-
Genetics in Medicine : Official Journal... Apr 2013Rare, recurrent chromosome 1q21.1 duplications have been associated with developmental delay, congenital anomalies, and macrocephaly in children. Data on adult clinical... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Rare, recurrent chromosome 1q21.1 duplications have been associated with developmental delay, congenital anomalies, and macrocephaly in children. Data on adult clinical expression would help to inform genetic counseling.
METHODS
A systematic review of 22 studies reporting 107 individuals (59 children and 48 adults) with 1q21.1 duplications was conducted. We compiled the available phenotypic data to attempt to identify the most highly associated clinical features and to determine expression in adults. We also report on seven adult cases newly identified in the studies of schizophrenia and tetralogy of Fallot at our center.
RESULTS
Five cases were ascertained as controls, 32 as relatives of probands, and 70 as having clinical features: autism spectrum disorder (n = 15), congenital heart disease (n = 12), schizophrenia (n = 10), or other, mostly developmental, features (n = 33). The 1q21.1 duplication was significantly enriched in the cohorts with schizophrenia (P = 0.0155) and tetralogy of Fallot (P = 0.0040) at our center as compared with controls. There was a paucity of clinical data for adults; the most common features, other than those used for ascertainment, included macrocephaly and abnormalities of possible connective tissue origin (e.g., carpal tunnel syndrome).
CONCLUSION
Further data are needed to characterize lifetime expression of 1q21.1 duplications. These initial results, however, suggest that anticipatory care should include attention to later-onset conditions such as schizophrenia.
Topics: Adolescent; Adult; Anticipation, Genetic; Child; Child, Preschool; Chromosome Duplication; Chromosomes, Human, Pair 1; Female; Genetic Counseling; Humans; Infant; Male; Middle Aged; Phenotype
PubMed: 23018752
DOI: 10.1038/gim.2012.129 -
Journal of Neurodevelopmental Disorders Jan 2022Phosphatase and tensin homologue (PTEN) is a cancer suppressor gene. Constitutional mutations affecting this gene are associated with several conditions, collectively... (Meta-Analysis)
Meta-Analysis Review
Behavioural and psychological features of PTEN mutations: a systematic review of the literature and meta-analysis of the prevalence of autism spectrum disorder characteristics.
BACKGROUND
Phosphatase and tensin homologue (PTEN) is a cancer suppressor gene. Constitutional mutations affecting this gene are associated with several conditions, collectively termed PTEN hamartoma tumour syndromes (PHTS). In addition to hamartomas, PTEN aberrations have been associated with a range of non-tumoural phenotypes such as macrocephaly, and research indicates possibly increased rates of developmental delay and autism spectrum disorder (ASD) for people with germline mutations affecting PTEN.
METHOD
A systematic review of literature reporting behavioural and psychological variables for people with constitutional PTEN mutations/PHTS was conducted using four databases. Following in-depth screening, 25 articles met the inclusion criteria and were used in the review. Fourteen papers reported the proportion of people with PTEN mutations/PTHS meeting criteria for or having characteristics of ASD and were thus used in a pooled prevalence meta-analysis.
RESULTS
Meta-analysis using a random effects model estimated pooled prevalence of ASD characteristics at 25% (95% CI 16-33%), although this should be interpreted cautiously due to possible biases in existing literature. Intellectual disability and developmental delay (global, motor and speech and language) were also reported frequently. Emotional difficulties and impaired cognitive functioning in specific domains were noted but assessed/reported less frequently. Methods of assessment of psychological/behavioural factors varied widely (with retrospective examination of medical records common).
CONCLUSIONS
Existing research suggests approximately 25% of people with constitutional PTEN mutations may meet criteria for or have characteristics of ASD. Studies have also begun to establish a range of possible cognitive impairments in affected individuals, especially when ASD is also reported. However, further large-scale studies are needed to elucidate psychological/behavioural corollaries of this mutation, and how they may relate to physiological/physical characteristics.
Topics: Autism Spectrum Disorder; Germ-Line Mutation; Humans; Mutation; PTEN Phosphohydrolase; Prevalence; Retrospective Studies
PubMed: 34983360
DOI: 10.1186/s11689-021-09406-w -
Medical Journal of the Islamic Republic... 2019Autism Spectrum Disorder (ASD) is a neurological disorder characterized by massive damage in various fields of development. Impaired social interaction and...
Autism Spectrum Disorder (ASD) is a neurological disorder characterized by massive damage in various fields of development. Impaired social interaction and communication skills, unusual behavior or interests, and repetitive activities are considerably disabling in these patients. There are several challenges in diagnosis of ASD patients such as co-existing epilepsy, difference in clinician attitudes and possibly multifactorial etiology of autistic behavior among children and adults. Research in recent years has emphasized a possible connection between mutations in and macrocephaly (head circumference > 97th centile). Articles in English Language were searched from international databases including Medline (PubMed), Google Scholar, Scopus, and CINHAL from January 1998 to January 2016. The results showed that among 2940 patients with behavioral disorders, 2755 individuals had ASD, and 35 cases with macrocephaly had mutations in . About 77% of the articles (7/9) analyzed mutations in in patients with head circumference more than 2SD away from the mean, but did not check mutations in this gene in other ASD patients without macrocephaly. To the best of our knowledge, this study is the first systematic review on human mutations and classical autistic behavior. We conclude that the presence of macrocephaly may not be sufficient to examine the mutation in this group; however, surveying this gene in all cases of macrocephaly seems to be necessary.
