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Results for “Neurodevelopmental Disorders”

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PubMed1996

Psychosocial adjustment and educational outcome in adolescents with a childhood diagnosis of attention deficit disorder.

OBJECTIVE: To conduct a retrospective follow-up study of psychosocial adjustment and educational outcome in adolescents with a childhood diagnosis of attention deficit disorder (ADD) and a group of clinical controls. METHODS: Groups included male and female subjects aged 14 to 18 years at time of follow-up with childhood diagnosis of ADD (cases; n = 48) versus other neurodevelopmental disorders (clinical controls; n = 37). Cases were also subdivided based on the presence of conduct disorder (CD) at follow-up. All groups were compared on measures of academic performance, self-esteem, behavior, alcohol and substance use, and adaptive functioning. RESULTS: Cases had significantly lower academic performance and poorer social, emotional, and adaptive functioning than clinical controls. Cases with CD had significantly lower academic performance, greater externalizing behaviors and emotional difficulties, and lower adaptive functioning than cases without CD. Cases with CD fared worse than clinical controls on self-report measures of behavior, socialization skills, and alcohol and substance use. CONCLUSIONS: These academic and psychosocial problems in adolescents with a childhood diagnosis of ADD suggest potential long-term ramifications for vocational and psychological functioning into adulthood. In addition, the presence of CD in some of these cases during adolescence appears to further increase the risk for maladaptive outcome.

Achievement↗

PubMed2006

Screening for MECP2 mutations in Spanish patients with an unexplained mental retardation.

Rett syndrome (RTT) is an X-linked progressive encephalopathy. Mutations in the MECP2 (methyl-CpG-binding protein) gene have been found to cause RTT. In the past few years, the role of MECP2 mutations in patients with mental disorders other than RTT has been studied, finding that mutations in MECP2 also contribute to non-syndromic entities. More recently, it has been demonstrated that RTT shares clinical features with those of Angelman syndrome, another neurodevelopmental disorder. These observations must be confirmed in a large series, to better understand the criteria needed for justifying a molecular test. Consequently, we have searched for MECP2 mutations in 294 patients (43 Angelman and Prader-Willi like included) with mental retardation (MR) of unknown aetiology. We found six polymorphisms (three novel, three previously reported) in 10 patients, one novel unclassified silent change (p.V222V) in a man, and one causative mutation in a girl with MR. Once this case was clinically reviewed, the girl presented symptoms of atypical RTT. The mutation (p.Y141C) lies within the methyl-binding domain, and has only been reported once in another atypical RTT. Our results show that the MECP2 mutations account for a low frequency (1/416 chromosomes = 0.24%) among mentally retarded individuals, which imply that it is necessary to perform an exhaustive clinical examination of patients before determining whether analysis of MECP2 is required or not.

Angelman Syndrome↗

PubMed2000

Preschoolers classified as having attention-deficit hyperactivity disorder (ADHD): DSM-IV symptom endorsement pattern.

In the present study, 50 preschoolers were formally and independently classified using both the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and third edition-revised (DSM-III-R) criteria for attention-deficit hyperactivity disorder (ADHD). The sample consisted of 25 preschoolers classified as having ADHD and 25 typically developing preschoolers for comparison; the sample was matched on gender, age, and socioeconomic status. All 50 preschoolers were without neurologic or neurodevelopmental disorders, oppositional defiant disorder, or language delay. There were four key findings: first, of the 25 preschoolers with ADHD, DSM-IV classification was as follows: hyperactive-impulsivity type (68%), combined type (28%), and inattentive type (4%). Second, the DSM-IV profiles showed that several symptoms were either infrequently endorsed by parents, reflecting limited applicability to preschoolers with ADHD, or frequently endorsed by parents of typically developing preschoolers, thus reducing their diagnostic value. Third, of the 25 preschoolers classified as having ADHD using DSM-IV criteria, 16% would not have been classified as having ADHD using the DSM-III-R criteria. The DSM-IV criteria therefore appear to be more lenient than the DSM-III-R criteria for this age group. Fourth, two symptoms that were not included in the DSM-IV, but were part of the DSM-III-R, were found to have clinical value for differentiating preschoolers with ADHD from their typically developing peers.

Attention↗

PubMed2006

Fetal alcohol spectrum disorders in Finland: clinical delineation of 77 older children and adolescents.

