Development and behaviour in Marshall-Smith syndrome: an exploratory study of cognition, phenotype and autism

Balkom, Ingrid D. C. van; Shaw, Adam; Vuijk, Pieter Jelle; Franssens, M.; Hoek, Hans W.; Hennekam, Raoul C. M.

doi:10.1111/j.1365-2788.2011.01451.x

Cited by 18 publications

(34 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have previously assessed cognition, behavioural phenotype, and autism in Marshall-Smith syndrome (MSS), a very rare entity characterized by failure to thrive, developmental delay, abnormal bone maturation, and a characteristic face. In comparison with the MSS study with a similar methodology, 17 the findings in the present study indicate that in classic PTHS the behavioural phenotype is clearly similar to behaviours seen in ASD. This can be noted not only in the difficulties in engaging and communicating with others, but also in the much higher occurrence and level of severity of repetitive motor stereotypies, repetitive play and fascination with specific objects, and difficulties with changes in daily activities or routines.…”

Section: Discussionsupporting

confidence: 66%

“…The child psychiatrist is experienced in assessing individuals with autism and other developmental disabilities. 3,17 In-person interviews with parents were used to assess past and current development, and functioning for the domains communication, (adaptive) behaviour, and social-emotional development. Parents were invited to provide further information through a standardized questionnaire assessing emotional and behavioural problems.…”

Section: Test Instrumentsmentioning

confidence: 99%

“…Indeed the ADI-R has previously been used with individuals functioning below a mental age of 24 months, as there is a dearth of adequate instruments available for individuals with intellectual disability and possible comorbid ASD. 17,24 Vineland Adaptive Behaviour Scales…”

Section: Autism Diagnostic Interview -Revisedmentioning

confidence: 99%

See 2 more Smart Citations

Development, cognition, and behaviour in Pitt–Hopkins syndrome

Balkom

Vuijk²,

Franssens

et al. 2012

Develop Med Child Neuro

View full text Add to dashboard Cite

ABBREVIATIONSASD Autism spectrum disorder PTHS Pitt-Hopkins syndrome AIM The aim of the study was to collect detailed data on behavioural, adaptive, and psychological functioning in 10 individuals with Pitt-Hopkins syndrome (PTHS), with specific attention to manifestations of autism spectrum disorder (ASD).METHOD The participants (four females, six males), residing in the Netherlands and Belgium, were ascertained through the Dutch national PTHS support group. Median age of participants was 10 years, the age range was between 32 and 289 months. They underwent psychiatric examinations and neuropsychological measurements using a comprehensive assessment battery. Additionally, parental information was gathered through standardized interviews and questionnaires. Findings were compared with those from the literature.RESULTS All participants showed profound intellectual disability, amiable demeanour with minimal maladaptive behaviours, severe impairments of communication and language, and intense, frequent motor stereotypies. Impairments in all participants were beyond what would be expected for cognitive abilities, fitting a classification of ASD.INTERPRETATION Patients with PTHS are characterized not only by specific physical and genetic manifestations but also by specific behavioural and cognitive characteristics. Studying behaviour and cognition may improve diagnosis and prognosis, allows recognition of comorbidities, and contributes to adequate counselling of families.Pitt-Hopkins syndrome (PTHS) is characterized by intellectual disability, distinctive facial characteristics, breathing abnormalities, and repetitive behaviours. It is caused by genetic deletions ⁄ mutations resulting in TCF4 haploinsufficiency. To date, some 66 patients with confirmed TCF4 changes have been studied worldwide, mainly investigating somatic and genetic aspects.Early descriptions of PTHS in individuals with intellectual disability emphasized an abnormal breathing pattern, distinctive facial features, and postnatal microcephaly. Further definition of the PTHS phenotype in later publications included severe developmental delays in motor and speech ⁄ language development, episodic diurnal hyperventilation with apnoea, and frequent epilepsy.1-5 Three causes of PTHS have been identified. The dominant form of PTHS is caused by deletions ⁄ mutations in Transcription Factor 4 (TCF4) on chromosome 18 at 18q21. [6][7][8][9][10][11][12][13][14] Recessive forms of a PTHS-like disorder are caused by mutations in NeuReXiN1 (NRXN1) on chromosome 2 and CoNTactiN Associated Protein-like 2 (CNT-NAP2) on chromosome 7. 15,16 As studies of the syndrome have accumulated, it has become clear that not all individuals with molecularly confirmed alterations show intermittent overbreathing. Most studies of individuals with PTHS have reported severe developmental delay and intellectual disability, motor abnormalities (late or absent walking, repetitive movements of hands and head), and behavioural traits such as autistic symptoms; a quiet, friendly disposition in ...

