Topic
Macrocephaly
About: Macrocephaly is a research topic. Over the lifetime, 1423 publications have been published within this topic receiving 35986 citations. The topic is also known as: (Macroencephaly) or (megalencephaly) or (enlarged brain) or (macrocephaly) & Cole-Hughes syndrome.
Papers published on a yearly basis
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Papers
TL;DR: Mutational analysis of PTEN in CD kindreds has identified germline mutations that are predicted to disrupt the protein tyrosine/dual-specificity phosphatase domain of this gene, and implies that PTEN may play a role in organizing the relationship of different cell types within an organ during development.
Abstract: Cowden disease (CD) is an autosomal dominant cancer predisposition syndrome associated with an elevated risk for tumours of the breast, thyroid and skin1–2. Lhermitte-Duclos disease (LDD) cosegregates with a subset of CD families and is associated with macrocephaly, ataxia and dysplastic cerebellar gangliocytomatosis3–4. The common feature of these diseases is a predisposition to hamartomas, benign tumours containing differentiated but disorganized cells indigenous to the tissue of origin. Linkage analysis has determined that a single locus within chromosome 10q23 is likely to be responsible for both of these diseases5. A candidate tumour suppressor gene (PTEN) within this region is mutated in sporadic brain, breast and prostate cancer6. Another group has independently isolated the same gene, termed MMAC1, and also found somatic mutations throughout the gene in advanced sporadic cancers7. Mutational analysis of PTEN in CD kindreds has identified germline mutations in four of five families. We found nonsense and missense mutations that are predicted to disrupt the protein tyrosine/dual-specificity phosphatase domain of this gene. Thus, PTEN appears to behave as a tumour suppressor gene in the germline. Our data also imply that PTEN may play a role in organizing the relationship of different cell types within an organ during development.
2,148 citations
TL;DR: The data suggest that abnormal activation of the PI3K/AKT pathway in specific neuronal populations can underlie macrocephaly and behavioral abnormalities reminiscent of certain features of human ASD.
1,007 citations
TL;DR: It is suggested that PTEN gene testing be considered for patients with autistic behaviour and extreme macrocephaly, and the gene findings may impact on recurrence risks as well as medical management for the patient.
Abstract: The genetic aetiology of autism remains elusive. Occasionally, individuals with Cowden syndrome (a cancer syndrome) and other related hamartoma disorders such as Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like conditions, are characterised by germline PTEN mutations, and may have neurobehavioural features resembling autism as well as overgrowth and macrocephaly. Therefore, we undertook PTEN gene mutation analysis in 18 subjects mainly prospectively ascertained with autism spectrum disorder and macrocephaly. Of these 18 autistic subjects (13 males and five females; ages 3.1–18.4 years) with a head circumference range from 2.5 to 8.0 standard deviations above the mean, three males (17%) carried germline PTEN mutations. These three probands had previously undescribed PTEN mutations: H93R (exon 4), D252G (exon 7), and F241S (exon 7). They had the larger head circumference measurements amongst all our study subjects. The three residues altered in our patients were highly evolutionarily conserved. We suggest that PTEN gene testing be considered for patients with autistic behaviour and extreme macrocephaly. The gene findings may impact on recurrence risks as well as medical management for the patient.
811 citations
TL;DR: The mTOR/PI3K pathway is associated with abnormal cellular/synaptic growth rate, whereas the NRXN-NLGN-SHANK pathways are associated with synaptogenesis and imbalance between excitatory and inhibitory currents.
690 citations
Baylor College of Medicine1, University of Illinois at Chicago2, University of Texas Health Science Center at San Antonio3, St. Joseph's Hospital and Medical Center4, University of Rochester5, University of California, San Francisco6, Washington University in St. Louis7, Eastern Maine Medical Center8, University of Michigan9, University of Connecticut10, Boston Children's Hospital11, Oklahoma State University–Stillwater12, University of Toronto13, University of Arkansas for Medical Sciences14
TL;DR: It is proposed that recurrent reciprocal microdeletions and microduplications within 1q21.1 represent previously unknown genomic disorders characterized by abnormal head size along with a spectrum of developmental delay, neuropsychiatric abnormalities, dysmorphic features and congenital anomalies.
Abstract: Chromosome region 1q21.1 contains extensive and complex low-copy repeats, and copy number variants (CNVs) in this region have recently been reported in association with congenital heart defects, developmental delay, schizophrenia and related psychoses. We describe 21 probands with the 1q21.1 microdeletion and 15 probands with the 1q21.1 microduplication. These CNVs were inherited in most of the cases in which parental studies were available. Consistent and statistically significant features of microcephaly and macrocephaly were found in individuals with microdeletion and microduplication, respectively. Notably, a paralog of the HYDIN gene located on 16q22.2 and implicated in autosomal recessive hydrocephalus was inserted into the 1q21.1 region during the evolution of Homo sapiens; we found this locus to be deleted or duplicated in the individuals we studied, making it a probable candidate for the head size abnormalities observed. We propose that recurrent reciprocal microdeletions and microduplications within 1q21.1 represent previously unknown genomic disorders characterized by abnormal head size along with a spectrum of developmental delay, neuropsychiatric abnormalities, dysmorphic features and congenital anomalies. These phenotypes are subject to incomplete penetrance and variable expressivity.
615 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 22 |
| 2024 | 36 |
| 2023 | 69 |
| 2022 | 132 |
| 2021 | 73 |
| 2020 | 83 |