The adverse effects of alcohol on the developing human comprise a spectrum of structural anomalies and behavioral and neurocognitive disabilities, most accurately termed fetal alcohol spectrum disorders (FASD). We previously have proposed revisions to the 1996 Institute of Medicine Diagnostic Criteria for diagnoses in the FASD continuum [fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (PFAS), alcohol related birth defects (ARBD), and alcohol related neurodevelopmental disorder (ARND)], allowing for more reproducible and accurate FASD diagnosis in a clinical setting [Hoyme et al., 2005]. The NIAAA recently has coordinated and funded an international consortium of projects aimed at more complete characterization of the teratogenic spectrum of alcohol. One of the projects sites is in Finland. The aims of this project are: (1) to completely clinically characterize the structural and learning/behavioral phenotypes of a large cohort of older children and adolescents with moderate to severe disability within the FASD continuum; (2) to correlate FASD dysmorphology and behavioral phenotypes with CNS structure and function (i.e., MRS, MRI correlations); (3) to compare the phenotype of a genetically homogeneous population of Finnish children with FASD to that observed in other populations. We have recently completed dysmorphology examination and parent/guardian interviews of the 77 children in the Finnish cohort. The purpose of this report is to present historical and morphometric data on these patients, thereby more completely delineating the clinical spectrum of FASD in older children and adolescents, contrasting the phenotype with that described in other populations and examining whether a weighted dysmorphology score could be used as a clinical and research adjunct when fetal alcohol exposure is being suspected. All children were previously diagnosed with FASD by an experienced pediatric specialist in Finland, and all were exposed to significant maternal alcohol abuse prenatally. The sex ratio of the cohort was 0.38 (male: female) and ages ranged from 8 to 20 years, with a mean of 13 years. After application of the Revised IOM Diagnostic Criteria, 53% of the subjects were diagnosed as having FAS, 30% PFAS, 12% ARND, and 5% other diagnoses. Of note, although a family history of mental retardation or birth defects was rare, 43% of the children had one or more sibling who also carried a diagnosis of FAS. Eighty-nine percent of the mothers smoked cigarettes during gestation; other teratogenic exposures were rare. Almost none had undergone genetics evaluation in the past. Almost all of the subjects had resided in multiple foster placements since early childhood and had been followed regularly by pediatric specialists. Although 11% were born prematurely, 70% demonstrated prenatal growth deficiency, and 45% were microcephalic. Other than growth deficits and the cardinal facial features, the most common major and minor anomalies noted were: camptodactyly (55%), "hockey stick" or other altered palmar creases (51%), refractive errors (40%), strabismus (38%), dental crowding (43%), nail hypoplasia (38%), GU anomalies (22%), and congenital heart defects (18%), "Railroad track" ears were not observed in this population.

Abnormalities, Multiple↗

PubMed2005

Alcohol consumption in pregnant, black women is associated with decreased plasma and erythrocyte docosahexaenoic acid.

BACKGROUND: Inner-city, black women are among those groups that are at higher risk for having infants with fetal alcohol spectrum disorders that can include life-long neurobehavioral and cognitive impairments. Chronic alcohol consumption can decrease amounts of docosahexaenoic acid (DHA), a fatty acid that is essential for optimal infant neural and retinal development in a variety of tissues. METHODS: Black women who presented at an inner-city antenatal clinic for their first prenatal visit were recruited into a longitudinal, observational study. Alcohol intake was determined by a structured interview. Participants provided blood specimens and completed food frequency surveys at 24 weeks of gestation, infant delivery, and 3 months postpartum. Fatty acid composition analyses were completed on 307, 260, and 243 for plasma and 278, 261, and 242 erythrocyte specimens at 24 weeks of gestation, delivery, and 3 months postpartum, respectively. RESULTS: Proportion of drinking days at the first prenatal visit was associated with decreased DHA in plasma and erythrocytes throughout the study. This association was the strongest at 24 weeks of gestation. In addition, an interaction between proportion of drinking days at the time of conception and ounces of absolute alcohol per drinking day at the time of conception was detected and demonstrated that, in daily drinkers, high intakes of alcohol are associated with decreased DHA and arachidonic acid (AA) concentrations in plasma. CONCLUSIONS: Frequent and high intakes of alcohol that have been previously associated with fetal alcohol spectrum disorders are also associated with decreased maternal DHA and AA plasma concentrations. The present findings indicate that maternal DHA deficiency is associated with high-risk drinking and may contribute to the mechanism(s) of alcohol-related neurodevelopmental disorders.

Adult↗

PubMed2005

The neurodevelopmental model of schizophrenia: update 2005.