PubMed: 31086789
DOI: 10.34171/mjiri.33.10 -
Autism : the International Journal of... Apr 2021Neurological disorders, such as epilepsy and cerebral palsy, have been reported to occur among individuals with autism beyond chance and may have an impact on daily... (Meta-Analysis)
Meta-Analysis
Neurological disorders, such as epilepsy and cerebral palsy, have been reported to occur among individuals with autism beyond chance and may have an impact on daily living across the lifespan. Although there has been research investigating neurological disorders in autism, the findings are not always conclusive. Previous summaries of existing studies have not evaluated the full range of neurological disorders. This study aimed to comprehensively explore the neurological problems appearing in autism to provide updated information that is needed for better healthcare and support in this population. We looked at already published studies focusing on risk or frequency of neurological disorders in autism. Our results suggest that individuals with autism are more likely than the general population to have a range of neurological disorders, including epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headache, and inborn abnormalities of the nervous system. In order to provide individualized healthcare and support of high quality to individuals diagnosed with autism, health care professionals and other support providers need to be attentive to neurological complications. To further improve our understanding about the link between autism and neurological disorders, future research should follow the neurological health of children who are diagnosed with or are at increased likelihood of autism.
Topics: Autism Spectrum Disorder; Autistic Disorder; Child; Epilepsy; Humans
PubMed: 32907344
DOI: 10.1177/1362361320951370 -
American Journal of Medical Genetics.... May 2010Costello syndrome is a rasopathy caused by germline mutations in the proto-oncogene HRAS. Its presentation includes failure-to-thrive with macrocephaly, characteristic... (Review)
Review
High incidence of progressive postnatal cerebellar enlargement in Costello syndrome: brain overgrowth associated with HRAS mutations as the likely cause of structural brain and spinal cord abnormalities.
Costello syndrome is a rasopathy caused by germline mutations in the proto-oncogene HRAS. Its presentation includes failure-to-thrive with macrocephaly, characteristic facial features, hypertrophic cardiomyopathy, papillomata, malignant tumors, and cognitive impairment. In a systematic review we found absolute or relative macrocephaly (100%), ventriculomegaly (50%), and other abnormalities on brain and spinal cord imaging studies in 27/28 individuals. Posterior fossa crowding with cerebellar tonsillar herniation (CBTH) was noted in 27/28 (96%), and in 10/17 (59%) with serial studies posterior fossa crowding progressed. Sequelae of posterior fossa crowding and CBTH included hydrocephalus requiring shunt or ventriculostomy (25%), Chiari 1 malformation (32%), and syrinx formation (25%). Our data reveal macrocephaly with progressive frontal bossing and CBTH, documenting an ongoing process rather than a static congenital anomaly. Comparison of images obtained in young infants to subsequent studies demonstrated postnatal development of posterior fossa crowding. This process of evolving megalencephaly and cerebellar enlargement is in keeping with mouse model data, delineating abnormal genesis of neurons and glia, resulting in an increased number of astrocytes and enlarged brain volume. In Costello syndrome and macrocephaly-capillary malformation syndrome disproportionate brain growth is the main factor resulting in postnatal CBTH and Chiari 1 malformation.
Topics: Cerebellum; Costello Syndrome; Humans; Incidence; Infant, Newborn; Mutation; Proto-Oncogene Mas; Proto-Oncogene Proteins p21(ras); Spinal Cord
PubMed: 20425820
DOI: 10.1002/ajmg.a.33391 -
Fetal Diagnosis and Therapy 2019Fetal subdural haematoma (SDH) is associated with poor prognosis.
BACKGROUND
Fetal subdural haematoma (SDH) is associated with poor prognosis.
OBJECTIVE
The conflicting evidence from the literature presents a challenge in prenatal counselling. We present a case study and systematic review of the literature for the management and outcome of fetal SDH.
METHODS
Systematic search of electronic database.
RESULTS
A total 45 cases were extracted from 39 papers. Prenatal ultrasonographic features were intracranial echogenicity (42%), lateral ventriculomegaly (38%), presence of an intracranial mass (31%), macrocephaly (24%), midline deviation of cerebral falx (20%), and intracranial fluid collection (11%). Further secondary features were noted including reversed diastolic flow in the middle cerebral artery (11%), echogenic bowel (4%), hydrops fetalis (2%), and elevated middle cerebral artery peak systolic velocity (2%) (all highly likely to be associated with fetal anaemia). The rates of termination of pregnancy, stillbirth, and neonatal death were 18% (8/45), 16% (7/45), and 11% (5/45), respectively. Overall, therefore, the fetal and perinatal mortality was 32% (12/37). Amongst the 24 survivors with available neurological outcome, 42% (10/24) and 58% (14/24) had abnormal and normal neurological outcome, respectively. Underlying aetiology of fetal SDH was not identified in 47% (21/45). Fetal SDH with an identifiable underlying aetiology was the only factor associated with a higher chance of normal neurological outcome when compared to fetal SDH without a detectable cause (78.5 vs. 21.4%, p = 0.035).
