and by better developmental levels in socio-emotional abilities.Conclusions: Based on these atypical developmental profiles, early interventions should target the three most delayed abilities

A comparative study of cognitive and socio-emotional development in children with Rubinstein-Taybi syndrome and children with Autism Spectrum Disorder associated with a severe intellectual disability, and in young typically developing children with matched developmental ages

BACKGROUND: Cognitive and socio-emotional profiles of children with CREBBP-related Rubinstein-Taybi syndrome (RSTS 1), children with Autism Spectrum Disorder (ASD) with severe intellectual disability and developmental ages (DA) under 24 months, and typically developing (TD) children with similar DA were compared. PARTICIPANTS: Thirty-one children with RSTS 1 (mean chronological age, CA = 59,8 months; 33-87) and thirty children with ASD, matched on CA and DA and developmental quotients (DQ), were compared to thirty TD children (CA ranged from 12 to 24 months). METHODS: Cognitive and socio-emotional developmental levels, DA and DQ were assessed with appropriated tests. RESULTS: More socio-emotional developmental similarities were observed between TD and RSTS 1 than between TD and ASD children. Clinical groups displayed similar developmental delays in cognitive (self-image, symbolic play, means-ends, and object permanence) and socio-emotional domains (language and imitation). Children with RSTS 1 exhibited higher developmental levels in behavior regulation, joint attention, affective relations, emotional expression domains, and a lower developmental level in spatial relations domain. CONCLUSIONS: Common interventions centered on symbolic play, self-image, language, and imitation for both clinical groups, and differentiated interventions centered on spatial abilities for RSTS 1 children and on social abilities for ASD could be used by caregivers were suggested

Towards a new point of view on the phenotype of patients with a 17q12 microdeletion syndrome

International audienceOBJECTIVE:17q12 microdeletion syndrome involves 15 genes, including HNF1B, and is considered to confer a high risk of neuropsychiatric disorders. Patients with HNF1B gene deletion diagnosed secondary to renal disorders are only very rarely reported to have neuropsychiatric disorders. Interestingly, however, when tested, patients with HNF1B gene deletion are found to have 17q12 deletion. This brings into question the extent to which 17q12 deletion is genuinely associated with severe neuropsychological disorders and in which patients. In this study, we sought to confirm 17q12 microdeletion in kidney patients initially diagnosed with HNF1B gene deletion and evaluate neuropsychological disorders in these patients compared with those with HNF1B point mutation.PATIENTS AND DESIGN:Thirty-nine children with HNF1B disorders (26 with deletions) diagnosed secondary to renal abnormalities were included in this prospective study and tested for 17q12 microdeletion and neuropsychological disorders.RESULTS:The same 17q12 microdeletion found in patients with neuropsychological disorders was identified in all of our patients with HNF1B deletion. Neurological examinations found no severe impairments except for one patient with autism. No significant differences were found between patients with deletions and those with point mutations as concerns learning abilities and schooling. Nevertheless, patients with deletions tended to have lower developmental quotients and more difficulties at school.CONCLUSIONS:Complete deletion of the HNF1B gene and 17q12 microdeletion syndrome are actually the same genetic disorder. The neuropsychological phenotype of patients appears less severe when 17q12 deletion is diagnosed secondary to kidney rather than neuropsychological abnormalities. These data may influence antenatal counselling