Neurodevelopmental models of schizophrenia that identify longitudinal precursors of illness have been of great heuristic importance focusing most etiologic research over the past two decades. These models have varied considerably with respect to specificity and timing of hypothesized genetic and environmental 'hits', but have largely focused on insults to prenatal brain development. With heritability around 80%, nongenetic factors impairing development must also be part of the model, and any model must also account for the wide range of age of onset. In recent years, longitudinal brain imaging studies of both early and adult (to distinguish from late ie elderly) onset populations indicate that progressive brain changes are more dynamic than previously thought, with gray matter volume loss particularly striking in adolescence and appearing to be an exaggeration of the normal developmental pattern. This supports an extended time period of abnormal neurodevelopment in schizophrenia in addition to earlier 'lesions'. Many subtle cognitive, motor, and behavioral deviations are seen years before illness onset, and these are more prominent in early onset cases. Moreover, schizophrenia susceptibility genes and chromosomal abnormalities, particularly as examined for early onset populations (ie GAD1, 22q11DS), are associated with premorbid neurodevelopmental abnormalities. Several candidate genes for schizophrenia (eg dysbindin) are associated with lower cognitive abilities in both schizophrenic and other pediatric populations more generally. Postmortem human brain and developmental animal studies document multiple and diverse effects of developmental genes (including schizophrenia susceptibility genes), at sequential stages of brain development. These may underlie the broad array of premorbid cognitive and behavioral abnormalities seen in schizophrenia, and neurodevelopmental disorders more generally. Increased specificity for the most relevant environmental risk factors such as exposure to prenatal infection, and their interaction with susceptibility genes and/or action through phase-specific altered gene expression now both strengthen and modify the neurodevelopmental theory of schizophrenia.

Adult↗

PubMed2001

Paternal factors and schizophrenia risk: de novo mutations and imprinting.

There is a strong genetic component for schizophrenia risk, but it is unclear how the illness is maintained in the population given the significantly reduced fertility of those with the disorder. One possibility is that new mutations occur in schizophrenia vulnerability genes. If so, then those with schizophrenia may have older fathers, because advancing paternal age is the major source of new mutations in humans. This review describes several neurodevelopmental disorders that have been associated with de novo mutations in the paternal germ line and reviews data linking increased schizophrenia risk with older fathers. Several genetic mechanisms that could explain this association are proposed, including paternal germ line mutations, trinucleotide repeat expansions, and alterations in genetic imprinting in one or several genes involved in neurodevelopment. Animal models may be useful in exploring these and other explanations for the paternal age effect and they may provide a novel approach for gene identification. Finally, it is proposed that environmental exposures of the father, as well as those of the mother and developing fetus, may be relevant to the etiology of schizophrenia.

Fathers↗

PubMed2026

A Case Report of Infantile Dopa-Responsive Dystonia Onset With Sleep Disorder Complicated With Autism Spectrum Disorder.

AIMS/BACKGROUND: Dopa-responsive dystonia (DRD) is a rare genetic disorder with complex and diverse clinical manifestations, resulting in a high rate of misdiagnosis. This case report describes an infantile case of DRD complicated by autism spectrum disorder (ASD), initially presenting with a sleep disorder. We aim to summarize its clinical manifestations, diagnostic process, treatment, and follow-up outcomes in order to improve clinical understanding of this disease. CASE PRESENTATION: A retrospective analysis was performed on a male infant who was treated at Jinhua Maternal and Child Health Care Hospital in 2020. The patient presented at one month of age with sleep disturbances, delayed motor development, and intermittent upward deviation of the eyes. Genetic testing identified two heterozygous pathogenic variants in the tyrosine hydroxylase (TH) gene. Among them, the c.738-2A>G variant was not recorded in the Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD), or 1000 Genomes Asian population databases. During follow-up, the patient was also found to have comorbid ASD. RESULTS: Genetic testing confirmed biallelic TH mutations, establishing the diagnosis of infantile DRD. The patient exhibited marked clinical response to levodopa/benserazide, though dose titration was required with growth. CONCLUSION: For infants with unexplained sleep disorder accompanied by delayed motor development, genetic testing should be performed as early as possible to facilitate the identification of the root cause and implement timely treatment. In addition, close follow-up should be conducted to detect comorbid neurodevelopmental disorders.

Humans↗

PubMed2005

Clinical manifestations and molecular investigation of 50 patients with Williams syndrome in the Greek population.