CONCLUSIONS
Stillbirth and neonatal death occurred in a significant proportion of fetal SDH. 58% of survivors had normal neurological outcome, and better prognosis was seen in SDH with identifiable underlying aetiology.
Topics: Adult; Fatal Outcome; Female; Fetal Membranes, Premature Rupture; Gestational Age; Hematoma, Subdural; Humans; Magnetic Resonance Imaging; Obstetric Labor, Premature; Predictive Value of Tests; Pregnancy; Risk Factors; Stillbirth; Ultrasonography, Prenatal
PubMed: 30861511
DOI: 10.1159/000496202 -
BMJ Open Jan 2014The World Health Organization (WHO) has established a set of growth curves for use as international standards in children up to age 5. The WHO's position is that all... (Comparative Study)
Comparative Study Review
OBJECTIVE
The World Health Organization (WHO) has established a set of growth curves for use as international standards in children up to age 5. The WHO's position is that all economically advantaged children who were breastfed as infants grow similarly. As a result, a single set of growth charts can be used to judge growth in any child, regardless of race or ethnicity. The goal of this study was to compare mean heights, weights and head circumferences from a variety of studies with the WHO's data.
DESIGN
We compared data from the WHO's Multicentre Growth Reference Study (MGRS) with data from studies performed in 55 countries or ethnic groups.
DATA SOURCES
PubMed, WHO Global Database on Child Growth and Malnutrition, SciELO, Google Scholar, Textbooks and Ministries of Statistics and Public Health.
ELIGIBILITY CRITERIA
Large recent studies (1988-2013) of economically advantaged groups, including comparisons with cohorts of breastfed children wherever possible.
RESULTS
Height varied somewhat among different national and ethnic groups. Means were generally within 0.5 of an SD of the MGRS means. Weight varied more than height, but the low MGRS means were seen as endorsing slenderness in the midst of an obesity epidemic. The mean head circumference varied widely. In many groups, means were consistently 0.5-1 SD above the MGRS mean. Head size in breastfed children at any age examined was far closer to local norms than to the MGRS means.
CONCLUSIONS
Height and weight curves may not be optimal fits in all cases. The differences between national or ethnic group head circumference means were large enough that using the WHO charts would put many children at risk for misdiagnosis of macrocephaly or microcephaly. Our findings indicate that the use of a single international standard for head circumference is not justified.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (# CRD42013003675).
Topics: Body Weight; Breast Feeding; Cephalometry; Child, Preschool; Female; Global Health; Growth Charts; Humans; Infant; Infant, Newborn; Male; World Health Organization
PubMed: 24401723
DOI: 10.1136/bmjopen-2013-003735 -
BMC Genomics Dec 2022Modern human brains and skull shapes differ from other hominids. Brain growth disorders as micro- (ASPM, MCPH1) and macrocephaly (NFIX, GLI3) have been highlighted as...
BACKGROUND
Modern human brains and skull shapes differ from other hominids. Brain growth disorders as micro- (ASPM, MCPH1) and macrocephaly (NFIX, GLI3) have been highlighted as relevant for the evolution in humans due to the impact in early brain development. Genes associated with macrocephaly have been reported to cause this change, for example NSD1 which causes Sotos syndrome.
RESULTS
In this study we performed a systematic literature review, located the reported variants associated to Sotos syndrome along the gene domains, compared the sequences with close primates, calculated their similarity, Ka/Ks ratios, nucleotide diversity and selection, and analyzed the sequence and structural conservation with distant primates. We aimed to understand if NSD1 in humans differs from other primates since the evolution of NSD1 has not been analyzed in primates, nor if the localization of the mutations is limited to humans. Our study found that most variations causing Sotos syndrome are in exon 19, 22 and 10. In the primate comparison we did not detect Ka/Ks ratios > 1, but a high nucleotide diversity with non-synonymous variations in exons 10, 5, 9, 11 and 23, and sites under episodic selection in exon 5 and 23, and human, macaque/colobus/tarsier/galago and tarsier/lemur/colobus. Most of the domains are conserved in distant primates with a particular progressive development from a simple PWWP1 in O. garnetti to a complex structure in Human.
CONCLUSION
NSD1 is a chromatin modifier that suggests that the selection could influence brain development during modern human evolution and is not present in other primates; however, nowadays the nucleotide diversity is associated with Sotos syndrome.
Topics: Humans; Animals; Sotos Syndrome; Histone Methyltransferases; Histone-Lysine N-Methyltransferase; Tarsiidae; Colobus; Nuclear Proteins; Mutation; Exons; Hominidae; Megalencephaly; Nucleotides; Cytoskeletal Proteins; Cell Cycle Proteins
PubMed: 36550402
DOI: 10.1186/s12864-022-09071-w