Is macrocephaly a neural marker of a local bias in autism?

O’Reilly, Helen; Thiébaut, Flora I.; White, Sarah

doi:10.1016/j.dcn.2013.09.002

Cited by 3 publications

(1 citation statement)

References 40 publications

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“…Several studies from the USA and Europe estimate the prevalence of macrocephaly within ASD to be around 20 % [16,22]. Macrocephaly within ASD is linked to increased brain mass and white matter volumes, local processing bias, and genetic syndromes like PTEN hamartoma tumor syndrome (PHTS) that have clinically actionable adult phenotypes [16,23,24]. Combined with ease of measurement, these associations make macrocephaly an important endophenotype within ASD, worthy of deeper study.…”

Section: Connecting Phenotype and Genotype Across The Lifespanmentioning

confidence: 99%

Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder

2015

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Germline mutations in PTEN, which encodes a widely expressed phosphatase, was mapped to 10q23 and identified as the susceptibility gene for Cowden syndrome, characterized by macrocephaly and high risks of breast, thyroid, and other cancers. The phenotypic spectrum of PTEN mutations expanded to include autism with macrocephaly only 10 years ago. Neurological studies of patients with PTENassociated autism spectrum disorder (ASD) show increases in cortical white matter and a distinctive cognitive profile, including delayed language development with poor working memory and processing speed. Once a germline PTEN mutation is found, and a diagnosis of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome made, the clinical outlook broadens to include higher lifetime risks for multiple cancers, beginning in childhood with thyroid cancer. First described as a tumor suppressor, PTEN is a major negative regulator of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling pathway-controlling growth, protein synthesis, and proliferation. This canonical function combines with less well-understood mechanisms to influence synaptic plasticity and neuronal cytoarchitecture. Several excellent mouse models of Pten loss or dysfunction link these neural functions to autism-like behavioral abnormalities, such as altered sociability, repetitive behaviors, and phenotypes like anxiety that are often associated with ASD in humans. These models also show the promise of mTOR inhibitors as therapeutic agents capable of reversing phenotypes ranging from overgrowth to low social behavior. Based on these findings, therapeutic options for patients with PTEN hamartoma tumor syndrome and ASD are coming into view, even as new discoveries in PTEN biology add complexity to our understanding of this master regulator.

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Section: Connecting Phenotype and Genotype Across The Lifespanmentioning

confidence: 99%

Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder

2015

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Neurodevelopmental disorders in children with macrocephaly: A prevalence study and PTEN gene analysis

Kurata

Shirai

Saito

et al. 2018

Brain and Development

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Head circumference growth in children with Autism Spectrum Disorder: trend and clinical correlates in the first five years of life

Cirnigliaro,

Clericò,

Russo

et al. 2024

Front. Psychiatry

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BackgroundMacrocephaly is described in almost 15% of children with Autism Spectrum Disorder (ASD). Relationships between head growth trajectories and clinical findings in ASD children show a high degree of variability, highlighting the complex heterogeneity of the disorder.ObjectivesThe aim of this study was to measure differences of the early growth trajectory of head circumference (HC) in children with ASD and macrocephaly compared to ASD normocephalic children, examining clinical correlates in the two groups of patients.MethodsHC data were collected from birth to 5 years of age in a sample of children with a confirmed diagnosis of ASD. Participants were classified into two groups: ASD macrocephaly (ASD-M, Z-scores ≥1.88 in at least two consecutive HC measurements), and ASD non-macrocephaly (ASD-N). Based on the distribution of HC measurements (Z-scores), five age groups were identified for the longitudinal study. Developmental and behavioral characteristics of the ASD-M children compared to the ASD-N group were compared by using standardized scores.Results20,8% of the children sample met criteria for macrocephaly. HC values became indicative of macrocephaly in the ASD-M group at the age range from 1 to 6 months, and persisted thereafter throughout the first five years of age. ASD-M children showed significantly higher developmental quotients of Griffiths III B and D subscales compared to ASD-N group. No significant differences in the severity of ASD symptoms assessed by ADOS-2 were observed between ASD-M and ASD-N groups.ConclusionIn this study HC size from birth to 5 years links to accelerated HC growth rate as early as the first 6 months of age in children with ASD and macrocephaly, preceding the onset and diagnosis of ASD. We found that in early childhood, children with ASD-M may exhibit some advantages in language and social communication and emotional skills without differences in autism severity, when compared with age-matched normocephalic ASD children. Longitudinal analyses are required to catch-up prospectively possible relationships between head size as proxy measure of brain development and neuro-developmental and behavioral features in children with ASD.

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Is macrocephaly a neural marker of a local bias in autism?

Cited by 3 publications

References 40 publications

Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder

Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder

Neurodevelopmental disorders in children with macrocephaly: A prevalence study and PTEN gene analysis

Head circumference growth in children with Autism Spectrum Disorder: trend and clinical correlates in the first five years of life

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