Williams syndrome (WS) is a well-recognized neurodevelopmental disorder manifested by both connective tissue and CNS abnormalities. The study depicts the 8-y experience and follow-up of 50 Greek children with the clinical diagnosis of WS. Clinical data on the facial features and cardiovascular, endocrinologic, and neurodevelopmental evaluation are presented. The most consistent findings were dysmorphic features (100%), followed by dental anomalies (90%) and hyperacousis (90%). Only eight of 50 children had severe cardiovascular defects that required surgical intervention during the first year of life. Supravalvular aortic stenosis was less frequent (28%) than shown in the literature. Severe hypertension was noticed in 22% of our patients, and infantile hypercalcemia was noticed in 6%. Twelve percent of our patients showed an elevation of CPK. Most children presented with moderate to severe mental retardation with IQ ranging from 20 to 85. Elastin hemizygosity was detected by fluorescence in situ hybridization. Dinucleotide repeat polymorphism analysis was performed in an attempt to correlate phenotype with genotype. The origin of deletions was more frequently maternal (59%), and a more severe phenotype seemed to be associated with those deletions. This is the first report on WS patients in the Greek population.

Adolescent↗

PubMed2025

Identification of a novel non-coding deletion in Allan-Herndon-Dudley syndrome by long-read HiFi genome sequencing.

BACKGROUND: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked disorder caused by pathogenic variants in the SLC16A2 gene. Although most reported variants are found in protein-coding regions or adjacent junctions, structural variations (SVs) within non-coding regions have not been previously reported. METHODS: We investigated two male siblings with severe neurodevelopmental disorders and spasticity, who had remained undiagnosed for over a decade and were negative from exome sequencing, utilizing long-read HiFi genome sequencing. We conducted a comprehensive analysis including short-tandem repeats (STRs) and SVs to identify the genetic cause in this familial case. RESULTS: While coding variant and STR analyses yielded negative results, SV analysis revealed a novel hemizygous deletion in intron 1 of the SLC16A2 gene (chrX:74,460,691 - 74,463,566; 2,876 bp), inherited from their carrier mother and shared by the siblings. Determination of the breakpoints indicates that the deletion probably resulted from Alu/Alu-mediated rearrangements between homologous AluY pairs. The deleted region is predicted to include multiple transcription factor binding sites, such as Stat2, Zic1, Zic2, and FOXD3, which are crucial for the neurodevelopmental process, as well as a regulatory element including an eQTL (rs1263181) that is implicated in the tissue-specific regulation of SLC16A2 expression, notably in skeletal muscle and thyroid tissues. CONCLUSIONS: This report, to our knowledge, is the first to describe a non-coding deletion associated with AHDS, demonstrating the potential utility of long-read sequencing for undiagnosed patients. Although interpreting variants in non-coding regions remains challenging, our study highlights this region as a high priority for future investigation and functional studies.

Humans↗

PubMed2003

Williams-Beuren syndrome: a challenge for genotype-phenotype correlations.

Many human chromosomal abnormality syndromes include specific cognitive and behavioural components. Children with Prader-Willi syndrome lack a paternally derived copy of the proximal long arm of chromosome 15, and eat uncontrollably; in Angelman syndrome lack of a maternal contribution of 15q11-q13 results in absence of speech, frequent smiling and episodes of paroxysmal laughter; deletions on 22q11 can be associated with obsessive behaviour and schizophrenia. The neurodevelopmental disorder Williams-Beuren syndrome (WBS), is caused by a microdeletion at 7q11.23 and provides us with one of the most convincing models of a relationship that links genes with human cognition and behaviour. The hypothesis is that deletion of one or a series of genes causes neurodevelopmental abnormalities that manifest as the fractionation of mental abilities typical of WBS. Detailed molecular characterization of the deletion alongside well-defined cognitive profiling in WBS provides a unique opportunity to investigate the neuromolecular basis of complex cognitive behaviour, and develop integrated approaches to study gene function and genotype-phenotype correlations.

Animals↗

PubMed1994

Research on neuropsychiatric genetics: interests of the National Institute of Neurological Disorders and Stroke.

The National Institute of Neurological Disorders and Stroke (NINDS) supports research concerning the determinants of normal and pathological development of the nervous system, from the genetic to the environmental. NINDS also funds basic and clinical research concerning the etiology, diagnosis, treatment, consequences, and prevention of the spectrum of neurodevelopmental disorders including neurobehavioral and neurodegenerative disorders (National Advisory Council Neurological Disorders and Stroke, 1989, 1992; Division of Convulsive, Developmental and Neuromuscular Disorders, NINDS, 1993).