show abstract

Section: Discussionsupporting

confidence: 66%

Section: Test Instrumentsmentioning

confidence: 99%

See 1 more Smart Citation

Development, cognition, and behaviour in Pitt–Hopkins syndrome

Balkom

Vuijk²,

Franssens

et al. 2012

Develop Med Child Neuro

View full text Add to dashboard Cite

show abstract

“…Both of these conditions are characterised by overgrowth, musculoskeletal abnormalities, abnormal behaviour including autistic traits, and mild to moderate learning difficulties. Magnetic resonance imaging analyses have shown that these individuals recapitulate some of the gross defects observed in the homozygous Nfix knockout mouse, including hypoplasia of the corpus callosum and ventricular dilation [42], [43]. Although no gross defects in hippocampal morphology were reported in these studies, our results suggest that individuals with these disorders may exhibit subtle defects in hippocampal morphology and hippocampal-dependent behaviour, and that this could contribute to their neurological deficits.…”

Section: Discussionmentioning

confidence: 49%

Heterozygosity for Nuclear Factor One X Affects Hippocampal-Dependent Behaviour in Mice

et al. 2013

View full text Add to dashboard Cite

Identification of the genes that regulate the development and subsequent functioning of the hippocampus is pivotal to understanding the role of this cortical structure in learning and memory. One group of genes that has been shown to be critical for the early development of the hippocampus is the Nuclear factor one (Nfi) family, which encodes four site-specific transcription factors, NFIA, NFIB, NFIC and NFIX. In mice lacking Nfia, Nfib or Nfix, aspects of early hippocampal development, including neurogenesis within the dentate gyrus, are delayed. However, due to the perinatal lethality of these mice, it is not clear whether this hippocampal phenotype persists to adulthood and affects hippocampal-dependent behaviour. To address this we examined the hippocampal phenotype of mice heterozygous for Nfix (Nfix +/−), which survive to adulthood. We found that Nfix +/− mice had reduced expression of NFIX throughout the brain, including the hippocampus, and that early hippocampal development in these mice was disrupted, producing a phenotype intermediate to that of wild-type mice and Nfix−/− mice. The abnormal hippocampal morphology of Nfix +/− mice persisted to adulthood, and these mice displayed a specific performance deficit in the Morris water maze learning and memory task. These findings demonstrate that the level of Nfix expression during development and within the adult is essential for the function of the hippocampus during learning and memory.

show abstract

“…Osteopenia, nontraumatic fractures, and other bony and connective tissue findings have been described during childhood (Flatz and Natzschka, 1978;Adam et al, 2005). Cryptorchidism, anteriorly placed anus, hypospadias, vesicoureteral reflux, pyloric stenosis, gingival hypertrophy, Wilms tumor, IgA deficiency, pigmentary skin defects (Passalacqua et al, 2011), hypoplasia of the labia majora, labia minora, and clitoral hood (Diab et al, 2003), and developmental and behavioral alterations have been reported previously (Van Balkom et al, 2011), but there has been no description of hypertrophic labia minora and clitoris as in this current patient. The frequent and significant respiratory difficulties in MSS result from a combination of pathologies, which mainly comprise upper airway obstruction (retrognathia, choanal stenosis, abnormal larynx, and laryngomalacia) and aspiration pneumonia.…”

Section: Discussionmentioning

confidence: 89%