Brain↗

PubMed2002

Missense mutations in the extracellular domain of the human neural cell adhesion molecule L1 reduce neurite outgrowth of murine cerebellar neurons.

Mutations in L1CAM, the gene encoding the transmembrane multifunctional neuronal adhesion molecule L1, are associated with neurodevelopmental disorders including X-linked hydrocephalus and mental retardation. Some amino acid substitutions in various extracellular domains of L1 are known to affect posttranslational processing of the protein or its homophilic and heterophilic interactions. It is largely unknown, however, how these mutations result in neurodevelopmental disturbances and whether the effects of mutations on neurodevelopment can be modeled in vitro. We stably expressed full-length human wild type L1 and the known pathogenic missense mutations I179S, R184W, Y194C, and C264Y in NIH-3T3 cells. L1 protein synthesis, glycosylation pattern, and subcellular localization were analyzed. Neurite outgrowth of primary murine cerebellar neurons was measured after 23 hrs of co-cultivation using transfected NIH-3T3 cells as substrate. Like wild type L1, L1 protein with I179S or Y194C mutations was localized on the surface of the transfected substrate cells, but this was not the case with R184W or C264Y mutations. All four mutations were associated with reduced stimulation of neurite outgrowth. Measurement of neurite outgrowth on transfected substrate cells may be a suitable model for studying neurodevelopmental disturbances.

3T3 Cells↗

PubMed2006

Hershey Medical Center Technical Workshop Report: optimizing the design and interpretation of epidemiologic studies for assessing neurodevelopmental effects from in utero chemical exposure.

Neurodevelopmental disabilities affect 3-8% of the 4 million babies born each year in the U.S. alone, with known etiology for less than 25% of those disabilities. Numerous investigations have sought to determine the role of environmental exposures in the etiology of a variety of human neurodevelopmental disorders (e.g., learning disabilities, attention deficit-hyperactivity disorder, intellectual disabilities) that are manifested in childhood, adolescence, and young adulthood. A comprehensive critical examination and discussion of the various methodologies commonly used in investigations is needed. The Hershey Medical Center Technical Workshop: Optimizing the design and interpretation of epidemiologic studies for assessing neurodevelopmental effects from in utero chemical exposure provided such a forum for examining these methodologies. The objective of the Workshop was to develop scientific consensus on the key principles and considerations for optimizing the design and interpretation of epidemiologic studies of in utero exposure to environmental chemicals and subsequent neurodevelopmental effects. (The Panel recognized that the nervous system develops post-natally and that critical periods of exposure can span several developmental life stages.) Discussions from the Workshop Panel generated 17 summary points representing key tenets of work in this field. These points stressed the importance of: a well-defined, biologically plausible hypothesis as the foundation of in utero studies for assessing neurodevelopmental outcomes; understanding of the exposure to the environmental chemical(s) of interest, underlying mechanisms of toxicity, and anticipated outcomes; the use of a prospective, longitudinal cohort design that, when possible, runs for periods of 2-5 years, and possibly even longer, in an effort to assess functions at key developmental epochs; measuring potentially confounding variables at regular, fixed time intervals; including measures of specific cognitive and social-emotional domains along with non-cognitive competence in young children, as well as comprehensive measures of health; consistency of research design protocols across studies (i.e., tests, covariates, and analysis styles) in an effort to improve interstudy comparisons; emphasis on design features that minimize introduction of systematic error at all stages of investigation: participant selection, data collection and analysis, and interpretation of results; these would include (but not be limited to) reducing selection bias, using double-blind designs, and avoiding post hoc formulation of hypotheses; a priori data analysis strategies tied to hypotheses and the overall research design, particularly for methods used to characterize and address confounders in any neurodevelopmental study; actual quantitative measurements of exposure, even if indirect, rather than methods based on subject recall; careful examination of standard test batteries to ensure that the battery is tailored to the age group as well as what is known about the specific neurotoxic effects on the developing nervous system; establishment of a system for neurodevelopmental surveillance for tracking the outcomes from in utero exposure across early developmental time periods to determine whether central nervous system injuries may be lying silent until developmentally challenged; ongoing exploration of computerized measures that are culturally and linguistically sensitive, and span the age range from birth into the adolescent years; routine incorporation of narrative in manuscripts concerning the possibility of spurious (i.e., false positive and false negative) test results in all research reportage (this can be facilitated by detailed, transparent reporting of design, covariates, and analyses so that others can attempt to replicate the study); forthright, disciplined, and intellectually honest treatment of the extent to which results of any study are conclusive--that is, how generalizable the results of the study are in terms of the implications for the individual study participants, the community studied, and human health overall; confinement of reporting to the actual research questions, how they were tested, and what the study found, and avoiding, or at least keeping to a minimum, any opinions or speculation concerning public health implications; education of clinicians and policymakers to critically read scientific reports, and to interpret study findings and conclusions appropriately; and recognition by investigators of their ethical duty to report negative as well as positive findings, and the importance of neither minimizing nor exaggerating these findings.

Biomedical Research↗

PubMed2025

A Massively Parallel CRISPR-Based Screening Platform for Modifiers of Neuronal Activity.

Understanding the complex interplay between gene expression and neuronal activity is crucial for unraveling the molecular mechanisms underlying cognitive function and neurological disorders. Here, we developed pooled screens for neuronal activity, using CRISPR interference (CRISPRi) and the fluorescent calcium integrator CaMPARI2. Using this screening method, we evaluated 1343 genes for their effect on excitability in human iPSC-derived neurons, revealing potential links to neurodegenerative and neurodevelopmental disorders. These genes include known regulators of neuronal excitability, such as TARPs and ion channels, as well as genes associated with autism spectrum disorder and Alzheimer's disease not previously described to affect neuronal excitability. This CRISPRi-based screening platform offers a versatile tool to uncover molecular mechanisms controlling neuronal activity in health and disease.

Journal Article↗

PubMed2004

Nutrients, neurodevelopment, and mood.

Human neurodevelopment is the result of genetic and environmental interactions. This paper examines the role of prenatal nutrition relative to psychiatric disorders and explores the relationship among nutrients, mood changes, and mood disorders. Epidemiologic studies have found that adults who were born with a normal, yet low birth weight have an increased susceptibility to diseases such as coronary heart disease, diabetes, and stroke in adulthood. Prenatal caloric malnutrition, low birth weight, and prematurity also increase the risk for neurodevelopmental disorders, schizophrenia, affective disorders, and schizoid and antisocial personality disorders. Placebo-controlled studies in medicated patients suggest that add-on treatment with omega-3 fatty acids, particularly eicosapentaenoic acid, may ameliorate symptoms of major depressive disorder. Additional studies are necessary to confirm any benefits for bipolar disorders.

Adult↗

PubMed2003

A3243G mitochondrial mutation associated with polymicrogyria.

The mitochondrial transfer ribonucleic acid for leucine is encoded by nucleotides 3230-3304. A-to-G transition at nucleotide 3243 can cause maternally transmitted diabetes mellitus-deafness syndrome, and MELAS syndrome. MELAS syndrome is a rare disorder of mitochondrial energy production, and is an acronym for myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. Cortical malformations are heterogeneous and result from abnormal cell proliferation/apoptosis, migration, and/or differentiation of neuroepithelial cells. They are an important and relatively common cause of intractable epilepsy and neurodevelopmental disorders. The association between these A3243G mutations and cortical malformation has never before been reported. Here a 14-year-old female with A3243G mutation and polymicrogyria is described and possible aetiologies of this association are discussed.

Adolescent↗

PubMed2000

Williams syndrome and related disorders.

Three clinical conditions displaying phenotypic overlap have been linked to mutation or deletion of the elastin gene at 7q11.23. Supravalvar aortic stenosis, an autosomal dominant disorder characterized by elastin arteriopathy, is caused by mutation or intragenic deletions of ELN resulting in loss of function. Autosomal dominant cutis laxa, a primarily cutaneous condition, is the result of frameshift mutations at ELN that cause a dominant-negative effect on elastic fiber structure. Williams syndrome, a neurodevelopmental disorder is due to a 1.5 Mb deletion that includes ELN and at least 15 contiguous genes. The disorder is characterized by dysmorphic facies, mental retardation or learning difficulties, elastin arteriopathy, a unique cognitive profile of relative strength in auditory rote memory and language and extreme weakness in visuospatial constructive cognition, and a typical personality that includes overfriendliness, anxiety, and attention problems. The understanding of these disorders has progressed from phenotypic description to identification of causative mutations and insight into pathogenetic mechanisms for some aspects of the phenotype.

Aortic Stenosis, Supravalvular↗